Cagrilintide

Cagrilintide is a synthetic peptide that is derived from the hormone amylin. It contains thirty-seven amino acids and is designed to mimic and enhance the effects of natural amylin in the body. Researchers created it to be longer acting than the native hormone.

People use cagrilintide because it is associated with reduced appetite and improved control over food intake. It is also linked to support for weight management and better regulation of post-meal blood sugar. These reported benefits have made it a subject of interest in metabolic research.

Cagrilintide has been shown in human trials to promote substantial weight loss. In a 68-week, phase 3 study in adults with overweight or obesity (without diabetes), the combination of cagrilintide and semaglutide resulted in a mean body-weight reduction of 20.4 %, compared to 3.0 % in the placebo group ¹. In a separate 68-week study involving participants with type 2 diabetes, this same combination reduced body weight by approximately 13.7 % on average and helped a large fraction of patients achieve clinically meaningful weight-loss thresholds ². Monotherapy with cagrilintide also produced meaningful weight loss: post-hoc analysis of trial data reported an average reduction of 11.8 % after 68 week ³.

In animal studies, cagrilintide lowers body weight by acting on amylin-1 and amylin-3 receptors in the brain, reducing food intake ⁴. This receptor-mediated effect supports its mechanism for appetite regulation and body-weight control. In addition, human studies show that its use can improve metabolic markers: when paired with semaglutide, cagrilintide not only reduces weight but also lowers HbA₁c in people with type 2 diabetes ⁵. Overall, cagrilintide appears to drive potent weight loss, enhanced by combination therapy, and supports better metabolic regulation.

The main negative side effects of cagrilintide in clinical human studies are predominantly gastrointestinal. In a phase 1b trial combining cagrilintide with semaglutide, about 37% of treatment-emergent adverse events were GI-related, such as nausea, diarrhea, and abdominal discomfort, with most being mild to moderate ⁶. In a large phase III study, around 72.5% of participants on the cagrilintide–semaglutide combo reported GI side effects (including nausea, vomiting, constipation) compared to 34.4% in placebo; most of these were transient ⁷.

Beyond GI issues, cagrilintide also causes injection-site reactions, fatigue, and headache ⁸. In longer dosing studies, many people developed anti-cagrilintide antibodies (up to 46–73 % by week 26), though these did not seem to affect efficacy or trigger serious allergic reactions ⁹. However, these antibodies did not appear to influence changes in body weight, and no serious allergic reactions were reported

Cagrilintide’s mechanism of action involves binding to amylin (AMY) receptors composed of the calcitonin receptor (CTR) and receptor-activity modifying proteins RAMP1 and RAMP3, especially in brainstem areas such as the area postrema and nucleus tractus solitarius, which suppresses appetite and reduces food intake ¹⁰. In mice lacking RAMP1 and RAMP3, the weight-loss and neuronal activation effects of cagrilintide are significantly diminished, showing its dependence on these receptor subtypes ¹¹. This engagement also triggers c-Fos activation in the dorsal vagal complex and lateral parabrachial nucleus, linking receptor binding to neural activity and downstream metabolic effects ¹². In conclusion, cagrilintide induces its metabolic effects by selectively activating the AMY₁R and AMY₃R in hindbrain feeding circuits, which drives appetite suppression and body-weight reduction.

Cagrilintide is an investigational amylin analogue being tested in clinical trials and is not the active ingredient of any FDA-approved drug; the FDA has warned that cagrilintide is not approved and cannot be used in compounding ¹³. In sport, GLP-1 receptor agonists, such as semaglutide and Cagrilintide , are in WADA's monitoring program to track patterns of use and determine if they provide a performance-enhancing advantage that violates the "spirit of sport" or poses a health risk. Cagrilintide, an amylin analog, is being studied in combination with semaglutide.