Dosing & Uses
Dosage Forms & Strengths
Diabetes Mellitus Type 2
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Starting dose based on patient’s current regimen
Take PO BID with food; gradually escalation dose to reduce GI side effects caused by metformin
Not to exceed 25 mg/2000 mg per day
- Obtain eGFR before starting metformin
- eGFR <30 mL/min/1.73 m²: Contraindicated
- eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment
- Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly)
- If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated
- If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug
Safety and efficacy not established
Serious - Use Alternative
Significant - Monitor Closely
Upper respiratory tract infection (8%)
Back pain (4.3%)
Urinary tract infection (4.2%)
Severe and disabling arthralgia
Black Box Warnings
Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
- Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation
- Characterized by blood lactate levels >5 mmol/L, decreased blood pH, electrolyte disturbances with an increased anion gap, and increased lactate/pyruvate ratio
- Risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute CHF
- Onset is often subtle, accompanied only by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress)
- Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate
- If acidosis is suspected, discontinue alogliptin/metformin and hospitalize the patient immediately
Renal impairment (ie, eGFR <30 ml/min/1.73 m²); renal impairment may also result from medical conditions (eg, shock, acute MI, septicemia)
Acute or chronic metabolic acidosis, including diabetic ketoacidosis; diabetic ketoacidosis should be treated with insulin
Hypersensitivity to alogliptin or metformin, including anaphylaxis, angioedema, or severe cutaneous adverse reactions including Stevens-Johnson syndrome
Lactic acidosis (see Black Box Warnings)
Caution with sensitivity to another DPP-4 inhibitor or metformin; discontinue if serious hypersensitivity reaction suspected (see Contraindications)
Fatal and nonfatal hepatic failure reported; type 2 DM is also known to cause fatty liver disease and liver enzyme elevation; monitor carefully and interrupt alogliptin treatment if LFTs elevated, do not restart alogliptin without another explanation for the liver test abnormalities
Insulin and insulin secretagogues (eg, sulfonylureas) are known to cause hypoglycemia; therefore, a lower dose of insulin of insulin secretagogue may be needed to minimize hypoglycemia risk
Coadministration with drugs that may affect renal function or metformin elimination
Temporarily withhold metformin for any surgical procedures that restrict fluid/food intake
Hypoxic conditions (eg, shock, acute CHF, acute MI) associated with lactic acidosis (see Black Box Warnings)
Alcohol potentiates metformin’s effect on lactate metabolism; avoid excessive alcohol intake
Metformin may decrease vitamin B12 levels
Hypoglycemia may occur with metformin if calorie intake is deficient
Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
Iodinated contrast imaging procedures
- Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
- Reevaluate eGFR 48 hr after the imaging procedure; restart metformin if renal function is stable
Congestive heart failure (CHF) risk
- The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial enrolled 5,380 patients with type 2 diabetes and recent acute coronary syndrome
- Hospitalization for CHF was observed in 106 (3.9%) patients treated with alogliptin and 89 (3.3%) patients treated with placebo; although the difference was not statistically significant (hazard ratio, 1.19), heart failure was not an end point of the study
- Health care professionals should consider discontinuing medications containing alogliptin in patients who develop heart failure and monitor their diabetes control
- Lancet. 2015 May 23;385(9982):2067-76
Pregnancy & Lactation
Pregnancy Category: B
Lactation: Unknown whether distributed in breast milk
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.
Mechanism of Action
Alogliptin: Selective dipeptidyl peptidase-4 (DPP-4) inhibitor; slows inactivation of incretin hormones (eg, GLP-1, GIP), thereby reducing fasting and postprandial glucose concentrations in a glucose-dependent manner
Metformin: Biguanide; decreases hepatic glucose production, decreases GI glucose absorption, and increases target cell insulin sensitivity
Bioavailability: ~100% (alogliptin); 50-60% (metformin [fasted])
Peak plasma time: 1-2 hr (alogliptin)
Protein bound: 20% (alogliptin); negligible (metformin)
Vd: 417 L (alogliptin)
- Does not undergo extensive metabolism and 60-71% of the dose is excreted unchanged in the urine
- Active metabolite: N-demethylated (<1% of parent compound)
- Inactive metabolite: N-acetylated alogliptin (<6% of parent compound)
- Minor substrate of CYP3A4 and CYP2D6
- Excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion
- Half-life: 21 hr
- Renal clearance: 9.6 L/hr
- Total body clearance: 14 L/hr
- Excretion: 76% urine; 13% feces
- Half-life: 6.2 hr (plasma), 17.6 hr (blood); suggests erythrocyte mass a compartment of distribution
- Excretion: 90% urine
Metformin must be taken with food
Swallow whole, do not chew, split, or crush
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|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.|
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