liraglutide/insulin degludec (Rx)

Brand and Other Names:Xultophy
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Dosing & Uses

AdultPediatricGeriatric

Dosage forms & Strengths

liraglutide/insulin degludec

SC injection

  • 3.6mg/100units per mL
  • Available as a 3-mL single-use pen

Type 2 Diabetes Mellitus

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

The pen delivers doses from 10-50 units with each injection

Each dosage unit contains 1 unit of insulin degludec and 0.036 mg of liraglutide

Use alternative antidiabetic products if patients require a daily dosage persistently below 16 units or over 50 units

Starting dose

  • Discontinue basal insulin or GLP-1 agonist before initiating liraglutide/insulin degludec
  • Patients who are naïve to basal insulin or GLP-1 agonists: insulin degludec 10 units/liraglutide 0.36 mg SC qDay
  • Patients currently on basal insulin or a GLP-1 agonist: insulin degludec 16 units/liraglutide 0.58 mg SC qDay

Dose titration

  • May titrate dose upwards or downwards by 2 units every 3-4 days based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal until the desired fasting plasma glucose is achieved
  • To minimize the risk of hypoglycemia or hyperglycemia, additional titration may be needed
    • Changes in physical activity, meal patterns (ie, macronutrient content or timing of food intake), or renal or hepatic function
    • During acute illness
    • When used with other medications

Dosage Modifications

Renal impairment

  • Severe (liraglutide/insulin degludec): Not studied
  • Liraglutide: Postmarketing reports in patients with severe renal impairment of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis

Hepatic impairment

  • Not studied

Dosing Considerations

Limitations of use

  • Not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rodent C-cell tumor findings to humans
  • Not recommended in combination with any other product containing liraglutide or another GLP-1 receptor agonist
  • Not indicated for type 1 diabetes mellitus or treatment of diabetic ketoacidosis
  • Has not been studied in combination with prandial insulin

Safety and efficacy not established

Initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions

Hypoglycemia may be more difficult to recognize in elderly individuals

Next:

Interactions

Interaction Checker

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              • ethanol

                ethanol, insulin degludec. Other (see comment). Avoid or Use Alternate Drug. Comment: Alcohol may either increase or decrease the blood glucose lowering effect of insulin; alcohol may decrease endogenous glucose production (increased hypoglycemia risk) or worsen glycemic control by adding calories.

              • macimorelin

                insulin degludec, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may transiently elevate growth hormone (GH) concentrations may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.

              Monitor Closely (229)

              • acarbose

                liraglutide, acarbose. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

                acarbose, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • acebutolol

                acebutolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • aripiprazole

                aripiprazole, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • albiglutide

                albiglutide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • alogliptin

                alogliptin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • aripiprazole

                aripiprazole decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • asenapine

                asenapine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

                asenapine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • aspirin

                aspirin increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

              • atazanavir

                atazanavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • atazanavir

                atazanavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • atenolol

                atenolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • atorvastatin

                liraglutide will decrease the level or effect of atorvastatin by Other (see comment). Use Caution/Monitor. Based on pharmacokinetic studies liraglutide decreased atorvastatin Cmax by 38% and median Tmax delayed from 1h to 3h with liraglutide and the AUC did not change.

              • azilsartan

                azilsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

                azilsartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                azilsartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              • bazedoxifene/conjugated estrogens

                bazedoxifene/conjugated estrogens decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • benazepril

                benazepril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypoglycemic effects; Monitor blood glucose.

              • benazepril

                benazepril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

              • bendroflumethiazide

                bendroflumethiazide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • betamethasone

                betamethasone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

                betamethasone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • betaxolol

                betaxolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • candesartan

                candesartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              • bisoprolol

                bisoprolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • bumetanide

                bumetanide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • canagliflozin

                canagliflozin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • candesartan

                candesartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                candesartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • captopril

                captopril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose. Monitor blood glucose.

                captopril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

              • cariprazine

                cariprazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • chlorothiazide

                chlorothiazide decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

              • carvedilol

                carvedilol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • chlorothiazide

                chlorothiazide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • chlorpromazine

                chlorpromazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

                chlorpromazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • chlorpropamide

                chlorpropamide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

                liraglutide, chlorpropamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

              • chlorthalidone

                chlorthalidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

                chlorthalidone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

              • chromium

                chromium, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • cinnamon

                cinnamon increases effects of liraglutide by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

              • clonidine

                clonidine, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.

              • clozapine

                clozapine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

                clozapine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • conjugated estrogens

                conjugated estrogens decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

                conjugated estrogens decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • conjugated estrogens, vaginal

                conjugated estrogens, vaginal decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • corticotropin

                corticotropin decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • cortisone

                cortisone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

                cortisone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • danazol

                danazol decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Danazol may cause insulin resistance.

              • darunavir

                darunavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • dapagliflozin

                dapagliflozin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • darunavir

                darunavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • deflazacort

                insulin degludec and deflazacort both decrease serum potassium. Use Caution/Monitor.

              • desogestrel

                desogestrel decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • dexamethasone

                dexamethasone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

                dexamethasone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • diazoxide

                diazoxide decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Diazoxide increases blood glucose by inhibiting pancreatic insulin release and stimulating catecholamines release.

              • drospirenone

                drospirenone decreases effects of liraglutide by passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • dichlorphenamide

                dichlorphenamide and insulin degludec both decrease serum potassium. Use Caution/Monitor.

              • dienogest/estradiol valerate

                dienogest/estradiol valerate decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens and progesterones may impair glucose tolerance.

              • disopyramide

                disopyramide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                disopyramide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and disopyramide may require insulin dosage adjustment and increased glucose monitoring.

              • droxidopa

                droxidopa decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • dulaglutide

                dulaglutide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • empagliflozin

                empagliflozin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

              • enalapril

                enalapril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                enalapril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

              • ephedrine

                ephedrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • eprosartan

                eprosartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              • epinephrine

                epinephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • eprosartan

                eprosartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                eprosartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • ertugliflozin

                ertugliflozin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.

              • erythromycin base

                erythromycin base, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • esmolol

                esmolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • estradiol

                estradiol decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

                estradiol decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estradiol may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • estradiol combos

                estradiol combos decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • estrogens conjugated synthetic

                estrogens conjugated synthetic decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • estrogens conjugated synthetic

                estrogens conjugated synthetic decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • estrogens esterified

                estrogens esterified decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • estropipate

                estropipate decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estropipate may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • ethacrynic acid

                ethacrynic acid decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • ethinylestradiol

                ethinylestradiol decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

                ethinylestradiol decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • etonogestrel

                etonogestrel decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Etonogestrel may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

                etonogestrel decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • exenatide injectable solution

                exenatide injectable solution, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • fludrocortisone

                fludrocortisone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

              • exenatide injectable suspension

                exenatide injectable suspension, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • fenofibrate

                fenofibrate, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • fenofibrate micronized

                fenofibrate micronized, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • fenofibric acid

                fenofibric acid, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • fludrocortisone

                fludrocortisone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • fluoxetine

                fluoxetine, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                fluoxetine increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and fluoxetine may require insulin dosage adjustment and increased glucose monitoring.

              • fluphenazine

                fluphenazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

                fluphenazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

              • fosamprenavir

                fosamprenavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

                fosamprenavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • fosinopril

                fosinopril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

                fosinopril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • furosemide

                furosemide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • glimepiride

                liraglutide, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

              • gemfibrozil

                gemfibrozil, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • glimepiride

                glimepiride, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • glipizide

                glipizide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

                liraglutide, glipizide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

              • glucagon

                glucagon decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Endogenous glucagon is a regulatory hormone that increases blood glucose levels; exogenous glucagon is often used to treat hypoglycemia in patients with diabetes mellitus.

              • glyburide

                liraglutide, glyburide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

              • glucagon intranasal

                glucagon intranasal decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Endogenous glucagon is a regulatory hormone that increases blood glucose levels; exogenous glucagon is often used to treat hypoglycemia in patients with diabetes mellitus.

              • glyburide

                glyburide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • hydrochlorothiazide

                hydrochlorothiazide decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

                hydrochlorothiazide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • hydrocortisone

                hydrocortisone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

                hydrocortisone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

              • hydroxyprogesterone caproate

                hydroxyprogesterone caproate decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • iloperidone

                iloperidone, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • iloperidone

                iloperidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • indapamide

                indapamide decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

                indapamide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • indinavir

                indinavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

                indinavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • insulin aspart

                liraglutide, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • irbesartan

                irbesartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                irbesartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • insulin aspart protamine/insulin aspart

                liraglutide, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin degludec

                liraglutide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin degludec/insulin aspart

                liraglutide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin detemir

                liraglutide, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin glargine

                liraglutide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin glulisine

                liraglutide, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin inhaled

                liraglutide, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin isophane human/insulin regular human

                liraglutide, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin lispro

                liraglutide, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin lispro protamine/insulin lispro

                liraglutide, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin NPH

                liraglutide, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin regular human

                liraglutide, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • irbesartan

                irbesartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              • isocarboxazid

                isocarboxazid, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • isoniazid

                isoniazid decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Isoniazid may increase blood glucose (rare).

              • labetalol

                labetalol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • lanreotide

                lanreotide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                lanreotide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.

              • levonorgestrel intrauterine

                levonorgestrel intrauterine decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • levonorgestrel oral

                levonorgestrel oral decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

                levonorgestrel oral decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • levothyroxine

                levothyroxine decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • lisinopril

                lisinopril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

              • linagliptin

                linagliptin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • liothyronine

                liothyronine decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • liotrix

                liotrix decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • liraglutide

                liraglutide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • lisinopril

                lisinopril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • lithium

                lithium, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Lithium may either increase or decrease the blood glucose lowering effect of antidiabetic agents.

                lithium, insulin degludec. unspecified interaction mechanism. Use Caution/Monitor. Lithium salts may cause either hypoglycemia or hyperglycemia. Insulin dosage adjustment and increased glucose monitoring may be required.

              • lixisenatide

                lixisenatide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypoglycemia increased when coadministered with basal insulins. Basal insulin dose reduction may be required.

              • lopinavir

                lopinavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • losartan

                losartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

                losartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                losartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              • lurasidone

                lurasidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

                lurasidone, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • magnesium salicylate

                magnesium salicylate increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

              • medroxyprogesterone

                medroxyprogesterone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Medroxyprogesterone may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • mecasermin

                mecasermin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • medroxyprogesterone

                medroxyprogesterone decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • megestrol

                megestrol decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • mestranol

                mestranol decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • metformin

                liraglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

                metformin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • methyclothiazide

                methyclothiazide decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

                methyclothiazide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • methylprednisolone

                methylprednisolone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

                methylprednisolone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

              • methyltestosterone

                methyltestosterone increases effects of liraglutide by pharmacodynamic synergism. Use Caution/Monitor. It is important to monitor all patients with type 2 diabetes on antidiabetic agents receiving androgens for changes in glycemic control. Potential for hypoglycemia.

              • metoclopramide intranasal

                metoclopramide intranasal increases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose. Monitor blood glucose and adjust insulin dosage regimen as needed.

              • metolazone

                metolazone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

                metolazone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • metoprolol

                metoprolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • miglitol

                liraglutide, miglitol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

              • miglitol

                miglitol, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • moexipril

                moexipril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                moexipril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

              • nadolol

                nadolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • nateglinide

                liraglutide, nateglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

              • nateglinide

                nateglinide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • nebivolol

                nebivolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • nelfinavir

                nelfinavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

                nelfinavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • niacin

                niacin decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant use of insulin and niacin may require insulin dosage adjustment and increased glucose monitoring.

              • norethindrone acetate

                norethindrone acetate decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • norepinephrine

                norepinephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • norethindrone

                norethindrone decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • norethindrone acetate

                norethindrone acetate decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • norethindrone transdermal

                norethindrone transdermal decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • norgestimate

                norgestimate decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              • octreotide

                octreotide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                octreotide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.

              • olanzapine

                olanzapine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

                olanzapine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • olmesartan

                olmesartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

                olmesartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

                olmesartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • paliperidone

                paliperidone, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

                paliperidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • pasireotide

                pasireotide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                pasireotide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.

              • pegvisomant

                pegvisomant increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Pegvisomant may increase glucose tolerance. Dosage reductions of antidiabetic agents may be needed to avoid potential hypoglycemia.

              • penbutolol

                penbutolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • pentamidine

                pentamidine, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Pentamidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

                pentamidine, insulin degludec. unspecified interaction mechanism. Use Caution/Monitor. Pentamidine may cause either hypoglycemia or hyperglycemia followed by the opposing effect. Insulin dosage adjustment and increased glucose monitoring may be required.

              • pentoxifylline

                pentoxifylline, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • perindopril

                perindopril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                perindopril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

              • perphenazine

                perphenazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

                perphenazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

              • phenelzine

                phenelzine, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • pioglitazone

                liraglutide, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

              • phenylephrine

                phenylephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • pindolol

                pindolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • pioglitazone

                pioglitazone, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • pramlintide

                liraglutide, pramlintide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

                pramlintide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Pramlintide is indicated to be used in combination with insulin; however, pamlintide increases risk of insulin-induced hypoglycemia; reduce prandial insulin dose when initiating pramlintide.

              • prednisolone

                prednisolone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

                prednisolone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

              • prednisone

                prednisone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

                prednisone decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • prochlorperazine

                prochlorperazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

                prochlorperazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • progesterone intravaginal gel

                progesterone intravaginal gel decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • promethazine

                promethazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

              • progesterone micronized

                progesterone micronized decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • propranolol

                propranolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • pseudoephedrine

                pseudoephedrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • quetiapine

                quetiapine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

                quetiapine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • quinapril

                quinapril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

                quinapril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • ramipril

                ramipril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                ramipril increases effects of liraglutide by unknown mechanism. Use Caution/Monitor. ACE inhibitors may increase hypoglycemic effect. Monitor glycemic control especially during the first month of treatment with an ACE inhibitor. .

              • repaglinide

                liraglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

              • risperidone

                risperidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • risperidone

                risperidone, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • ritonavir

                ritonavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

                ritonavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • rosiglitazone

                rosiglitazone, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

                liraglutide, rosiglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

              • sacubitril/valsartan

                sacubitril/valsartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

                sacubitril/valsartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                sacubitril/valsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • salsalate

                salsalate increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

              • saquinavir

                saquinavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • saquinavir

                saquinavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • saxagliptin

                liraglutide, saxagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

                saxagliptin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • semaglutide

                semaglutide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin dose may reduce hypoglycemia risk.

              • sitagliptin

                liraglutide, sitagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

              • sitagliptin

                sitagliptin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • sodium sulfate/?magnesium sulfate/potassium chloride

                sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              • sodium sulfate/potassium sulfate/magnesium sulfate

                sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              • somapacitan

                somapacitan decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

                somapacitan decreases effects of liraglutide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

              • somatropin

                somatropin decreases effects of liraglutide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Somatropin may potentially diminish hypoglycemic effects of antidiabetic agent. May consider modifying therapy.

                somatropin decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Growth hormone decreases insulin sensitivity by opposing the effects of insulin on carbohydrate metabolism.

              • sotalol

                sotalol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • telmisartan

                telmisartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              • sulfadiazine

                sulfadiazine, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                sulfadiazine increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and sulfonamide antibiotics may require insulin dosage adjustment and increased glucose monitoring.

              • sulfisoxazole

                sulfisoxazole, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                sulfisoxazole increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and sulfonamide antibiotics may require insulin dosage adjustment and increased glucose monitoring.

              • telmisartan

                telmisartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

                telmisartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • testosterone

                testosterone increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • testosterone buccal system

                testosterone buccal system increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • testosterone intranasal

                testosterone intranasal increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • testosterone topical

                testosterone topical increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • thioridazine

                thioridazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

                thioridazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

              • thyroid desiccated

                thyroid desiccated decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • tipranavir

                tipranavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • timolol

                timolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • tipranavir

                tipranavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • tolazamide

                liraglutide, tolazamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

                tolazamide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • tolbutamide

                liraglutide, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

                tolbutamide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • torsemide

                torsemide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • triamcinolone acetonide injectable suspension

                triamcinolone acetonide injectable suspension decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully. .

              • trandolapril

                trandolapril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • tranylcypromine

                tranylcypromine, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • triamcinolone acetonide injectable suspension

                triamcinolone acetonide injectable suspension decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

              • trifluoperazine

                trifluoperazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

                trifluoperazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

              • valsartan

                valsartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

                valsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

                valsartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • ziprasidone

                ziprasidone, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

                ziprasidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              Minor (5)

              • acetaminophen

                liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

              • acetaminophen IV

                liraglutide decreases levels of acetaminophen IV by unspecified interaction mechanism. Minor/Significance Unknown.

              • digoxin

                liraglutide decreases levels of digoxin by unspecified interaction mechanism. Minor/Significance Unknown.

              • lovastatin

                liraglutide decreases levels of lovastatin by unspecified interaction mechanism. Minor/Significance Unknown.

              • stevia

                stevia increases effects of insulin degludec by pharmacodynamic synergism. Minor/Significance Unknown.

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              Adverse Effects

              >1-10%

              Nasopharyngitis (9.6 %)

              Headache (9.1%)

              Nausea (7.8%)

              Diarrhea (7.5%)

              Increased lipase (6.7%)

              Upper respiratory tract infection (5.7%)

              Mildly elevated serum bilirubin concentrations (4%)

              Injection site reactions (2.6%)

              <1%

              Cholelithiasis (0.3%)

              Cholecystitis (0.2%)

              Frequency Not Defined

              Hypoglycemia

              Weight gain

              Peripheral edema

              Increased pulse 2-3 bpm

              Lipodystrophy at injection site

              Systemic allergy

              Immunogenicity

              Postmarketing Reports

              Liraglutide

              • Medullary thyroid carcinoma
              • Dehydration resulting from nausea, vomiting, and diarrhea
              • Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis
              • Angioedema and anaphylactic reactions
              • Allergic reactions: Rash and pruritus
              • Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death
              • Hepatobiliary disorders: Elevations of liver enzymes, hyperbilirubinemia, cholestasis, hepatitis
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              Warnings

              Black Box Warnings

              Thyroid tumor risk

              • Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both sexes of rats and mice
              • Unknown whether liraglutide/insulin degludec causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined
              • Contraindicated with a personal or family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2)
              • Inform patients of the potential risk for MTC with use and instruct them on symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness)
              • Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC

              Contraindications

              Patients with a personal or family history of MTC and in patients with MEN 2 (See Black Box Warnings)

              During episodes of hypoglycemia

              Hypersensitivity to either of the active drugs or any excipients; serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide

              Cautions

              Potential thyroid cancer risk (see Contraindications and Black Box Warnings)

              Severe, life-threatening, generalized allergy, including anaphylaxis, angioedema, bronchospasm, hypotension, and shock can occur; anaphylaxis and angioedema have been reported with GLP-1 receptor agonists

              Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, reported postmarketing with liraglutide

              Do not share insulin pens between patients

              Caution when changing dosage regimens; increase frequency of blood glucose monitoring to detect hypoglycemia or hyperglycemia

              Do not exceed maximum dose or use with other GLP-1 agonists or basal insulins

              Hypoglycemia is the most common adverse effect of insulin; self-monitoring of blood glucose is essential to prevent and manage hypoglycemia

              Acute kidney injury reported postmarketing with liraglutide, some of which required hemodialysis

              Increased risk for hypokalemia; insulin shifts potassium from the extracellular to intracellular space

              Increased risk of fluid retention and congestive heart failure with coadministration of peroxisome proliferator-activated receptor (PPAR)-gamma agonists (thiazolidinediones)

              No clinical studies have established conclusive evidence of macrovascular risk reduction with any antidiabetic drugs

              Cholelithiasis/cholecystitis reported with therapy; if cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated

              Drug interaction overview

              • Drugs that may increase hypoglycemia risk
                • May require dose reduction and increased glucose monitoring frequency if coadministered with drugs that cause hypoglycemia
                • Examples include antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (eg, octreotide), and sulfonamide antibiotics
              • Drugs that may decrease blood glucose-lowering effect of liraglutide/insulin degludec
                • May require dose increase and increased glucose monitoring frequency if coadministered with drugs that increase blood glucose
                • Examples include atypical antipsychotics (eg, olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (eg, in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (eg, albuterol, epinephrine, terbutaline), and thyroid hormones
              • Drugs that may increase or decrease the blood glucose-lowering effects of liraglutide/insulin degludec
                • Dose adjustment in increased blood glucose monitoring may be required
                • Examples include alcohol, beta-blockers, clonidine, and lithium salts; pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia
              • Drugs that may blunt signs and symptoms of hypoglycemia
                • Increase frequency of blood glucose monitoring
                • Examples include beta-blockers, clonidine, guanethidine, and reserpine
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              Pregnancy

              Pregnancy

              Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy

              Use during pregnancy only if the potential benefit justifies the potential risk to the fetus

              There are no available data with insulin degludec or liraglutide in pregnant women to inform a drug-associated risk for major birth defects or miscarriage

              There are clinical considerations regarding the risks of diabetes in pregnancy; poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications; poorly controlled diabetes mellitus increases fetal risk for major birth defects, stillbirth, macrosomia related morbidity

              Lactation

              There are no data on presence of liraglutide or insulin degludec in human milk, effects on breastfed infant, or on milk production; in lactating rats, insulin degludec and liraglutide, were present in milk

              Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Insulin degludec: Regulates glucose metabolism

              Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production

              Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis

              Liraglutide: Glucagon-like peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying

              Absorption

              Following based on maximum daily dose of 50 units/1.8 mg

              Peak plasma concentration: 5196 pmol/L (insulin degludec); 55 ng/mL (liraglutide)

              AUC (1-24 hr): 113 h·nmol/L (insulin degludec); 1227 h·nmol/mL (liraglutide)

              Steady state attained: 2-3 days

              Distribution

              Protein bound: >99% (insulin degludec); >98% (liraglutide)

              Metabolism

              Insulin degludec: Degradation is similar to that of human insulin; all metabolites formed are inactive

              Liraglutide: During the initial 24 hr following administration of a single dose to healthy subjects, the major component in plasma was intact liraglutide; endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination

              Elimination

              Half-life: ~25 hr (insulin degludec); ~13 hr (liraglutide)

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              Administration

              SC Administration

              Administer at the same time each day with or without food

              Inject SC in thigh, upper arm, or abdomen

              Rotate injection site within the same region from 1 injection to the next to reduce lipodystrophy risk

              Do not administer IV, IM, or by infusion pump

              Do not dilute or mix with any other insulin products or solutions

              Do not split the dose

              Caution in patients with visual impairment who may rely on audible clicks to dial their dose

              Missed doses

              • Instruct patients who miss a dose to resume the once-daily regimen as prescribed with the next scheduled dose
              • Do not administer an extra dose or increase the dose to make up for the missed dose
              • If >3 days have elapsed since the last dose, reinitiate at the starting dose (ie, 16 units) to mitigate any gastrointestinal symptoms associated with reinitiation of treatment

              Storage

              Prior to first use

              • Refrigerate between 2-8°C (36-46°F) until the expiration date printed on the label
              • Store prefilled pens in the carton so they will stay clean and protected from light
              • Do not store in the freezer or directly adjacent to the refrigerator cooling element
              • Do not freeze
              • Do not use if it has been frozen

              After first use

              • May be stored for 21 days at controlled room temperature (59-86°F; 15-30°C) or refrigerated (36-46°F; 2-8°C)
              • Keep all pens away from direct heat and light
              • Always remove the needle after each injection and store the pen without a needle attached; this prevents contamination and/or infection, or leakage of the pen, and ensures accurate dosing
              • Always use a new needle for each injection to prevent contamination
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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.