Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial.

Summary

In a multicenter, double-blind phase 3a RCT in Japan and Taiwan (n=331), fixed-dose cagrilintide 2.4 mg plus semaglutide 2.4 mg produced 6.5 percentage points greater mean weight loss at 68 weeks than semaglutide 2.4 mg alone. Adverse events were mainly gastrointestinal and similar between groups; discontinuations were low and one non–treatment-related death occurred in the semaglutide arm.

Key Findings

• Mean bodyweight change at week 68: −18.4% with cagrilintide–semaglutide vs −11.9% with semaglutide (ETD −6.5 percentage points; 95% CI −8.4 to −4.6; p<0.0001).
• Adverse events occurred in 87% vs 84% (combination vs semaglutide), mostly gastrointestinal, with similar profiles across groups.
• Discontinuation rates were low (10% vs 6%); one death in the semaglutide arm was deemed not treatment-related.

Clinical Implications

For adults with overweight/obesity (with or without type 2 diabetes), combining cagrilintide with semaglutide can deliver clinically meaningful additional weight loss with comparable tolerability, potentially informing escalation strategies in obesity pharmacotherapy in Asian populations.

Limitations

• Conducted in Japan/Taiwan; generalizability to broader, more diverse populations and longer-term outcomes remains to be determined.
• Industry-funded trial; duration limited to 68 weeks without long-term cardiometabolic outcome data.

Future Directions

Evaluate durability, cardiometabolic outcomes, and real-world effectiveness across diverse Asian and non-Asian populations; compare head-to-head with other advanced anti-obesity agents (e.g., tirzepatide); refine dosing/titration strategies.