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Cag5.0
Cagrilintide Research
Mostly mechanism / observational
24 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Cagrilintide studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2021–2026 with a typical study size of 1,206 participants.
Based on 24 studies · 4 meta-analyses · 9 RCTs · 59,249 total participants
Confidence
High confidence
By outcome
Weight managementIn a 26-week phase-2 trial, cagrilintide produced ~6.0-10.8% mean weight loss vs 3.0% on placebo (best at 4.5 mg) · Over ~26 weeks
Mostly mechanism / observational22 studies
Safety profile
Mostly mechanism / observational8 studies
Glucose & glycemic controlIn a type-2-diabetes phase-2 trial, cagrilintide alone lowered HbA1c ~0.9 percentage points over 32 weeks · Over ~32 weeks
Mostly mechanism / observational7 studies
Active research area
24 studies in the last 5 years · Latest meta-analysis: 2026
20212026
1Meta-Analysisn=40,731 · very large study2026
In plain English: Weight reduction mediated by current AOMs was not associated with a reduced risk of overall or site-specific obesity-associated cancer in patients with overweight or obesity, while a decreased risk of overall obesity-associated cancer was observed in coagonist users.
Li C et al. · Obesity (Silver Spring, Md.) (2026)
Compared with placebo, AOMs showed no association with the risk of overall obesity-related cancer (RR = 1.03, 95% CI: 0.78 to 1.37) or site-specific cancer.
Consistently, every 5 kg weight reduction mediated by AOMs was not associated with the risk of overall obesity-related cancer (RR = 0.97, 95% CI: 0.84 to 1.12) or site-specific cancer.
In plain English: Primary funding source American College of Physicians. (
Damen JAA, Idema DL, Vernooij RWM, Huis In 't Veld LF, Kusters MPT, Lokerse ME, de Kanter E, Spijker R, van der Braak K, Jenniskens K, Oerbekke MS, Hooft L. · Annals of internal medicine (2026)
Limitation Direct head-to-head comparisons of different treatments were limited.
Conclusion Nearly all studied interventions were more effective than placebo and/or LI in reducing weight.
Semaglutide and tirzepatide showed the most favorable results across outcomes.
In plain English: The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points...).
Garvey WT, Blüher M, Osorto Contreras CK, Davies MJ, Winning Lehmann E, Pietiläinen KH, Rubino D, Sbraccia P, Wadden T, Zeuthen N, Wilding JPH. · N Engl J Med (2025)
Pivotal phase-3a (REDEFINE 1), 68-week, double-blind, placebo- and active-controlled trial in 3,417 adults without diabetes (BMI >=30, or >=27 with a complication); CagriSema vs semaglutide alone vs cagrilintide alone vs placebo (all 2.4 mg)
CagriSema produced -20.4% mean weight loss vs -3.0% placebo at week 68 (difference -17.3 percentage points); also superior to semaglutide and cagrilintide monotherapy arms
Includes a 302-participant cagrilintide-monotherapy arm — the largest standalone-cagrilintide dataset to date
In plain English: The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points...).
Davies MJ, Bajaj HS, Broholm C, Eliasen A, Garvey WT, le Roux CW, Lingvay I, Lyndgaard CB, Rosenstock J, Pedersen SD. · N Engl J Med (2025)
Pivotal phase-3a (REDEFINE 2), 68-week, double-blind, placebo-controlled trial in 1,206 adults with overweight/obesity and type 2 diabetes (BMI >=27, HbA1c 7-10%); once-weekly CagriSema 2.4 mg each vs placebo
CagriSema produced -13.7% mean weight loss vs -3.4% placebo at week 68 (difference -10.4 percentage points)
73.5% of the CagriSema group reached HbA1c <=6.5% vs 15.9% placebo
In plain English: Supplementary information The online version contains supplementary material available at 10.1007/s40200-026-01942-3.
Rao H, Kumar S, Ali SME, Asif HM, Kumar M, Kumar L, Raja A. · Journal of diabetes and metabolic disorders (2026)
The primary outcome was percent change in body weight.
Cagrilintide significantly reduced percent body weight versus placebo (mean difference - 6.08%, 95% CI - 8.02 to - 4.14), as did CagriSema (- 5.98%, 95% CI - 10.64 to - 1.32).
Both interventions significantly reduced absolute body weight.
In plain English: Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors.
Caruso I, Cignarelli A, Sorice GP, Perrini S, Giorgino F. · npj metabolic health and disease (2024)
Obesity-related disability-adjusted life years (DALYs) are expected to increase by approximately 40% from 2020 to 2030.
Incretin-based therapies have been associated with a body weight (BW) reduction of ≥5% in at least half of patients in most randomized controlled trials (RCT) and real-world studies (RWS).
Semaglutide and tirzepatide have also displayed a mean 60-69% 10-years relative risk reduction of T2D development.
In plain English: In this review, we will examine the efficacy and safety of the drugs marketed and others under ongoing clinical trials for the treatment of persons with obesity, as well as the main challenges faced by both healthcare professionals and patients in maintaining long-term treatment.
Rubio-Herrera MA, Mera-Carreiro S. · Medicina clinica (2025)
Beyond the necessary lifestyle changes, this new era with second-generation drugs has been able to achieve weight loss of 15-25%, close to that of bariatric surgery.
Glucagon-like peptide-1 (GLP-1) receptor agonists (RA), used as weekly injectable monotherapy or daily oral (semaglutide), achieve weight loss of 15-17%, with a good safety profile.
Tirzepatide (a dual GLP-1/GIP receptor agonist) achieves weight loss of up to 22.5% at the highest doses.
In plain English: The review protocol summary can be accessed at the
Kamrul-Hasan ABM, Khalil I, Mahajan K, Dutta D, Banerjee M, Pappachan JM. · Endocrinology, diabetes & metabolism (2026)
Primary outcome was the percent change in body weight from baseline.
Only HiD CagriSema increased AE-related discontinuation.
Conclusions Novel ABTs, such as HiD amycretin, CagriSema and eloralintide, may induce substantial short- to medium-term weight loss but may also increase GI AEs; given sparse, low-certainty data, these findings are preliminary and require confirmation in larger trials.
In plain English: The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025).
Bailey CJ, Flatt PR, Conlon JM. · Peptides (2025)
Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline.
The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities.
The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025).
Moiz A, Filion KB, Samuels AE, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ. · Annals of internal medicine (2026)
Numerically greater placebo-subtracted reductions were seen with emerging multiagonists, including -23.9% (CI, -29.3% to -18.5%) with amycretin and -22.1% (CI, -24.9% to -19.3%) with retatrutide.
Gastrointestinal adverse events (AEs) remained common (GLP-1 RA vs. placebo: 76.0% vs. 40.1%).
Discontinuation due to AEs was generally low (10.7% vs. 3.4%) but numerically higher with some oral agents.
In plain English: Cagrilintide-semaglutide at doses of 2·4 mg each and 1·0 mg each met the primary endpoint, with statistically significant and clinically relevant HbA1c reductions versus placebo when added to basal insulin-treated type 2 diabetes.
Rosenstock J et al. · Lancet (London, England) (2026)
Cagrilintide-semaglutide at doses of 2·4 mg each and 1·0 mg each met the primary endpoint, with statistically significant and clinically relevant HbA1c reductions versus placebo when added to basal insulin-treated type 2 diabetes.
These reductions were accompanied by robust bodyweight reduction and no additional risk of hypoglycaemia.
The safety profile was consistent with that of the GLP-1 receptor agonist class and previous safety data for cagrilintide.
The proportion of participants reaching BP targets at week 68 was 63.0% and 32.0% for CagriSema and placebo, respectively.
The proportion of participants with resistant hypertension at baseline (n=167) that reached BP targets at week 68 was 42.0% and 29.3% for CagriSema and placebo, respectively (odds ratio, 1.7 [95% CI, 0.7-4.4]).
Among participants who used antihypertensive medication during the study, 39.6% in the CagriSema group decreased or stopped treatment from week 0 to week 68 versus 18.8% with placebo.
In plain English: Such insight will also be important to understand how amylin and sCT analogues synergize with other molecules as part of dual or triple agonist therapies for obesity, especially the glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide, which has been shown to synergistically lower body weight with cagrilintide (CagriSema) in clinical trials.
Hankir MK, Le Foll C. · Biochimie (2025)
While the caudal hindbrain was originally implicated as a major site of action in this regard, it is becoming increasingly clear that amylin recruits numerous central nervous system pathways to exert multifaceted effects on food intake.
In plain English: Understanding how amylin-based therapies dissociate weight-loss efficacy from gastrointestinal intolerance may guide the rational design of next-generation anti-obesity drugs with improved clinical utility.
Fischer SL, Borner T. · Pharmacological research (2026)
This distinction may be critical for understanding both efficacy and tolerability, as calcitonin receptor engagement, exposure kinetics, and downstream neural circuit recruitment may influence whether reduced food intake reflects physiological satiation or aversive signaling.
In this review, we summarize the biology of amylin signaling, the historical development of amylin-based therapeutics, and the emerging clinical landscape of long-acting amylin analogs.
We place particular emphasis on the tolerability profile of this drug class and discuss how receptor pharmacology, hindbrain and parabrachial circuitry, species differences, and pharmacokinetic exposure may shape nausea, malaise, and emesis.
In plain English: The mean change in bodyweight from baseline to week 32 (CagriSema: -15·6%; semaglutide: -5·1%; cagrilintide: -8·1%) was greater with CagriSema versus both semaglutide and cagrilintide.
Phase-2, double-blind, active-controlled trial in 92 adults with type 2 diabetes on metformin ± SGLT2 inhibitor; once-weekly CagriSema vs semaglutide vs cagrilintide (all escalated to 2.4 mg) over 32 weeks
Cagrilintide monotherapy lowered weight and HbA1c less than the combination; mild/moderate GI events were most common, with no level 2-3 hypoglycaemia and no fatal events
In plain English: Together, these developments signify a transformative era in obesity care where pharmacotherapy is a powerful and evidence-based tool that, in many cases, approaches the efficacy and metabolic benefits traditionally associated with bariatric surgeries.
Atal S et al. · Indian journal of pharmacology (2026)
It significantly increases the risk of type 2 diabetes, cardiovascular disease, metabolic-associated fatty liver disease, and mental health disorders. 2022 data reveal that nearly 3 billion individuals worldwide were living with either obesity or overweight.
The emerging pipeline is even more promising.
It has new dual and triple combinations such as CagriSema, Survodutide, and Retatrutide for better efficacy and metabolic outcomes, as well as long-acting and oral formulations, which will improve adherence and accessibility.
In plain English: At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% for cagrilintide 1·2 mg and 17·1% for cagrilintide 2·4 mg vs 9·8% for pooled placebo)... all in combination with semaglutide 2·4 mg.
Enebo LB, Berthelsen KK, Kankam M, Lund MT, Rubino DM, Satylganova A, Lau DCW. · Lancet (2021)
Phase-1b, randomised, placebo-controlled, multiple-ascending-dose trial in 95 treated adults with overweight/obesity; once-weekly subcutaneous cagrilintide 0.16-4.5 mg co-administered with semaglutide 2.4 mg over 20 weeks
Proof of concept for the CagriSema combination: ~15-17% weight loss at the 1.2/2.4 mg doses vs ~9.8% pooled placebo (all with semaglutide)
Cagrilintide half-life 159-195 h; exposure proportional to dose and did not affect semaglutide exposure; 37% of adverse events were GI disorders, most mild-to-moderate