As blogged previously, CagriSema is the first combination treatment of an amylin analog (cagrilintide) and a GLP1 (semaglutide, aka Wegovy) that has been explored in phase 3 trials. Three trials evaluating CagriSema in people with type 2 diabetes have just been published!

In the REIMAGINE-1 study, 189 adults with early type 2 diabetes on no diabetes medication were randomly assigned to receive CagriSema 2.4mg/2.4mg, CagriSema 1mg/1mg, or placebo for 40 weeks. At the start of the study, baseline A1c (diabetes report card) was 7.8%, and BMI was 35.2. For people who took treatment as intended (efficacy estimand),

  • CagriSema 2.4mg/2.4mg: A1c reduction -1.8%, weight loss -13.8%
  • CagriSema 1mg/1mg: A1c reduction -1.5%, weight loss -11.8%
  • placebo: A1c increase +0.1%, weight loss -1.4%

Ninety-two percent of people completed the study on treatment, which is excellent; the study allowed flexibility in dosage to find the best dose for each patient, reflecting what we do in real life practice. Both doses of CagriSema improved other metabolic health parameters including systolic blood pressure and cholesterol. The most common side effects were gastrointestinal (most commonly nausea), occuring in 53% of the CagriSema 2.4mg/2.4mg group, 44% of the CagriSema 1mg/1mg group, and 20% of the placebo group. Most of these side effects were mild to moderate and had onset during dose escalation.

The REIMAGINE-2 study, (disclosure, I am an author on this publication) provided the opportunity to compare CagriSema vs each of its components (cagrilintide and semaglutide alone), and vs placebo. We randomized 2,713 adults with type 2 diabetes on metformin and/or SGLT2 inhibitor; average age 57, baseline A1c 8.2%, baseline BMI 35.1, and baseline weight 100.9kg. These people were further along in their diabetes journey than in the trial above, with the average duration of diabetes being 8.5 years. At 68 weeks,

  • CagriSema 2.4mg/2.4mg: A1c reduction -1.9%, weight loss -14.2%
  • semaglutide 2.4mg: A1c reduction -1.75%, weight loss -10.2%
  • cagrilintide 2.4mg: A1c reduction -0.8%, weight loss -8.4%
  • CagriSema 1mg/1mg: A1c reduction -1.82%, weight loss -12%
  • semaglutide 1mg: A1c reduction -1.54%, weight loss -7.5%
  • placebo: A1c increase +.09%, weight loss -1.5%

So, there was a little better diabetes control with CagriSema vs semaglutide alone, and substantial (about 4-4.5%) additional weight loss. Cagrilintide 2.4mg alone also gave a nice reduction in both A1c and weight – highly relevant, as cagrilintide is being explored as a stand-alone treatment for weight management. In terms of tolerability, there was a little more in terms of GI side effects with combination CagriSema vs semaglutide alone; cagrilintide alone was quite well tolerated. At the end of the study, 88% of participants were taking the treatment, and again here the dose was flexible, to find the right dose for each patient.

In the REIMAGINE-3 study, looked at 274 people with a longer duration of diabetes (14.9 years on average) who were taking insulin, and randomized them to receive CagriSema 2.4mg/2.4mg , 1mg/1mg , or placebo. Baseline A1c was 8.8%, BMI 31.6, and 45.6% identified as Asian ethincity. At 40 weeks,

  • CagriSema 2.4mg/2.4mg: A1c reduction -2.3%, weight loss -12%
  • CagriSema 1mg/1mg: A1c reduction -2.1%, weight loss -10.4%
  • placebo: A1c reduction -0.7%, weight gain +1.1%

The average insulin dose decreased by 2 units in each CagriSema group, and increased by 18 units in the placebo group – in other words, CagriSema facilitated better diabetes control with substantially lower insulin needs than the placebo group. As for the other two studies, most people (86-89%) on cagrisema completed treatment (at variable doses) , and gastrointestinal side effects were most common, and more common with higher dose CagriSema.

BOTTOM LINE: CagriSema has proven beneficial to improve A1c, weight, and metabolic health in people across the spectrum from very early type 2 diabetes, to people with a long history of diabetes on insulin therapy. It will be exciting to see what other health benefits may come to fruition with CagriSema therapy in people with obesity with or without diabetes, including ongoing studies in cardiovascular disease, chronic kidney disease in type 2 diabetes, peripheral neuropathy, and for potential bone preservation during weight loss.

Disclaimer: I am/have been an investigator in clinical trials of cagrilintide, semaglutide , and CagriSema.  I receive honoraria as a continuing medical education speaker and consultant from the makers of cagrilintide, semaglutide, and CagriSema (Novo Nordisk).

Share this blog post using your favorite social media link below!

Follow me on X/twitter! @drsuepedersen

Check me out on Insta! drsuepedersen

www.drsue.ca © 2026