Alogliptin: A dipeptidyl peptidase-4 (DPP-4) inhibitor, alogliptin enhances glucose-dependent insulin secretion by prolonging the activity of incretin hormones (GLP-1 and GIP). These hormones suppress glucagon release, slow gastric emptying, and reduce hepatic glucose production (Lippincott). DPP-4 inhibition increases active incretin levels by 2-3 fold, improving both fasting and postprandial hyperglycemia (BNF).

Glimepiride: A sulfonylurea, glimepiride stimulates insulin secretion from pancreatic β-cells by binding to ATP-sensitive potassium (K⁺ATP) channels, causing cell depolarization and calcium influx. It also enhances peripheral insulin sensitivity (Lange).

Combined Effect: The dual action addresses insulin deficiency (glimepiride) and improves incretin-mediated glucose regulation (alogliptin), offering complementary glycemic control (BNF).

• Primary Indication: Management of type 2 diabetes mellitus in adults inadequately controlled by monotherapy (e.g., metformin) or as an adjunct to diet/exercise when dual therapy is warranted.
• Adjunctive Therapy: May be combined with other agents (e.g., metformin, insulin) under specialist guidance (BNF).

• Available Strengths: Alogliptin (12.5 mg or 25 mg) combined with glimepiride (1 mg, 2 mg, or 4 mg). Common formulations include 12.5/1, 12.5/2, 25/1, and 25/2 mg (BNF).
• Standard Dose: Once daily with the first meal of the day.
  • Alogliptin: Adjust for renal impairment (e.g., 12.5 mg daily if eGFR <60 mL/min; avoid if eGFR <30 mL/min).
  • Glimepiride: Initiate at 1–2 mg/day, titrated gradually to avoid hypoglycemia (max 8 mg/day).
• Elderly/Hepatic Impairment: Use lower glimepiride doses due to prolonged hypoglycemia risk (Lange).

• Alogliptin: Nasopharyngitis, headache, upper respiratory infections.
• Glimepiride: Hypoglycemia (dose-dependent), weight gain, dizziness.

Serious:

• Glimepiride: Severe hypoglycemia (especially in elderly/renal impairment), hemolytic anemia (rare), hypersensitivity.
• Alogliptin: Acute pancreatitis (rare), angioedema, joint pain (BNF).

• Contraindications:
  • Type 1 diabetes, diabetic ketoacidosis, severe renal/hepatic impairment.
  • Hypersensitivity to sulfonylureas or DPP-4 inhibitors.

• • Blood glucose (to detect hypoglycemia), renal function, HbA1c, and liver enzymes.
  • Signs of pancreatitis (e.g., severe abdominal pain, vomiting).

Category C (glimepiride); avoid due to hypoglycemia risk in neonates.

• Glimepiride:
  • CYP2C9 Inhibitors (e.g., fluconazole, amiodarone): Increase hypoglycemia risk.
  • Beta-blockers: Mask hypoglycemia symptoms.
  • Alcohol: Disulfiram-like reaction (rare) or potentiated hypoglycemia.
• Alogliptin:
  • CYP3A4 Inducers (e.g., rifampicin): May reduce efficacy.
• General:
  • Hypoglycemia risk heightened with insulin, other sulfonylureas, or GLP-1 agonists. Avoid concurrent use with pioglitazone due to additive edema risk (Lippincott).

• Generic: Alogliptin/glimepiride.

Brand Examples: Not widely marketed; available as generics in some regions (e.g., India).