ALOGLIPTIN AND METFORMIN HYDROCHLORIDE
Clinical safety rating: safe
Alcohol and contrast dye can increase risk of lactic acidosis Can cause lactic acidosis a rare but serious metabolic complication.
Alogliptin inhibits dipeptidyl peptidase-4 (DPP-4), increasing incretin levels (GLP-1, GIP), enhancing glucose-dependent insulin secretion and reducing glucagon secretion. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity.
| Metabolism | Alogliptin is minimally metabolized; CYP2D6 and CYP3A4 are involved to a minor extent. Metformin is excreted unchanged in urine (90%) and not metabolized. |
| Excretion | Alogliptin: 60–71% excreted unchanged in urine; metformin: 90% excreted unchanged in urine via glomerular filtration and tubular secretion. |
| Half-life | Alogliptin: terminal half-life 12–21 hours; metformin: plasma half-life 6.2 hours (elimination). Clinical context: allows once-daily dosing; metformin half-life prolonged in renal impairment. |
| Protein binding | Alogliptin: ~20% bound to plasma proteins (primarily albumin and α1-acid glycoprotein); metformin: negligible (<5%) binding to plasma proteins. |
| Volume of Distribution | Alogliptin: Vd 17–23 L (approx 0.24 L/kg for 70 kg); metformin: 654 ± 358 L (approx 9.3 L/kg), extensive tissue distribution. |
| Bioavailability | Alogliptin: ~100% oral bioavailability; metformin: 50–60% oral bioavailability (fasted). |
| Onset of Action | Oral: Alogliptin – within 1 hour for DPP-4 inhibition; metformin – peak effect on glucose at 1–3 hours post-dose. |
| Duration of Action | Alogliptin: DPP-4 inhibition sustained for 24 hours; metformin: glucose-lowering effect lasts 8–12 hours (dose-dependent). |
| Molecular Weight | 415.51 |
Oral, initial dose based on prior antidiabetic therapy and renal function; typical starting dose for combination therapy is 12.5 mg alogliptin / 500 mg metformin twice daily with meals; maximum dose is 25 mg alogliptin / 2000 mg metformin per day in divided doses.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if eGFR <30 mL/min/1.73 m2; for eGFR 30-44 mL/min/1.73 m2, maximum alogliptin dose 12.5 mg once daily; metformin should not be initiated if eGFR 30-44 mL/min/1.73 m2; for eGFR 45-59 mL/min/1.73 m2, maximum alogliptin 25 mg once daily; metformin dose reduction to 1000 mg/day maximum; assess renal function before initiation and at least annually. |
| Liver impairment | Contraindicated in patients with hepatic impairment (Child-Pugh class A, B, or C) due to metformin component; alogliptin has no dose adjustment per manufacturer, but combination is not recommended. |
| Pediatric use | Not established; safety and efficacy in pediatric patients (<18 years) have not been studied. |
| Geriatric use | Start at low end of dosing range due to age-related renal decline; monitor renal function closely; avoid starting metformin if eGFR <45 mL/min/1.73 m2; do not use if eGFR <30 mL/min/1.73 m2. |
| 1st trimester | Alogliptin: No adequate human data; animal data suggest risk. Metformin: Some studies show no increased risk of major malformations; however, oral hypoglycemics are generally avoided in favor of insulin. |
| 2nd trimester | Alogliptin: Avoid due to insufficient safety data. Metformin: May be used if insulin is not feasible; monitor for fetal growth. |
| 3rd trimester | Alogliptin: Avoid; potential for neonatal hypoglycemia. Metformin: Avoid near term due to risk of neonatal hypoglycemia and lactic acidosis; switch to insulin if possible. |
Clinical note
Alcohol and contrast dye can increase risk of lactic acidosis Can cause lactic acidosis a rare but serious metabolic complication.
| FDA category | Human |
| Placental transfer | Alogliptin: Unknown; likely crosses placenta due to low molecular weight. Metformin: Crosses placenta; concentrations in fetal plasma similar to maternal. |
■ FDA Black Box Warning
Lactic acidosis: Metformin-associated lactic acidosis (MALA) can occur due to drug accumulation, especially in patients with renal impairment, acute conditions like sepsis, dehydration, liver disease, or alcohol abuse. Symptoms include hypothermia, hypotension, and resistant bradyarrhythmias.
| Common Effects | Diarrhea |
| Serious Effects |
Renal impairment (eGFR <30 mL/min/1.73 m2)Acute or chronic metabolic acidosis including diabetic ketoacidosisHistory of hypersensitivity to alogliptin or metforminUse of iodinated contrast media (temporarily discontinue metformin)
| Precautions | Lactic acidosis (see black box warning), Pancreatitis: discontinue if suspected, Hypoglycemia when used with insulin or sulfonylurea, Renal impairment: contraindicated if eGFR < 30 mL/min/1.73 m²; not recommended if eGFR 30-45 mL/min/1.73 m², Heart failure: alogliptin may increase risk; consider risks/benefits, Severe and disabling arthralgia, Vitamin B12 deficiency with long-term metformin use, Acute kidney injury, sepsis, dehydration: temporarily discontinue metformin |
Loading safety data…
| Breastfeeding | Alogliptin: No data on excretion in human milk; potential for infant hypoglycemia. Metformin: Excreted into milk in low amounts; generally considered compatible with breastfeeding, but monitor infant for hypoglycemia. Combination: Caution advised; use only if clearly needed. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Alogliptin: Limited human data, animal studies show no increased risk at clinically relevant doses. Metformin: Not associated with increased risk of major malformations; some data suggest reduced risk of miscarriage in women with PCOS. First trimester: No clear evidence of teratogenicity for either component. Second and third trimesters: Metformin may be associated with reduced birth weight in infants of women with GDM; no specific fetal risks for alogliptin. Combined: Insufficient data to fully assess risk; weigh benefits vs. risks. |
| Fetal Monitoring | Monitor blood glucose levels, HbA1c, renal function (serum creatinine, eGFR), liver function, and signs of lactic acidosis (especially with renal impairment). Fetal monitoring: standard prenatal care, consider fetal growth ultrasonography. No specific additional monitoring required for alogliptin/metformin combination beyond routine diabetes management. |
| Fertility Effects | Alogliptin: No known adverse effects on fertility in animal studies. Metformin: May improve ovulation and fertility in women with PCOS due to insulin sensitization. No known negative impact on male or female fertility in humans. Theoretical risk of ovulation induction with combination therapy not established. |
| Food/Dietary | Alcohol may increase lactic acidosis risk; limit or avoid. No specific food interactions; take with meals to improve tolerability. Avoid high-fat meals if they worsen GI intolerance. |
| Clinical Pearls | Monitor renal function before initiation and periodically; contraindicated if eGFR <30 mL/min/1.73 m². Adjust metformin dose if eGFR 30-45. Assess for lactic acidosis symptoms (myalgia, abdominal pain, dyspnea). Alogliptin may cause acute pancreatitis; discontinue if suspected. Use caution with heart failure—ogliptin not associated with increased risk. |
| Patient Advice | Take with meals to reduce gastrointestinal side effects. · Do not exceed prescribed doses; skip if vomiting or unable to eat. · Report persistent stomach pain, nausea, or unusual fatigue (lactic acidosis). · Stop and seek medical help for severe abdominal pain (pancreatitis). · Avoid alcohol; increases risk of lactic acidosis and hypoglycemia. |