medwireNews: The long-acting amylin analog cagrilintide promotes notable weight loss during 26 weeks of use, show phase 2 trial findings.
“Given its novel mechanism of action and the known heterogeneity of response to currently approved pharmacotherapies, cagrilintide presents an opportunity to expand the range of existing pharmacotherapies for weight management,” write the researchers in The Lancet.
David Lau (University of Calgary Cumming School of Medicine, Alberta, Canada) and colleagues recruited 706 people who did not have diabetes but had obesity or a BMI of at least 27 kg/m2 plus hypertension or dyslipidemia. The participants were an average age of 52 years, 62% were women, 77% were White, and their average BMI was 37.8 kg/m2.
After 26 weeks of treatment, people randomly assigned to receive cagrilintide at 0.3, 0.6, 1.2, 2.4, or 4.5 mg/week had achieved average bodyweight reductions of 6.0%, 6.8%, 9.1%, 9.7%, and 10.8%, respectively. These were all significantly larger than the average 3.0% reduction achieved by those taking placebo.
Moreover, the 10.8% reduction achieved with the highest cagrilintide dose was significantly greater than the average 9.0% reduction achieved by people assigned to take liraglutide 3.0 mg/day. These percentage reductions were equivalent to the loss of 11.5 and 9.6 kg, respectively.
With the highest cagrilintide dose, 88.7%, 53.5%, and 18.7% of people achieved weight loss of at least 5%, 10%, and 15%, respectively.
The researchers note that these analyses were based on the trial product estimand, giving results for a “hypothetical situation in which all participants had adhered to treatment.” But a treatment policy estimand (based on the intention-to-treat principle) gave similar results.
And they stress: “By contrast with placebo, reductions in weight with cagrilintide continued throughout the 26 weeks of treatment and did not appear to reach a plateau.
“As sustained weight loss is crucial for improvements in obesity-related complications, longer studies are needed to establish the full weight-loss potential of cagrilintide and determine whether weight loss is sustained long term.”
There were no changes in glycated hemoglobin or fasting glucose except in the liraglutide group, but both active treatments produced reductions in fasting insulin, triglycerides, and very-low-density cholesterol.
The adverse event rate ranged from 71% to 88% across the cagrilintide groups, compared with 81% for liraglutide and 66% for placebo. Serious adverse events occurred at corresponding rates of 2–7% compared with 4% and 3%.
Gastrointestinal events were the most frequent complaint, occurring in 41–63% of the cagrilintide groups, compared with 60% of the liraglutide group and 32% of people taking placebo. The second most common issue was injection site reactions.
“Permanent treatment discontinuation due to gastrointestinal disorders with cagrilintide was low and not dose-dependent,” observe Lau and team.
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