CagriSema and Anthropometric Treatment Targets: A New Look at REDEFINE 1

Percentage weight loss has been the standard yardstick in obesity trials for decades, but it has a well-known limitation: a given percentage doesn’t mean the same thing for every participant, and it doesn’t map cleanly onto the absolute thresholds clinicians actually use to think about cardiometabolic risk. A secondary, post hoc analysis of the REDEFINE 1 trial, published in Diabetes, Obesity and Metabolism in July 2026, takes a different approach — asking how many participants crossed fixed anthropometric targets, and whether those targets track cardiometabolic outcomes better than percentage weight loss alone.

What REDEFINE 1 tested

REDEFINE 1 is the phase 3a, 68-week trial that randomized adults without diabetes — all with a BMI of 30 kg/m² or higher, or 27 kg/m² or higher with at least one obesity-related complication — to once-weekly CagriSema (the fixed-dose cagrilintide/semaglutide combination, both components at 2.4 mg), semaglutide alone, cagrilintide alone, or placebo, each alongside a lifestyle intervention. This new analysis didn’t add new patients or a new arm; it re-examined the existing REDEFINE 1 dataset through a different lens — specifically, whether participants reached a BMI below 27 kg/m² and/or a waist-to-height ratio (WHtR) below 0.53, and how those absolute targets related to four cardiometabolic markers: normoglycemia, blood pressure, triglycerides, and HDL cholesterol.

What the analysis found

At week 68, the proportion of participants who reached both the BMI and WHtR targets was 30.3% in the CagriSema group, compared with 19.1% for semaglutide alone, 9.0% for cagrilintide alone, and 3.3% for placebo. The gap between CagriSema and the monotherapy arms held up as a consistent pattern rather than a narrow statistical margin. The researchers also compared BMI and WHtR head-to-head as predictors of the four cardiometabolic outcomes and found the two measures performed similarly — but at more stringent cutoffs, both anthropometric targets tracked cardiometabolic status more closely than percentage weight loss did.

Why this framing matters for the research literature

The interesting part of this analysis isn’t just that CagriSema produced more responders — that direction was already expected given prior REDEFINE data. It’s the argument for a different way of reporting obesity-trial outcomes generally: instead of (or alongside) “average percentage weight loss in the treatment group,” reporting “proportion of participants who crossed a clinically meaningful absolute threshold” gives a picture that’s arguably more directly tied to the cardiometabolic risk reduction that’s the actual point of the intervention. If this framing gets adopted more broadly, it could change how future amylin/GLP-1 combination trials — including ongoing work on retatrutide-based combinations — report and compare results.

It’s worth being precise about what this analysis does and doesn’t establish: it’s a secondary, post hoc look at data from a single trial population (adults without diabetes), using thresholds the authors selected for this analysis rather than a pre-registered primary endpoint. The authors themselves frame it as supporting “further validation” of target-based reporting, not as a settled conclusion. As with all findings summarized here, this is a description of published trial-level research, not guidance for any individual, and no dosing or treatment decision should be drawn from it.

Further reading

Busetto, L., Contreras, C.O., Christensen, M.H., et al. (2026). “Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1.” Diabetes, Obesity and Metabolism. PubMed: 42503495 · DOI: 10.1111/dom.71134