Makindo Medical Notes

GLP-1 (Glucagon-like Peptide-1) receptor agonists are used for type 2 diabetes mellitus (T2DM) and, increasingly, for obesity management. They mimic the incretin hormone GLP-1, enhancing insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting satiety 🍽️.

⚙️ Mechanism of Action

They act like natural GLP-1 from the gut, working in four key ways:

• Insulin Boost 🟢: Stimulate pancreatic β-cells to release insulin — only when glucose is high → low hypoglycaemia risk.
• Glucagon Block 🔴: Suppress α-cell glucagon ➝ ↓ hepatic glucose output.
• Slow Stomach Emptying 🕒: Slows carb absorption → blunts post-meal glucose spikes.
• Appetite Control 🍽️: Acts on hypothalamus to increase satiety → weight loss benefit.

📌 Indications

• T2DM: Monotherapy or combined with metformin/SGLT2i/insulin when HbA1c remains above target.
• Obesity: NICE now approves semaglutide (Wegovy) for weight management in certain BMI thresholds 🎯.
• Cardiovascular Risk: Agents like liraglutide and semaglutide reduce major adverse CV events ❤️.

💊 Common Agents

• 🟠 Exenatide (Byetta BD, Bydureon weekly)
• 🔵 Liraglutide (Victoza daily for T2DM; Saxenda for obesity)
• 🟢 Semaglutide (Ozempic weekly injection, Rybelsus oral, Wegovy for obesity)
• 🟣 Dulaglutide (Trulicity weekly)
• ⚪ Albiglutide (Tanzeum – less used)
• 🟤 Lixisenatide (Adlyxin daily)

🌟 Benefits

• 📉 HbA1c reduction: Typically 1.0–1.5% when added to metformin.
• ⚖️ Weight loss: Average 5–10% with semaglutide ➝ major impact in obesity medicine.
• 🔒 Low hypoglycaemia risk: Compared with sulfonylureas/insulin.
• ❤️ Cardiovascular protection: Proven in CVOTs (LEADER, SUSTAIN-6, REWIND).
• 🩺 Possible renal benefit: ↓ albuminuria, slower CKD progression.

⚠️ Adverse Effects

• 🤢 GI upset: Nausea, vomiting, diarrhoea (commonest) — usually settle after 2–4 weeks. Start low, go slow.
• 💉 Injection reactions: Local redness/itching.
• 🔥 Pancreatitis risk: Rare but serious — avoid in those with previous pancreatitis.
• 🦋 Thyroid concerns: Contraindicated with MEN2 or family history of medullary thyroid carcinoma.
• ⚡ Hypersensitivity: Rare angioedema/anaphylaxis reported.

🧑‍⚕️ Clinical Considerations

• Combination therapy: Often paired with metformin or SGLT2 inhibitors. Insulin dose may need reduction to avoid hypos.
• Administration: Mostly SC injection (daily/weekly); semaglutide also has an oral form 💊.
• UK practice 🏥: NICE recommends GLP-1 RAs if BMI ≥35 (or ≥30 in some cases) and T2DM not controlled with triple therapy.
• Sick-day rules: Stop if vomiting severely → risk of dehydration and AKI.

🔎 Clinical Pearls

• Patients often lose interest in food — encourage protein intake to avoid sarcopenia.
• GI side-effects improve if meals are smaller and less fatty 🍔❌.
• Weight loss benefit is independent of diabetes — increasingly used in non-diabetic obesity.
• CV outcome data are strongest for liraglutide, semaglutide, and dulaglutide.

✅ Conclusion

GLP-1 receptor agonists are a cornerstone in modern diabetes care and obesity management. They combine glucose lowering, weight loss, and cardiovascular protection ❤️. Caution: GI side-effects, pancreatitis risk, and MEN2 contraindication. Their role continues to expand, especially with oral semaglutide and obesity-focused agents.