OSENI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OSENI (OSENI).
OSENI is a combination of alogliptin (DPP-4 inhibitor) and pioglitazone (PPARγ agonist). Alogliptin increases incretin levels, enhancing glucose-dependent insulin secretion and suppressing glucagon. Pioglitazone improves insulin sensitivity in adipose tissue, liver, and muscle.
| Metabolism | Alogliptin: minimal metabolism via CYP2D6 and CYP3A4; primarily excreted unchanged in urine. Pioglitazone: extensively metabolized via CYP2C8 and CYP3A4; minor metabolites active. |
| Excretion | Oseni (alogliptin and pioglitazone): Alogliptin: 60-71% renally excreted unchanged; pioglitazone: 15-30% renally, 60% biliary/fecal. |
| Half-life | Alogliptin: 12.4-21.4 hours; pioglitazone: 3-7 hours; clinical context: allows once-daily dosing. |
| Protein binding | Alogliptin: 20% bound to plasma proteins; pioglitazone: >99% bound to albumin. |
| Volume of Distribution | Alogliptin: 1.6-2.0 L/kg; pioglitazone: 0.25-0.35 L/kg; reflects distribution into tissues. |
| Bioavailability | Alogliptin: 100% after oral administration; pioglitazone: 83% after oral administration. |
| Onset of Action | Oral: 1-2 hours for alogliptin (DPP-4 inhibition), 30-60 minutes for pioglitazone (enhanced insulin sensitivity). |
| Duration of Action | 24 hours for both components, supporting once-daily dosing. |
1 tablet orally once daily. Each tablet contains alogliptin 12.5 mg and pioglitazone 15 mg, 25 mg, or 30 mg. Maximum daily dose: alogliptin 25 mg/pioglitazone 45 mg.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥60 mL/min/1.73 m²: no adjustment. eGFR 30-59: alogliptin maximum 12.5 mg/pioglitazone maximum 30 mg once daily. eGFR <30: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: use with caution; pioglitazone contraindicated if active liver disease or ALT >2.5x ULN. Child-Pugh Class C: contraindicated. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | Start with lower doses of pioglitazone (15 mg) due to increased risk of edema and fractures. Monitor renal function; adjust alogliptin per eGFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OSENI (OSENI).
| Breastfeeding | No data available on alogliptin or pioglitazone in human milk. M/P ratio unknown. Pioglitazone is excreted in rat milk. Risk to infant cannot be excluded. Use caution; consider alternative therapies if breastfeeding. |
| Teratogenic Risk | Pregnancy Category C for alogliptin; no adequate human studies. Category N for pioglitazone. In animal studies, alogliptin showed no teratogenicity at exposures up to 100 times human exposure. Pioglitazone caused delayed parturition and embryotoxicity at high doses. First trimester: insufficient data; second/third trimester: potential for fetal hyperinsulinemia and macrosomia due to maternal hyperglycemia. Avoid use during pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Pioglitazone may cause or exacerbate congestive heart failure. Monitor patients for signs/symptoms. Not recommended in NYHA Class III/IV heart failure. OSENI is not indicated for use in these patients.
| Serious Effects |
["History of heart failure (NYHA Class III/IV)","Active bladder cancer","History of pancreatitis","Severe renal impairment (<30 mL/min) or ESRD requiring dialysis","Hypersensitivity to components","Type 1 diabetes or diabetic ketoacidosis"]
| Precautions | ["Congestive heart failure","Bladder cancer risk (pioglitazone)","Hepatic effects (pioglitazone)","Pancreatitis (alogliptin)","Hypoglycemia with insulin/secretagogues","Arthralgia (DPP-4 inhibitors)","Bullous pemphigoid (DPP-4 inhibitors)","Macrovascular outcomes: no evidence of benefit","Use in renal impairment: alogliptin dose adjustment required based on eGFR"] |
Loading safety data…
| Fetal Monitoring | Monitor blood glucose and HbA1c regularly. Assess fetal growth via ultrasound due to risk of macrosomia. Monitor for signs of placental insufficiency. Check liver function tests periodically due to pioglitazone's potential for hepatotoxicity. Monitor for edema and heart failure symptoms. |
| Fertility Effects | Alogliptin: no known effect on fertility. Pioglitazone: may restore ovulation in anovulatory women with insulin resistance; increased risk of unintended pregnancy. Men: no significant impact on spermatogenesis. |