Research Summary

Cagrilintide–Semaglutide Reduced HbA1c vs Placebo in Early-Stage Type 2 Diabetes

Anthony Calabro, MA

Key Highlights

  • Once-weekly cagrilintide–semaglutide 2.4 mg each reduced HbA1c by an estimated mean −1.8 percentage points at week 40 vs −0.1 percentage points with placebo.
  • Cagrilintide–semaglutide 1 mg each also reduced HbA1c vs placebo, with an estimated treatment difference of −1.3 percentage points.
  • Bodyweight decreased by an estimated −13.8% with cagrilintide–semaglutide 2.4 mg each and −11.8% with cagrilintide–semaglutide 1 mg each vs −1.4% with placebo.
  • Most adverse events were mild or moderate and gastrointestinal-related.

Cagrilintide–semaglutide was superior to placebo for reducing HbA1c in adults with early-stage type 2 diabetes inadequately controlled with diet and exercise, according to findings from the randomized, double-blind phase 3a REIMAGINE 1 study published in The Lancet Diabetes & Endocrinology.

Cagrilintide–semaglutide, also known as CagriSema, is a once-weekly combination of cagrilintide, an amylin receptor agonist, and semaglutide, a GLP-1 receptor agonist. Researchers evaluated the efficacy and safety of 2 dose levels of the combination therapy over 40 weeks.

REIMAGINE 1 was conducted at 42 sites in 6 countries, including university hospitals, healthcare centers, research centers, and other sites. Adults aged 18 years or older with type 2 diabetes inadequately controlled with diet and exercise were randomly assigned to once-weekly subcutaneous cagrilintide–semaglutide 2.4 mg each, cagrilintide–semaglutide 1 mg each, or placebo.

Randomization was performed using a web-based system and stratified by screening HbA1c <8.5% and participation in the MRI substudy. Participants, care providers, investigators, and outcome assessors were masked within dose level, and all participants received visually identical injections. The primary endpoint was the change in HbA1c from baseline to week 40 in the full analysis set. Safety was assessed among all participants who received at least 1 dose of the trial product, and the change in body weight from baseline to week 40 was a prespecified secondary endpoint.

Study Findings

Between March 19 and December 5, 2024, investigators screened 294 individuals and randomly assigned 189 participants to cagrilintide–semaglutide 2.4 mg each (n = 62), cagrilintide–semaglutide 1 mg each (n = 63), or placebo (n = 64). Overall, 103 participants were male, 86 were female, 147 were White, and 26 were Asian. Baseline mean HbA1c was 7.8%, and mean BMI was 35.2 kg/m².

The estimated mean HbA1c change at week 40 was −1.8 percentage points with cagrilintide–semaglutide 2.4 mg each, −1.5 percentage points with cagrilintide–semaglutide 1 mg each, and −0.1 percentage points with placebo. The estimated treatment difference was −1.7 percentage points for cagrilintide–semaglutide 2.4 mg each vs placebo (95% CI, −2.0 to −1.3; P < .0001) and −1.3 percentage points for cagrilintide–semaglutide 1 mg each vs placebo (95% CI, −1.8 to −0.9; P < .0001).

Cagrilintide–semaglutide was also superior to placebo for estimated mean relative change in bodyweight from baseline to week 40. Bodyweight decreased by −13.8% with cagrilintide–semaglutide 2.4 mg each vs −1.4% with placebo, corresponding to an estimated treatment difference of −12.4 percentage points (95% CI, −14.7 to −10.1; P < .0001). With cagrilintide–semaglutide 1 mg each, bodyweight decreased by −11.8%, with an estimated treatment difference vs placebo of −10.4 percentage points (95% CI, −12.9 to −8.0; P < .0001).

Adverse events occurred in 49 of 62 participants receiving cagrilintide–semaglutide 2.4 mg each, 47 of 63 receiving cagrilintide–semaglutide 1 mg each, and 42 of 64 receiving placebo. Most adverse events were mild or moderate and gastrointestinal-related.

Clinical Implications

According to the study authors, these findings support cagrilintide–semaglutide as a potential novel and effective therapeutic intervention for people with early-stage type 2 diabetes. The authors also stated that the safety profile was consistent with the GLP-1 receptor agonist class and previous safety data for cagrilintide.

Expert Commentary

“In a population of people with early-stage type 2 diabetes inadequately controlled with diet and exercise, cagrilintide–semaglutide was superior to placebo in reducing HbA1c, with a safety profile consistent with the GLP-1 receptor agonist class and previous safety data for cagrilintide,” the researchers concluded.

Reference
Aroda VR, Buzzetti R, Dalskov SM, et al. Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study. Lancet Diabetes Endocrinol. Published online June 7, 2026. doi:10.1016/S2213-8587(26)00126-9.