Side by side

1. 1.Activates GIP and GLP-1 receptors, which together reduce appetite, slow gastric emptying and improve glucose-dependent insulin release.
2. 2.Adds glucagon-receptor activation, which increases energy expenditure and fat oxidation — the main difference from dual agonists such as tirzepatide.
3. 3.Glucagon activity also drives hepatic glucose output, which is why the net effect on blood glucose depends on the balance between the three receptors.
4. 4.Liver fat falls measurably in imaging sub-studies, consistent with increased hepatic fat oxidation.

• Obesity without diabetes (phase 2)
• Type 2 diabetes (phase 2)
• Fatty liver disease and liver fat content
• Obstructive sleep apnoea and knee osteoarthritis (later-stage trials)
• Cardiovascular and kidney outcomes (planned)

• Mean weight loss of up to about 24% at 48 weeks with the 12 mg dose in a phase 2 trial
• HbA1c reductions of up to about 2 percentage points in type 2 diabetes
• Large reductions in liver fat in imaging sub-studies
• Dose-related increases in resting heart rate
• High rates of gastrointestinal side effects, with more discontinuations at higher doses

• Nausea, vomiting, diarrhoea and constipation — the most common reason for stopping
• Reduced appetite and food intake
• Increased resting heart rate
• Gallbladder events
• Pancreatitis and thyroid effects are class-level concerns but not yet characterised for this drug
• Injection-site reactions

Research context only — retatrutide is not available outside clinical trials. The published phase 2 trial escalated weekly subcutaneous doses through 2 mg, 4 mg, 8 mg and 12 mg over 48 weeks with a maintenance period. Results from later-stage trials have not yet been reported.

Research context only