Once-weekly cagrilintide Shows Promising Results for Treatment of Obesity: Lancet

Cagrilintide is a long-acting amylin analogue under investigation for weight management. Prof David C W Lau, MD and his team conducted a study to assess the dose-response relationship of cagrilintide regarding the effects on body weight, safety, and tolerability.

It was a multicentre, randomized, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial at 57 sites in ten countries. The researchers included a total of 706 participants without diabetes, with a body-mass index of at least 30 kg/m2 or at least 27 kg/m2 with hypertension or dyslipidaemia. Participants were randomly assigned to either subcutaneous self-injections of once-weekly cagrilintide (0·3, 0·6, 1·2, 2·4, or 4·5 mg), once-daily liraglutide 3·0 mg, or volume-matched placebo (for six placebo groups). They received treatment for 26 weeks followed by a dose-escalation period of up to 6 weeks and a 6-week follow-up period without treatment. The major outcome assessed was the percentage change in body weight from baseline to week 26. researchers also assessed the safety profile in all participants who received at least one dose of randomized treatment.

Key Findings of the Study were:

• Upon analysis, the researchers observed that permanent treatment discontinuation (n=73) occurred similarly across treatment groups, mostly due to adverse events (n=30).
• They found that the mean percentage weight reductions from baseline were greater with all doses of cagrilintide (0·3–4·5 mg, 6·0%–10·8% [6·4–11·5 kg]) when compared with placebo (3·0% [3·3 kg]; estimated treatment difference range 3·0%–7·8%).
• They also noted that weight reductions were greater with cagrilintide 4·5 mg than in liraglutide 3·0 mg (11·5 kg vs 9·6 kg; estimated treatment difference 1·8%).
• They observed similar weight loss reductions with the treatment policy estimand.
• They reported that the most frequent adverse events were gastrointestinal disorders (eg nausea, constipation, and diarrhoea) and administration-site reactions.
• They noted that more participants receiving cagrilintide 0·3–4·5 mg had gastrointestinal adverse events compared with placebo (41%–63% vs 32%), primarily nausea (20%–47% vs 18%).

The authors concluded, "Treatment with cagrilintide in people with overweight and obesity led to significant reductions in body weight and was well tolerated. The findings support the development of molecules with novel mechanisms of action for weight management."

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DOI: https://doi.org/10.1016/S0140-6736(21)01751-7