Amylin and Cagrilintide Study

Amylin is a pancreatic B-cell hormone that produces effects in several different organ systems. One of its best-characterized effects is the reduction in eating and body weight seen in preclinical and clinical studies.

A recent study suggests that treatment with cagrilintide in people with overweight and obesity led to significant reductions in body weight and was well tolerated. The study findings were published in the journal The Lancet on November 16, 2021.

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

• 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 (e.g., 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."

For further information:

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