CagriSema beats semaglutide on blood sugar and weight in REIMAGINE 2

Novo Nordisk announced on 2 February 2026 that CagriSema, an experimental once-weekly injection combining the amylin receptor agonist cagrilintide with the GLP-1 drug semaglutide, beat semaglutide alone on both blood sugar and weight loss in adults with type 2 diabetes in the phase 3 REIMAGINE 2 trial ^[1][2]. The company said superiority held across all tested doses ^[1].

What the trial measured

REIMAGINE 2 ran 68 weeks and enrolled 2,728 adults with type 2 diabetes that was inadequately controlled on metformin, with or without an SGLT2 inhibitor ^[1]. About 40% of participants were taking an SGLT2 inhibitor when they started ^[1]. The trial tested CagriSema at 2.4 mg/2.4 mg and at 1.0 mg/1.0 mg against semaglutide 2.4 mg and 1.0 mg, cagrilintide 2.4 mg alone, and placebo ^[1].

Using the trial's efficacy estimand — the effect if everyone stayed on treatment, regardless of dose changes — participants on CagriSema 2.4 mg/2.4 mg lowered HbA1c by 1.91 percentage points from a mean baseline of 8.2%, compared with 1.76 percentage points on semaglutide 2.4 mg ^[1]. Placebo HbA1c rose by 0.09 percentage points ^[1].

Weight results showed a wider gap. From a mean starting weight of 101 kg (about 223 pounds), the CagriSema 2.4 mg/2.4 mg group lost 14.2% of body weight versus 10.2% with semaglutide 2.4 mg and 1.5% with placebo ^[1]. In the CagriSema high-dose group, 43% of people lost at least 15% of their body weight and 24% lost at least 20% ^[1]. Novo Nordisk said no weight loss plateau was seen by week 68 ^[1].

Under the more conservative treatment-regimen estimand, which counts results regardless of whether people stuck with treatment, CagriSema 2.4 mg/2.4 mg produced a 1.80-percentage-point HbA1c drop versus 1.68 points for semaglutide 2.4 mg, and 12.9% weight loss versus 9.2% ^[1]. That is a smaller but still statistically favorable gap, and it is the number closer to what happens in real-world use, where some people stop or pause treatment.

On safety, Novo Nordisk said CagriSema "appeared to have a safe and well-tolerated profile," with gastrointestinal side effects the most common, mostly mild to moderate, and decreasing over time — a pattern the company called consistent with incretin and amylin-based therapies ^[1]. The release did not give specific rates of nausea, vomiting or treatment discontinuation. Those numbers are not yet public.

Why it matters for patients

If CagriSema eventually reaches the US market for type 2 diabetes, it would give people a fourth mechanism in the injectable category: an amylin agonist paired with a GLP-1, rather than a GLP-1 alone (semaglutide) or a dual GIP/GLP-1 (tirzepatide). Novo Nordisk's chief scientific officer, Martin Holst Lange, framed it as a possible option for people with type 2 diabetes "who also has a focus on weight loss" ^[1].

The HbA1c advantage over semaglutide in this trial was modest — 0.15 percentage points on the efficacy estimand, 0.12 on the treatment-regimen estimand ^[1]. The weight difference was larger, roughly 4 percentage points, or about 4 kg more at a 101 kg starting weight ^[1]. Whether that trade-off is worth it depends on side effects and cost, and neither the full tolerability data nor any pricing information has been released.

A key comparison is still missing: CagriSema has not yet been reported against tirzepatide. Two trials, REIMAGINE 4 (CagriSema 2.4 mg/2.4 mg versus tirzepatide 15 mg) and REIMAGINE 5 (CagriSema 1.0 mg/1.0 mg versus tirzepatide 5 mg), each enrolling about 1,000 adults over 68 weeks, are designed to answer that ^[1]. Results were not part of this announcement.

What happens next

Novo Nordisk said it will approach regulators to discuss the pathway for CagriSema in type 2 diabetes following results from REIMAGINE 1 and REDEFINE 3 ^[1]. REDEFINE 3 is an event-driven cardiovascular outcomes trial of about 7,000 adults with established cardiovascular disease and overweight or obesity ^[1]. No timeline for those readouts or for a diabetes filing was given.

Separately, CagriSema for weight management was submitted to the US FDA in December 2025 based on the REDEFINE 1 and REDEFINE 2 trials ^[1]. The company has not announced an FDA decision date.

Detailed REIMAGINE 2 results are slated for presentation at a scientific conference in 2026 ^[1]. Until then, the figures above come from a company headline release, not peer-reviewed publication.