ertugliflozin/metformin (Rx)

Brand and Other Names:Segluromet
  • Print

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

ertugliflozin/metformin

tablet

  • 2.5mg/500mg
  • 2.5mg/1000mg
  • 7.5mg/500mg
  • 7.5mg/1000mg

Type 2 Diabetes Mellitus

Indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing ertugliflozin or metformin, or in patients who are already treated with both ertugliflozin and metformin

Individualize starting dose based on patient’s current regimen, while not exceeding daily dose of ertugliflozin 15 mg and metformin 2000 mg

Take BID with meals

Patients on metformin: Switch to tablets containing 2.5 mg ertugliflozin, with a similar total daily dose of metformin

Patients on ertugliflozin: Switch to tablets containing 500 mg metformin, with a similar total daily dose of ertugliflozin

Patients already on ertugliflozin and metformin: Switch to tablets containing same total daily dose of ertugliflozin and a similar daily dose of metformin

To reduce GI adverse effects, gradually escalate dose for those initiating metformin

Adjust dose based on effectiveness and tolerability

Dosage Modifications

Concomitant use with insulin and insulin secretagogues may increase the risk of hypoglycemia; lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with ertugliflozin

Iodinated contrast imaging procedures

  • Discontinue at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR <60 mL/min/1.73 m², history of liver disease, alcoholism, heart failure, or in patients who will be administered intra-arterial iodinated contrast
  • Reevaluate eGFR 48 hr after the imaging procedure; restart drug if renal function is stable

Renal impairment

  • eGFR &g;e60 mL/min/1.73 m²: No dosage adjustment necessary
  • eGFR <30 mL/min/1.73 m²: Contraindicated
  • End-stage renal disease or dialysis: Contraindicated
  • eGFR 30-60 mL/min/1.73 m²
    • Initiation of ertugliflozin not recommended
    • Continued use not recommended with persistent eGFR 30-60 mL/min/1.73 m²

Hepatic impairment

  • Not recommended with hepatic impairment
  • Metformin has been associated with some cases of lactic acidosis in patients with hepatic impairment

Dosing Considerations

In patients with volume depletion not previously treated with ertugliflozin, correct this condition before initiating

Assess renal function before initiating and periodically thereafter

Limitations of use

  • Not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis

<18 years: Safety and efficacy not established

≥65 years: No dosage adjustment necessary based on age

Elderly patients are more likely to have decreased renal function; because renal function abnormalities can occur after initiating ertugliflozin, and metformin is known to be substantially excreted by the kidneys, care should be taken in dose selection in elderly patients (see Adult Dosing, Dosage Modifications)

Assess renal function in elderly patients prior to initiating dosing and periodically thereafter

Patients aged ≥65 years had a higher incidence of adverse reactions related to volume depletion compared with younger patients

Next:

Interactions

Interaction Checker

and ertugliflozin/metformin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10% (Ertugliflozin)

            Female genital mycotic infections (9.1-12.2%)

            1-10% (Ertugliflozin)

            Volume depletion adverse effects (1.9-4.4%)

            Male genital mycotic infections (3.7-4.2%)

            Urinary tract infections (4-4.1%)

            Headache (2.9-3.5%)

            Vaginal pruritus (2.4-2.8%)

            Increased urination (2.4-2.7%)

            Nasopharyngitis (2-2.5%)

            Back pain (1.7-2.5%)

            Renal adverse effects (1.3-2.5%)

            Weight decreased (1.2-2.4%)

            Thirst (1.4-2.7%)

            >5% (Metformin)

            Initiating drug

            • Diarrhea
            • Nausea
            • Vomiting
            • Flatulence
            • Abdominal discomfort
            • Indigestion
            • Asthenia
            • Headache

            Long-term use

            • Decreased vitamin B-12 absorption, which may very rarely result in significant deficiency (eg, megaloblastic anemia)
            Previous
            Next:

            Warnings

            Black Box Warnings

            Metformin

            • Lactic acidosis
              • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias
              • Onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, abdominal pain)
              • Metformin-associated lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL
              • Risk factors include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors [eg, topiramate]), age ≥65 years, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute CHF), excessive alcohol intake, and hepatic impairment
              • If metformin-associated lactic acidosis is suspected, immediately discontinue drug and institute general supportive measures in a hospital setting
              • Prompt hemodialysis is recommended

            Contraindications

            Hypersensitivity

            Severe renal impairment, end-stage renal disease, or dialysis

            Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma

            Cautions

            Cases of metformin-associated lactic acidosis reported, including fatalities (see Black Box Warnings and Contraindications)

            Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary

            Causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment, with low systolic blood pressure, on diuretics, or who are elderly

            Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, reported; before initiating, consider factors that may predispose patient to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse; monitor for ketoacidosis and temporarily discontinue in clinical situations known to predispose to ketoacidosis (eg, prolonged fasting owing to acute illness or surgery)

            Renal impairment may occur owing to intravascular volume contraction; before initiating, consider factors that may predispose patients to acute kidney injury, including hypovolemia, chronic renal insufficiency, CHF, and concomitant medications (eg, diuretics, ACE inhibitors, ARBs, NSAIDs); consider temporarily discontinuing ertugliflozin in any setting of reduced oral intake or fluid loss; monitor for signs and symptoms of acute kidney injury, and, if evident, discontinue drug promptly and institute treatment (see Contraindications and Dosage Modifications)

            Serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization reported in patients receiving SGLT2 inhibitors

            An increased risk for lower limb amputation (primarily of the toe) has been observed in clinical studies with another SGLT2 inhibitor; before initiating, consider factors that may predispose patient to increased risk of amputations (eg, history of prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers)

            Genital mycotic infections may occur; patients with history of genital mycotic infections and uncircumcised males are more susceptible

            Dose-related increases in LDL-C reported

            Vitamin B12 levels may decrease; metformin may interfere with absorption from B12-intrinsic factor complex

            No conclusive evidence of macrovascular risk reduction with empagliflozin or any other antidiabetic agent

            Drug interaction overview

            • Closely monitor if coadministered with drugs that affect glycemic control by causing hyperglycemia (eg, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid drugs, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, CCBs, isoniazid)
            • Ertugliflozin
              • Hypoglycemia risk increased with insulin and insulin secretagogues (eg, sulfonylureas); a lower dose of insulin or insulin secretagogue may be required
              • Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors, as SGLT2 inhibitors increase urinary glucose excretion and lead to positive urine glucose tests; use alternative methods to monitor glycemic control
              • Monitoring glycemic control with 1,5-AG assay is not recommended, as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors; use alternative methods to monitor glycemic control
            • Metformin
              • Coadministration with carbonic anhydrase inhibitors (topiramate, zonisamide, acetazolamide, dichlorphenamide) may increase risk for lactic acidosis; these drug cause a decrease in serum bicarbonate and induce non-anion gap hyperchloremic metabolic acidosis
              • Drugs that interfere with renal tubular transport (OCT2 inhibitors, MATE inhibitors) may increase systemic exposure to metformin and increase risk for lactic acidosis
              • Alcohol is known to increase effect of metformin on lactate metabolism
            Previous
            Next:

            Pregnancy

            Pregnancy

            Ertugliflozin

            • Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy
            • Data are limited in pregnant women and are not sufficient to determine a drug-associated risk of adverse developmental outcomes; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
            • Animal data
              • In animal studies, adverse renal changes were observed in rats when ertugliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy; doses ~13 times the maximum clinical dose caused renal pelvic and tubule dilatations and renal mineralization that were not fully reversible
              • There was no evidence of fetal harm in rats or rabbits at exposures of ertugliflozin ~300 times higher than the maximal clinical dose of 15 mg/day when administered during organogenesis

            Metformin

            • Published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy
            • However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups
            • Animal data
              • Metformin did not adversely affect development outcomes when administered to rats and rabbits at doses up to 600 mg/kg/day
              • This represents an exposure of about 2 and 6 times the maximum recommended human dose of 2,000 mg based on body surface area comparisons for rats and rabbits, respectively
              • Determination of fetal concentrations demonstrated a partial placental barrier to metformin

            Lactation

            Not recommended while breastfeeding

            Ertugliflozin

            • Unknown if distributed in human breast milk
            • Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney
            • Because of the potential for serious adverse reactions in a breastfed infant, advise women that ertugliflozin is not recommended while breastfeeding

            Metformin

            • Published clinical lactation studies report that metformin is present in human milk, which resulted in infant doses approximately 0.11-1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.13 and 1
            • However, the studies were not designed to definitely establish the risk of use of metformin during lactation because of small sample size and limited adverse event data collected in infants

            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.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Ertugliflozin: Selective sodium-glucose transporter-2 (SGLT2) inhibitor; lowers the renal glucose threshold (ie, the plasma glucose concentration which exceed the maximum glucose reabsorption capacity of the kidney); lowering the renal glucose threshold results in increased urinary glucose excretion

            Metformin: Decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization; improves glucose tolerance by lowering both basal and postprandial plasma glucose

            Absorption

            Ertugliflozin

            • Peak plasma time: 1 hr (fasting); 2 hr (high-fat, high-caloric meal)
            • Peak plasma concentration, steady-state: 81.3 ng/mL (5 mg qDay); 268 ng/mL (15 mg qDay)
            • AUC, steady-state: 398 ng∙hr/mL (5 mg qDay); 1,193 ng∙hr/mL (15 mg qDay)
            • Steady-state reached after 4-6 days
            • Bioavailability, 15-mg dose: ~100%

            Metformin

            • Steady-state reached after 24-48 hr
            • Bioavailability, 500-mg dose: 50-60%
            • Food decreases extent of and slightly delays absorption

            Distribution

            Ertugliflozin

            • Vd, steady-state: 85.5 L
            • Protein binding: 93.6%
            • Blood-to-plasma concentration ratio of ertugliflozin: 0.66

            Metformin

            • Vd: 654 L
            • Protein binding: Negligible

            Metabolism

            Ertugliflozin

            • Major metabolic pathway for ertugliflozin is UGT1A9 and UGT2B7-mediated O-glucuronidation to 2 glucuronides (pharmacologically inactive at clinically relevant concentrations)
            • CYP-mediated (oxidative) metabolism of ertugliflozin is minimal (12%)

            Metformin

            • Does not undergo hepatic nor biliary metabolism

            Excretion

            Ertugliflozin

            • Half-life: 16.6 hr
            • Clearance: 11.2 L/hr
            • Excretion, oral [14C]-ertugliflozin solution: Feces (40.9%); urine (50.2%)
            • Excretion, unchanged ertugliflozin: Feces (33.8%); urine (1.5%)

            Metformin

            • Half-life: 17.6 hr (blood); 6.2 hr (plasma)
            • Excretion: ~90% urine (unchanged)
            Previous
            Next:

            Administration

            Oral Administration

            Take in the morning qDay, with or without food

            Missed dose

            • Take it as soon as you remember
            • If it is almost time for scheduled next dose, skip missed dose and take the next regularly scheduled time
            • Do not take 2 doses at the same time

            Storage

            Store at room temperature between 68-77°F (20-25°C); excursions permitted between 59-86°F (15-30°C)

            Keep tablets dry

            Store blister packs in the original package

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            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.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.