What is Rezuoglar (glucagon-like peptide-1 receptor agonist)?

Rezuoglar: A Glucagon-Like Peptide-1 Receptor Agonist

Rezuoglar is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of type 2 diabetes mellitus and weight management, working by enhancing glucose-dependent insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through central nervous system effects. 1

Mechanism of Action

GLP-1 receptor agonists like Rezuoglar:

• Bind to and activate GLP-1 receptors on pancreatic β-cells, stimulating glucose-dependent insulin secretion (only when blood glucose is elevated) 1
• Inhibit glucagon secretion from pancreatic α-cells, reducing hepatic glucose output 1
• Delay gastric emptying by inhibiting gastric peristalsis and increasing pyloric tone, which slows absorption of nutrients 1
• Act on GLP-1 receptors in the hypothalamus and brainstem to reduce appetite and food intake, contributing to weight loss 1

Clinical Benefits

GLP-1 receptor agonists offer several important clinical advantages:

• Effective reduction of HbA1c levels by approximately 0.5-1.0 percentage points 1
• Significant weight loss effects (2-3 kg over 6 months for earlier agents; newer agents like semaglutide can produce 14.9% weight reduction from baseline) 1
• Low risk of hypoglycemia when used as monotherapy due to their glucose-dependent mechanism 1
• Cardiovascular benefits including reduced rates of non-fatal myocardial infarction, stroke, and cardiovascular death in high-risk patients 1
• Potential protective effects on β-cell function, possibly promoting cell proliferation and preventing apoptosis 1

Pharmacokinetics

GLP-1 receptor agonists have been molecularly modified to extend their duration of action:

• Short-acting agents (like exenatide) require once or twice-daily administration 1
• Long-acting agents have various mechanisms to prolong their half-lives:
  • Albumin binding (semaglutide, albiglutide) 1
  • Conjugation with immunoglobulin G fragments (dulaglutide) 1
  • Microsphere encapsulation for sustained release (long-acting exenatide) 1

Common Adverse Effects

The most common side effects of GLP-1 receptor agonists include:

• Gastrointestinal symptoms: nausea, vomiting, diarrhea (occurring in 30-45% of patients, typically transient and diminishing over time) 1
• Dyspepsia and gastroesophageal reflux 1
• Constipation 1
• Potential risk for gallbladder disorders 1
• Rare reports of pancreatitis (causal relationship not clearly established) 1

Clinical Use

GLP-1 receptor agonists are recommended for:

• Second-line therapy in combination with metformin for type 2 diabetes management 1, 2
• Treatment of obesity in patients with BMI >30 or >27 with weight-related comorbidities 1
• Cardiovascular risk reduction in patients with established cardiovascular disease or high cardiovascular risk 1

Important Clinical Considerations

• Start at a low dose and titrate gradually to minimize gastrointestinal side effects 1
• Use with caution in patients with gastroparesis due to effects on gastric emptying 1
• Monitor for potential delayed gastric emptying in perioperative settings, which may increase aspiration risk 1
• Consider the effects on gastric emptying when timing meals and other medications 1
• Tachyphylaxis to the gastric emptying effect may occur with continuous exposure, though glucose-lowering effects remain 1

GLP-1 receptor agonists represent an important class of medications that not only improve glycemic control but also offer significant benefits for weight management and cardiovascular risk reduction, making them valuable tools in the management of type 2 diabetes and obesity 1.