What are the FDA-approved meglitinides (Meglitinide analogs)?

From the Guidelines

The FDA has approved three meglitinides for use in the United States: repaglinide (Prandin), nateglinide (Starlix), and a combination medication containing repaglinide and metformin (Prandimet). These medications are used to treat type 2 diabetes by stimulating insulin release from the pancreas. Meglitinides work quickly and for a short duration, making them particularly useful for controlling post-meal blood sugar spikes.

Key Points to Consider

• Typical dosing for repaglinide ranges from 0.5 to 4 mg taken before meals (up to four times daily), while nateglinide is usually prescribed at 60-120 mg before meals 1.
• These medications should be taken 15-30 minutes before eating, and if a meal is skipped, the dose should also be skipped to avoid hypoglycemia.
• Meglitinides are beneficial for patients who need flexible meal timing or have kidney impairment where sulfonylureas might be contraindicated.
• Common side effects include hypoglycemia and weight gain, though generally less severe than with sulfonylureas.
• These medications work by binding to ATP-dependent potassium channels on pancreatic beta cells, causing membrane depolarization and insulin release.

Recommendations

• Rapid-acting secretagogues (meglitinides) can be used in place of sulfonylureas in patients with erratic meal schedules or those who have late postprandial hypoglycemia while receiving sulfonylurea therapy 1.
• Consider switching to SGLT2 inhibitors or GLP-1 receptor agonists in individuals with established CVD, chronic kidney disease, and heart failure, as they have demonstrated CVD benefit independent of A1C lowering 1.

From the FDA Drug Label

NATEGLINIDE tablets, for oral use Initial U. S. Approval: 2000 PRANDIN® (repaglinide) is an oral blood glucose-lowering drug of the meglitinide class used in the management of type 2 diabetes mellitus

The FDA has approved two meglitinides:

• Nateglinide (approved in 2000)
• Repaglinide 2 3

From the Research

FDA Approved Meglitinides

• The FDA has approved two meglitinide molecules, Repaglinide and Nateglinide, for the treatment of type 2 diabetes mellitus (T2DM) 4.
• Repaglinide is preferred due to its superior glycemic efficacy, with a mean decrement of glycosylated haemoglobin (HbA1c) ranging between -0.2 to -1.50% with individual therapy 4.
• Nateglinide is also effective in controlling postprandial hyperglycemia with minimal risk of hypoglycemia, making it useful in patients with variable meal timings, especially in the elderly, and in patients with renal failure 4.

Mechanism of Action

• Meglitinides stimulate insulin release by inhibiting ATP-sensitive potassium channels of the beta-cell membrane via binding to a receptor distinct from that of sulphonylureas (SUR1/KIR 6.2) 5.
• Repaglinide and Nateglinide have a distinct binding site at the β-cell membrane, which differs from that of sulfonylureas, and corresponds to greater insulinotropic effects with repaglinide than with glibenclamide and/or glimepiride 6.

Efficacy and Safety

• Meglitinides have modest efficacy with a mean decrement of glycosylated haemoglobin (HbA1c) ranging between -0.2 to -1.50% with individual therapy, and additional HbA1c reduction can occur with combination therapy with other oral hypoglycemics 4.
• Repaglinide and Nateglinide are generally well tolerated, with a tolerability profile similar to that of sulfonylurea drugs 6.
• The most common adverse effects of meglitinides are hypoglycemia related 7.

Other Meglitinides

• Mitiglinide, a rapid-acting insulin secretion-stimulating agent, is approved in Japan for the treatment of type 2 diabetes (T2DM), and has been shown to decrease A1C levels by 0.17 - 1.1% in clinical studies 7.
• Mitiglinide has selective action on the pancreatic β-cells, has greater affinity for β-cells, and limited metabolism when compared to other meglitinides, making it a potential option for patients with chronic kidney disease or at high risk of hypoglycemia 7.