CagriSema got 30% of patients to a healthy weight-and-waist target

A new analysis of the REDEFINE 1 obesity trial reports that CagriSema — a weekly injection combining the amylin analogue cagrilintide with semaglutide — got 30.3% of participants down to both a normal body-mass index and a healthy waist size at 68 weeks, against 19.1% on semaglutide alone, 9.0% on cagrilintide alone, and 3.3% on placebo [s1]. The point of the paper is not a bigger weight-loss number but a different yardstick: judging obesity drugs by whether patients reach a healthy body shape, not only by the percentage they shed [s1].

The underlying trial has already been reported. REDEFINE 1 randomised 3,417 adults with obesity, or with a BMI of at least 27 plus an obesity-related complication and no diabetes, to weekly CagriSema, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo, all with lifestyle support [s1][s2]. Most participants — 2,108 of the 3,417 — were assigned to CagriSema, with 302 each to the single-drug arms and 705 to placebo [s2]. In the primary results, mean body weight fell 20.4% on CagriSema versus 3.0% on placebo — a difference of 17.3 percentage points (95% CI −18.1 to −16.6) [s2]. The trial was funded by Novo Nordisk, which makes the drug, and company employees are among the authors of both papers [s2][s1].

What the new analysis did

This post-hoc analysis, published in July, took the same participants and asked a clinical question the headline percentage does not: how many actually crossed into a lower-risk range? It scored two absolute targets — a BMI below 27 kg/m² and a waist-to-height ratio below 0.53 — and counted who hit both [s1]. On that combined measure CagriSema roughly tripled the placebo rate and outperformed semaglutide, the current standard, by about eleven percentage points [s1].

The authors then checked whether hitting those body-size targets tracked with actual metabolic health, looking at four markers: normal blood glucose, blood pressure under 130/80 mmHg, triglycerides below 1.7 mmol/L, and healthy HDL cholesterol [s1]. Both BMI and waist-to-height performed similarly as indicators of those outcomes, and at stricter cut-offs the target-based measures were better than raw percentage weight loss at flagging who had improved [s1]. The gap between the arms is instructive: cagrilintide alone got only 9.0% of patients to the combined body-size target, well short of semaglutide's 19.1% and less than a third of CagriSema's rate — consistent with the combination outperforming either component on its own [s1]. The larger implication the authors draw is a shift toward "treat to target" in obesity, the way blood pressure and cholesterol are already managed [s1].

Why the framing matters, and where it is thin

Reporting weight drugs by target rather than by average percent is more than presentation. An average of "20% lost" hides a wide spread; a target tells a patient starting well above the healthy range whether the drug is likely to get them into it at all — and for many, even a large percentage still leaves them above a BMI of 27 [s1]. Reaching both a normal BMI and a normal waist is a stiffer bar than the trial's original endpoints, and CagriSema clearing it in roughly one in three patients is the analysis's real finding [s1].

The limits are equally real. This is a secondary, post-hoc look, meaning the targets were chosen after the trial and the comparisons were not what it was powered to prove [s1]. It reports who reached a healthier body size, not whether that translates into fewer heart attacks, strokes or deaths, which no weight-loss trial in this class has yet shown for CagriSema. Tolerability also shapes who stays on treatment: gastrointestinal side effects hit 79.6% of the CagriSema group versus 39.9% on placebo in the main trial, mostly mild and transient but not trivial [s2]. And the drug is not yet approved; a target-based case for it is being made before regulators have ruled.

CagriSema sits in a fast-filling field of combination and next-generation obesity drugs, from higher-dose semaglutide to other amylin-plus-incretin pairings still in mid-stage trials. The useful contribution here is methodological — a reminder that the honest question about any of them is not how much weight came off on average, but how many people it actually moved into a healthier range. This article describes trial findings and is not medical advice.