REIMAGINE 1 reports lower A1C and weight with CagriSema than placebo

What happened

Adults managing type 2 diabetes with diet and exercise entered REIMAGINE 1 if their blood sugar remained above target. They received a weekly test product. CagriSema pairs cagrilintide, which targets amylin receptors, with semaglutide, which targets GLP-1 receptors.

This randomized phase 3a study assigned 189 participants across 42 sites in six countries. One arm received 2.4 mg apiece of cagrilintide and semaglutide, a second received 1.0 mg apiece, and the control arm received matching placebo. Treatment continued for 40 weeks. At baseline, mean A1C was 7.8% and mean BMI was 35.2.

At week 40, estimated mean A1C was 1.8 percentage points below baseline with the higher dose and 1.5 points below baseline with the lower dose. The placebo change was 0.1 point. Compared with placebo, the estimated additional reductions were 1.7 and 1.3 percentage points.

Estimated average body weight declined by 13.8% with the higher dose and 11.8% with the lower dose, compared with 1.4% for placebo. Adverse events were reported by 79%, 75% and 66% of participants, respectively. Most events were gastrointestinal and mild or moderate. Novo Nordisk funded the trial.

What it means

Random assignment in REIMAGINE 1 supports a treatment effect on two distinct measures: A1C and body weight. Both CagriSema regimens outperformed placebo for the early-treatment population enrolled. Within the three-study cluster, this is the trial for adults who entered without a glucose-lowering medicine.

The other REIMAGINE studies answer different questions. REIMAGINE 2 compared the combination with semaglutide and cagrilintide in people using metformin, sometimes with an SGLT2 inhibitor. REIMAGINE 3 added the combination to basal insulin. Reading the cluster together shows where each result fits without treating one population as a substitute for another.

What it does not mean

Because REIMAGINE 1 used placebo, it cannot show how CagriSema compares with semaglutide alone. Its 189 participants and 40-week duration are also not enough to define uncommon harms, long-term durability or cardiovascular and kidney outcomes.

The findings should not be applied automatically to people already taking several diabetes medicines, people using basal insulin or people without diabetes who are seeking obesity treatment. Average trial results also cannot predict an individual person's response or tolerability.