At the European Association for the Study of Diabetes (EASD) Annual Meeting 2025, findings were shown from the Phase IIIa REDEFINE 2 trial, assessing Novo Nordisk’s fixed-dose combination of semaglutide 2.4mg and cagrilintide 2.4mg (CagriSema) in adult patients with obesity, with a body mass index of 27kg/m² and above, type 2 diabetes (T2D), and a glycated haemoglobin (HbA1c) of 7% to 10%, who were treated with one to three oral antidiabetes drugs or lifestyle intervention. The study aimed to analyse the percentage change in body weight, additionally studying the proportion of patients who showed a body weight reduction of 5% or more, as well as assessing safety and tolerability.
The study was conducted across multiple centres, as a double-blind, placebo-controlled trial, for 68 weeks. Patients were randomised 3:1; 904 patients received CagriSema 2.4mg once a week, and 302 received placebo, with lifestyle support. Secondary endpoints included the proportion of patients with a body reduction of ≥10%, ≥15% and ≥20%, change in HbA1c, a HbA1c of 6.5% or above, and, in a continuous glucose monitoring (CGM) subgroup, time in glucose range.
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In results presented at the EASD conference by Melanie Davies CBE, MD, professor of diabetes medicine at the University of Leicester, Leicester, UK, at week 68, CagriSema achieved a significantly greater reduction in body weight than placebo (-15.7% versus -3.1%, respectively). Patients treated with CagriSema achieved more body weight reductions of ≥5% (89.7% versus 30.2%), ≥10% (74.1% versus 9.1%), ≥15% (51.6% versus 1.5%), and ≥20% (29.2% versus 0.2%) in comparison to placebo, respectively. As for HbA1c levels, patients treated with CagriSema achieved a significantly greater reduction (-2.0% points versus -0.1% points), with 80.7% reaching HbA1c ≤6.5% compared to 12.2% with placebo. Furthermore, subgroup analysis for CGM unveiled that CagriSema achieved a significantly higher time in range than placebo (89.1% versus 46.1%, respectively).
Regarding safety and tolerability, gastrointestinal adverse events were more common with CagriSema (72.5% versus 34.4%), mostly mild-to-moderate and transient. Rates of hypoglycemia were low, though level 2 and 3 episodes were slightly more frequent with CagriSema than placebo (6.0% versus 3.3% and 0.2% versus 0%, respectively).
Key opinion leaders interviewed by GlobalData expressed optimism about CagriSema, noting its benefits from targeting dual pathways. However, they emphasise that previous attempts at combining gastrointestinal hormones have raised concerns about gastrointestinal side effects like nausea and vomiting. Many expect CagriSema, alongside agents like tirzepatide, to lead the market in weight-loss therapies if efficacy and safety are confirmed in Phase III studies, but stress that issues such as route of administration, patient preferences, economics, and real-world availability will influence uptake.
The consensus is that while the mechanism is compelling and trial results are encouraging, ultimate adoption will depend on practical considerations in clinical practice.
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By GlobalDataOverall, CagriSema demonstrated weight loss and glycemic benefits in people with type 2 diabetes and overweight or obese, reinforcing its potential as a promising dual-agonist therapy pending further validation in ongoing Phase III trials. According to GlobalData’s Pharma Intelligence Center, there are 35 Phase III candidates, 94 Phase II candidates, and 111 Phase I candidates for obesity globally.
