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Cag5.0
Cagrilintide Research
Too few graded studies
30 peer-reviewed studies
What the evidence says
Too few graded studies
Cagrilintide doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
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 30 studies · 4 meta-analyses · 10 RCTs · 44,486 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
Too few graded studies27 studies
Safety profile
Too few graded studies10 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
Too few graded studies9 studies
Active research area
30 studies in the last 5 years · Latest meta-analysis: 2026
20212026
1Meta-Analysis2026
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: Nearly all studied interventions were more effective than placebo and/or LI in reducing weight.
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: Cagrilintide and CagriSema achieved clinically meaningful weight loss with favorable cardiometabolic effects and acceptable tolerability, supporting their role as emerging options in obesity pharmacotherapy.
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: Importantly, it demonstrates superior efficacy to both cagrilintide and semaglutide, highlighting its therapeutic potential.
Khan BW, Agha SA, Qamar I, Khattak MH, Rehman A, Qazi TI, Siddiqui SA, Zeeshan N, Khan UZ, Bibi H, Khan MF, Khan HW, Mian AM, Rafay MA. · Naunyn-Schmiedeberg's archives of pharmacology (2026)
CagriSema produced significantly greater weight loss than semaglutide (MD = -7.58 kg; 95% CI = -10.30 to -4.86; p < 0.00001), cagrilintide (MD -9.24 kg; 95% CI -10.46 to -8.02, p < 0.00001), and placebo (MD = -13.99 kg; 95% CI = -18.38 to -9.61; p < 0.00001).
Adverse events were primarily gastrointestinal and injection-site reactions, with no increase in serious adverse events.
CagriSema provides substantial and clinically meaningful weight reduction with a favorable safety profile.
In plain English: Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD.
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: 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.
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).
In plain English: Glucagon-like peptide-1 receptor agonists demonstrate substantial weight loss in adults without diabetes, with an expanding range of therapeutic options, including oral and multiagonist therapies.
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.
In plain English: CagriSema presents clinically relevant reductions in BP across a wide range of participant subgroups, including those with resistant hypertension.
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: Amylin-based therapies represent a promising addition to the evolving treatment landscape of obesity.
Alhazmi A et al. · Diabetes, obesity & metabolism (2026)
Amylin-based therapies represent a promising addition to the evolving treatment landscape of obesity.
Their emerging efficacy as both standalone and combination therapies supports a multi pathway approach to addressing the biological complexity and heterogeneity of the disease.