CagriSema (Cagrilintide + Semaglutide)

Structure: A fixed-dose co-formulation rather than two separate injections. Cagrilintide is a long-acting amylin analog that also engages the calcitonin receptor. Semaglutide is the GLP-1 receptor agonist sold as Wegovy and Ozempic. The rationale is that amylin and GLP-1 suppress appetite through separate routes, so combining them should do more than raising either alone.

Status:

• REDEFINE 1, the pivotal Phase 3 trial, has reported and is published in the New England Journal of Medicine (Garvey et al., 2025).
• Not approved by the FDA, EMA, TGA or any other regulator at the time of writing.
• No legitimate supply exists. Anything sold under the name is grey-market material.

What REDEFINE 1 actually showed:

• 3,417 participants with overweight or obesity, randomised across four arms, 68 weeks.
• Mean weight change was 20.4% on CagriSema against 3.0% on placebo (treatment-policy estimand). The trial-product estimand, which asks what happens to people who stay on treatment, gives 22.7%.
• The individual arms are the useful part for judging what the amylin component adds: semaglutide alone reached 16.1%, cagrilintide alone 11.8%.
• So the combination added roughly 4 to 6 percentage points over a maximal semaglutide dose, depending on the estimand. Real, and a long way short of doubling it.

Dosage:

• Trial dosing was cagrilintide 2.4mg with semaglutide 2.4mg once weekly, reached by slow escalation over 16 weeks rather than started at target.
• There is no approved label and therefore no authoritative dosing guidance.

Key notes:

• Gastrointestinal load is the real trade-off. GI adverse events affected 79.6% of the CagriSema group against 39.9% on placebo. Two drugs that both slow gastric emptying and both act on the area postrema produce a heavier burden than either alone, and this is the main reason people stop.
• The muscle-sparing story does not survive the data. A DXA substudy of 252 participants, presented at ObesityWeek 2025 and not yet published in a journal, split the weight loss by tissue: CagriSema 66.9% fat and 33.1% lean, semaglutide alone 69.7% and 30.3%, cagrilintide alone 62.9% and 37.1%. The amylin-containing arms lost proportionally more lean tissue, not less. See Does eloralintide protect muscle better than a GLP-1?.
• Do not stack it with another amylin or another GLP-1. It already contains one of each. Adding eloralintide, more cagrilintide, or a second incretin duplicates a mechanism and adds side effects without adding effect.
• Rate of loss is the thing to manage. Twenty percent over 68 weeks averages under 0.5% per week, which is reasonable. Most people lose considerably faster in the first months, and that is where lean mass is lost. High protein intake and resistance training remain the interventions with actual evidence behind them.

Monitoring: Fasting glucose, HbA1c, fasting insulin and HOMA-IR at baseline and every 8 to 12 weeks. Electrolytes if food intake drops sharply. Anyone using exogenous insulin or a sulfonylurea alongside it needs a dose reduction and daily glucose monitoring, because the amylin component blunts glucagon counter-regulation.