Makindo Medical Notes

💉 Semaglutide (Wegovy / Ozempic)

• 🧠 Class / Mechanism: A GLP-1 receptor agonist that mimics the incretin hormone. Enhances insulin secretion, suppresses glucagon, slows gastric emptying, and increases satiety.
• ⚖️ Weight loss effect: Around 10–15 % reduction in body weight over 12–18 months (STEP trials).
• 🤢 Common side effects: Nausea, vomiting, bloating, diarrhoea, or constipation — especially early in treatment.
• 🇬🇧 UK notes: Wegovy® is available via specialist NHS weight-management services. Weight regain is common if discontinued.

💉 Tirzepatide (Mounjaro / Zepbound)

• 🧬 Class / Mechanism: Dual GLP-1 and GIP receptor agonist. Increases insulin sensitivity, reduces appetite, and delays gastric emptying.
• ⚖️ Weight loss effect: Average 15–22 % loss (SURMOUNT-1 trial) — greater than semaglutide in head-to-head comparisons.
• 🤢 Common side effects: GI symptoms similar to GLP-1 analogues; possible gallbladder disease or pancreatitis.
• 📋 UK status: Approved by MHRA and recommended by NICE (BMI ≥ 35 kg/m² with comorbidities). Must be prescribed in specialist settings.

🚀 Retatrutide

• 🧬 Class / Mechanism: “Triple agonist” at GLP-1, GIP, and glucagon receptors — boosting satiety and energy expenditure.
• ⚖️ Weight loss effect: Up to 24 % body weight reduction at 48 weeks (phase 3 data).
• 🤢 Common side effects: Nausea, vomiting, mild hyperglycaemia, injection-site reactions.
• 🔬 Notes: Still in development; may represent the next generation of incretin-based weight-loss therapy.

🧪 Amycretin

• 🧬 Class / Mechanism: Dual GLP-1 and amylin receptor agonist — combining incretin and amylin pathways for powerful appetite suppression.
• ⚖️ Weight loss effect: Around 24 % loss with weekly injections over 36 weeks; 13 % loss with oral formulation (early trials).
• 🤢 Common side effects: GI upset (nausea, vomiting), particularly during dose escalation.
• 🔬 Status: Experimental; phase 3 studies ongoing. May become a leading therapy if long-term safety confirmed.

💊 Orforglipron

• 🧠 Class / Mechanism: First oral, non-peptide GLP-1 receptor agonist — same pathway as semaglutide but taken as a tablet.
• ⚖️ Weight loss effect: Roughly 7 kg loss over 9 months; potentially higher at advanced doses.
• 🤢 Common side effects: Similar to injectables — nausea, vomiting, diarrhoea.
• 🚫 Status: Not yet approved in the UK; promising for easier access and adherence once licensed.

📊 Comparison Summary

💡 Clinical tip: All GLP-1–based therapies require slow dose escalation to reduce nausea. Combine pharmacotherapy with lifestyle and behavioural support for durable weight control. Monitor for gallstones, pancreatitis, and nutritional adequacy during rapid weight loss.