Cagrilintide (AM833) is an investigational once-weekly amylin analogue from Novo Nordisk. It mimics the gut hormone amylin to slow gastric emptying and curb appetite. Paired with semaglutide as CagriSema, it is the most-watched phase 3 weight-loss combination in development. It is not approved anywhere; access is via clinical trial only.
Survodutide (BI 456906) is an investigational once-weekly dual glucagon (GCGR) and GLP-1 receptor agonist from Boehringer Ingelheim and Zealand Pharma. By hitting both receptors it aims to cut appetite and burn more energy, and it shows promising phase 2 results in obesity and liver disease (MASH). It is not approved anywhere; access is via clinical trial only.
Both peptides share an evidence grade of C. The right choice depends less on the data and more on what you're trying to do, Cagrilintide for obesity / weight management, Survodutide for obesity / weight management.
🔬 Phase 2 dose-finding trial (Lau et al., Lancet 2021; n=706) reported up to 10.8% mean weight loss at the 4.5 mg weekly dose at 26 weeks, with a dose-response across 0.3–4.5 mg. Cagrilintide alone is not being developed as a standalone weight-loss drug; the lead programme is the CagriSema combination.
🔬 REDEFINE 1 (NEJM, 2025; n=3,417) reported ~22.7% mean weight loss at 68 weeks on cagrilintide 2.4 mg + semaglutide 2.4 mg, versus ~16.1% on semaglutide alone and ~11.8% on cagrilintide alone. Phase 3 read-out, not yet approved.
🔬 REDEFINE 2 (NEJM, 2025) tested CagriSema in adults with overweight/obesity and type 2 diabetes; weight loss and HbA1c reductions were larger than semaglutide alone. Phase 2 work in T2D (Frias et al., Lancet 2023) showed similar synergy with HbA1c and body weight.
🔬 A phase 2 dose-finding trial in adults with overweight or obesity (le Roux et al., The Lancet, 2024; ~387 participants) reported dose-dependent mean weight loss of roughly 15% at 46 weeks on the highest doses, with a clear dose-response. Promising, but phase 2 — the pivotal phase 3 obesity programme is ongoing and survodutide is not approved.
🔬 A phase 2 trial in biopsy-confirmed MASH (Sanyal et al., New England Journal of Medicine, 2024) reported that up to ~83% of participants on survodutide achieved improvement in MASH versus ~18% on placebo, with reductions in liver fat. This is among the most notable phase 2 MASH signals to date, but it is a single phase 2 trial; confirmatory phase 3 work is required.
🔬 In the same phase 2 MASH trial, more participants on survodutide than placebo showed improvement in liver fibrosis without worsening of MASH. The fibrosis signal is encouraging but secondary and underpowered for firm conclusions; fibrosis endpoints are the hard test that phase 3 must confirm.
Across phase 2 and phase 3 trials, the safety profile has looked broadly similar to other gut-hormone analogues. The most common adverse events are gastrointestinal (nausea, vomiting, diarrhoea, constipation, dyspepsia), typically worst during dose escalation and easing thereafter. Injection-site reactions are reported. Hypersensitivity reactions have been observed at higher rates than with semaglutide alone in some trials. Because amylin agonism delays gastric emptying, drugs that depend on rapid absorption may be affected. Pregnancy, breastfeeding, personal or family history of medullary thyroid cancer or MEN-2, severe gastrointestinal disease, and active pancreatitis are typical exclusions in trials of this class. Long-term safety beyond the longest published follow-up (~80 weeks for the REDEFINE programme) is not yet characterised. Quality of any non-trial "cagrilintide" sold online is unknown.
In phase 2 trials the most common adverse events were gastrointestinal — nausea, vomiting, diarrhoea and constipation — typically worst during dose escalation and easing afterwards, as with the wider GLP-1 class. The distinctive safety consideration is the glucagon receptor arm: glucagon agonism can increase heart rate and, by raising blood sugar, partially offset glycaemic benefit, which is one reason trials titrate the dose slowly. Injection-site reactions are reported. Long-term cardiovascular safety, effects in people with established heart disease, and durability beyond the phase 2 windows are not yet characterised. Typical trial exclusions for this class include pregnancy and breastfeeding, personal or family history of medullary thyroid cancer or MEN-2, active pancreatitis and severe gastrointestinal disease. The quality of any non-trial 'survodutide' bought online is entirely unknown.
Both peptides share an evidence grade of C. The right choice depends less on the data and more on what you're trying to do, Cagrilintide for obesity / weight management, Survodutide for obesity / weight management.
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