Amylin Analogue Leads to Significant Weight Loss in Obese Adults

NEW YORK (Reuters Health) – Treatment with cagrilintide in overweight or obese adults led to significant reductions in bodyweight and was well tolerated in a phase-2 clinical trial of the new amylin agent.

Amylin, a pancreatic beta-cell hormone that is secreted with insulin in response to food intake, functions as a satiety signal.

Cagrilintide is a long-acting amylin analogue previously shown to reduce food intake and bodyweight in a dose-dependent manner. The phase-2 study set out to determine the optimal dose for weight management.

A total of 706 adults with a BMI of at least 30, or at least 27 with hypertension or dyslipidemia, were randomly allocated to subcutaneous self-injections of once-weekly cagrilintide at doses of 0.3, 0.6, 1.2, 2.4 or 4.5 mg, once-daily liraglutide at a dose of 3.0 mg, or placebo.

The trial had a 26-week treatment period, including a dose-escalation period of up to six weeks, and a six-week follow-up period off treatment. All participants were counseled about diet and physical activity.

All doses of cagrilintide provided significantly greater weight loss than placebo, Dr. David Lau of the University of Calgary, in Canada, and colleagues report in The Lancet. Weight loss from baseline to week 26 with cagrilintide ranged from 3.0% to 7.8% (P<0.001). Weight loss was also greater with cagrilintide 4.5 mg versus liraglutide 3.0 mg (10.8% vs. 9.0%; P=0.03).

The most common side effects were gastrointestinal disorders (nausea, constipation and diarrhea) and injection-site reactions. More participants taking cagrilintide had GI adverse events compared with placebo (41% to 63% depending on dose vs. 32%), primarily nausea (20% to 47% vs. 18%).

Summing up, the researchers say this study provides evidence that cagrilintide “led to clinically significant, dose-dependent weight loss that was greater with cagrilintide at all doses versus placebo and greater with cagrilintide 4.5 mg versus liraglutide 3.0 mg. In participants with overweight and obesity, treatment with cagrilintide was well tolerated at all tested doses.”

“The data from this study support the further clinical development of cagrilintide for weight management,” they conclude.

The authors of a linked comment in the journal agree and note that the weight loss achieved with cagrilintide is “clinically significant,” greater than that achieved with the short-acting amylin analogue pramlintide, and “deserves further examination in longer duration trials.”

Dr. Kishore Gadde with Pennington Biomedical Research Center in Baton Rouge, Louisiana, and Dr. David Allison of Indiana School of Public Health in Bloomington also note that the weight loss with cagrilintide, “assuming it is durable over longer duration, appears to be greater than that observed with orlistat and naltrexone-bupropion, approximately the same as that with liraglutide, and less than with phentermine-topiramate and semaglutide in patients with obesity without diabetes.”

The study was funded by Novo Nordisk. Several authors have financial relationships with the company.

SOURCE: and The Lancet, online November 16, 2021.

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