“Efficacy and Safety of AM833 [Cagrilintide] for Weight Loss: A Dose-Finding Trial in Adults With Overweight/Obesity [Abstract]”, 2020-11-04 ():
Background: Native amylin is a pancreatic polypeptide involved in postprandial glucagon suppression and appetite regulation. AM833 (NNC0174–0833) [cagrilintide] is a long-acting amylin analogue that may represent a novel treatment option for weight management.
Method: This 26-week, randomized, controlled, phase 2 trial (NCT03856047) compared the effect on body weight (BW) of increasing doses (final dose: 0.3, 0.6, 1.2, 2.4, or 4.5 mg once weekly) of subcutaneous cagrilintide vs placebo (PBO) or liraglutide (lira; a glucagon-like peptide-1 receptor agonist) 3 mg once daily, along with lifestyle interventions, in adults with obesity (BMI =30 kg⁄m2) or overweight (BMI =27 kg⁄m2) with related complications, without type 2 diabetes. Change in waist circumference (WC), metabolic parameters and safety/tolerability were also assessed.
Results: At baseline, randomized subjects (n = 706; female 62%, mean age 52 years) had mean BMI 37.8 kg⁄m2, mean BW 107 kg, and mean WC 115 cm.
BW decreased progressively and dose-dependently, and had not plateaued by week 26, with mean reductions from baseline ranging 6.0–10.8% for cagrilintide 0.3–4.5 mg, vs 3.0% (PBO) and 9.0% (lira). BW reductions from baseline were greater for cagrilintide (all doses) vs PBO (estimated treatment differences [ETD]: −3.0 to −7.8%; p < 0.001), and for cagrilintide 4.5 mg vs lira (ETD: −1.8%; p < 0.05). At week 26, 88.7%, 53.5% and 18.7% of subjects on cagrilintide 4.5 mg achieved =5%, =10%, and =15% BW loss, respectively. WC reductions were greater for cagrilintide doses 1.2–4.5 mg vs PBO (ETD: −3.4 to −4.8 cm; p < 0.001).
In general, there were no statistically-significant differences in glycemic and lipid parameters between cagrilintide and PBO. The most common adverse events with cagrilintide were gastrointestinal disorders. All cagrilintide doses were well tolerated and no new safety concerns were observed.
Conclusion: In adults with overweight or obesity, treatment with cagrilintide for 26 weeks as an adjunct to lifestyle interventions showed clinically meaningful reductions in BW and WC, with an acceptable safety and tolerability profile.