Repaglinide + Voglibose

Overview

Repaglinide + Voglibose is prescribed for Type 2 Diabetes Mellitus as an adjunct to diet and exercise to improve glycemic control in adults. It is particularly beneficial in managing postprandial (after-meal) blood glucose excursions.
Pharmacological Classification: Antidiabetic combination medication comprising a meglitinide (repaglinide) and an alpha-glucosidase inhibitor (voglibose).
Mechanism of Action: Repaglinide stimulates insulin release from the pancreas, while voglibose delays the intestinal absorption of glucose. This combined action helps regulate blood sugar levels, especially after meals.

No widely recognized alternate names exist for the combination product itself. Individual components have alternate names (e.g., Prandin for repaglinide).
Brand Names: Several brand names exist including Vogli Rapid, Eurepa V, Volibo R, Volix R, Voglimac R HD, Voglitor R, Vobit R, PPG R, Voglios RP, and Volga R. Brand names may vary regionally.

Pharmacodynamics: Repaglinide binds to ATP-sensitive potassium channels on pancreatic beta-cells, leading to depolarization and calcium influx, which triggers insulin release. Voglibose inhibits alpha-glucosidase enzymes in the small intestine, slowing the breakdown of complex carbohydrates into glucose and delaying glucose absorption.
Pharmacokinetics: Repaglinide is rapidly absorbed and extensively metabolized by the liver (primarily CYP3A4 and CYP2C8), with renal excretion of metabolites. Voglibose is minimally absorbed and primarily acts locally in the intestine. A small amount is metabolized by intestinal bacteria, and a negligible fraction is excreted renally.
Mode of Action:
- Repaglinide: Targets pancreatic beta-cells, enhancing insulin secretion.
- Voglibose: Acts locally in the intestinal lumen, inhibiting alpha-glucosidase.
Receptor Binding/Enzyme Inhibition: Repaglinide binds to specific sites on ATP-sensitive potassium channels. Voglibose competitively inhibits alpha-glucosidase enzymes.
Elimination Pathways:
- Repaglinide: Hepatic metabolism (CYP3A4 and CYP2C8) followed by renal excretion of metabolites.
- Voglibose: Minimal systemic absorption; primarily excreted unchanged in feces, with a small fraction metabolized by intestinal bacteria.

Initial: Repaglinide 0.5mg + Voglibose 0.3mg thrice daily immediately before main meals.
Titration: Repaglinide can be titrated up to 4mg per meal based on blood glucose response.
Maximum: Repaglinide 16mg/day total (divided doses).

Elderly Patients: Start with a lower dose of repaglinide (0.5 mg before meals) and titrate cautiously. Monitor closely for hypoglycemia. For voglibose, no specific dose adjustments are generally recommended for the elderly, but caution should be exercised in those with liver or kidney impairment.
Patients with Renal Impairment: Repaglinide can be used without dosage adjustments in mild to moderate renal impairment. Voglibose requires caution and potential dose reduction in moderate to severe renal impairment.
Patients with Hepatic Dysfunction: Both repaglinide and voglibose require caution and lower starting doses in patients with hepatic impairment. Allow longer intervals between dosage adjustments.
Patients with Comorbid Conditions: Carefully consider other medical conditions (e.g., cardiovascular disease) and potential drug interactions when adjusting dosage.

Not typically used in these settings. The combination is primarily for oral management of Type 2 Diabetes Mellitus.

Adjust based on blood glucose (fasting and postprandial), HbA1c, and patient response.
Consider renal/hepatic function, comorbidities, and concomitant medications.

Potential for worsening glycemic control over time (secondary failure) requiring adjustments to therapy.

CYP3A4/2C8 inducers/inhibitors: May alter repaglinide metabolism (e.g., ketoconazole, rifampin).
Beta-blockers: Can mask symptoms of hypoglycemia.
Other antidiabetic drugs: Increased risk of hypoglycemia (e.g., insulin, metformin, sulfonylureas).
Gemfibrozil: Contraindicated with repaglinide.
Clopidogrel, Cyclosporine: Dosage adjustments may be needed.
Alcohol: Increased risk of hypoglycemia and lactic acidosis (with voglibose).

Pregnancy: Repaglinide is not recommended during pregnancy. Voglibose is classified as Pregnancy Category B, meaning animal studies show no risk, but human data are limited. Use only if clearly needed and after careful risk-benefit assessment.
Breastfeeding: Repaglinide is present in rat milk; use with caution in humans. Voglibose is present in human milk at very low levels, but use with caution. If possible, consider alternative therapies while breastfeeding.

Please refer to the information provided above for a concise summary.