GLP-1 Receptor Agonists

Introduction

Glucagon-like peptide-1 (GLP-1) receptor agonists (incretin mimetics) lower blood glucose by increasing insulin secretion, suppressing glucagon secretion and slowing gastric emptying.

• Also, they reduce food intake (by an effect on satiety) and are associated with modest weight gain.

They are used in patients with type 2 diabetes in combination with other drugs (such as metformin, sulfonylurea and insulin).

• GLP-1 receptor agonists should not be combined with DDP-4 inhibitors as they both belong to the same class of incretins.

Method of Administration

GLP-1 agonists are mostly administered by subcutaneous injection, either

• Once daily
• Exenatide, liraglutide, lixisenatide
• Once weekly
• Extended release exenatide, albiglutide, dulaglutide.

Semaglutide is currently the only GLP-1 receptor agonist available in both an injectable and an oral formulation.

Adverse Reactions

All GLP-1 receptor agonists have been associated with nausea and other gastrointestinal disturbances.

• However, once therapy have been established, the incidence of these side effects decreases.

Pancreatitis is rare but potentially severe.

Liraglutide, semaglutide, dulaglutide and once-weekly exenatide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (adverse effect found in rodent studies but not in human).

Drug Interactions

Since GLP-1 receptor agonists can cause a delay in gastric emptying, they may influence the absorption of other medicines administered at the same time.

• It is advised that any narrow-therapeutic-index drugs taken concomitantly are monitored carefully.

External Links

• Glucagon-like Peptide-1 Receptor Agonists, 2023
  
• Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial, 2023