CagriSema reduces HbA1c, weight across T2D spectrum in REIMAGINE trials | ADA 2026

CagriSema, an investigational once-weekly fixed-dose combination of the amylin analog cagrilintide and the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, significantly lowered HbA1c and body weight versus comparators across three phase 3 trials in adults with type 2 diabetes, according to data presented at the American Diabetes Association's 2026 Scientific Sessions in New Orleans.

“While the positive effects of GLP-1 [receptor agonists] are proven, this study demonstrates how we can enhance outcomes by combining them with amylin analogs—ultimately helping patients achieve the blood glucose results they need,” Akshay B. Jain, M.D., F.R.C.P.C., senior author of the study, said in a press release. “The combination of cagrilintide and semaglutide worked better than either of those components on their own, showing us what may be the next generation of treatments for type 2 diabetes.”

The REIMAGINE 1, 2 and 3 trials each met their primary HbA1c end point and confirmatory secondary end points for body weight reduction. REIMAGINE 1 and REIMAGINE 2 results were published simultaneously in The Lancet Diabetes & Endocrinology, and REIMAGINE 3 was published in The Lancet.

REIMAGINE 1, a 40-week study of 189 treatment-naïve adults with type 2 diabetes inadequately controlled on diet and exercise, showed CagriSema 2.4 mg/2.4 mg reduced HbA1c by 1.8% and body weight by 13.8% versus placebo based on the efficacy estimand. During the presentation at ADA, lead author Vanita R. Aroda, MD, of Brigham and Women's Hospital, reported that 90% and 77% of high-dose patients hit moderate weight-reduction targets of 5%-10%, compared with 27% on placebo.

“Treating type 2 diabetes early with a combined approach offers a unique opportunity to change the course of the disease,” Aroda said in a press release. “Rather than focusing on glucose control alone, this strategy addresses weight, cardiovascular risk, and metabolic health together, with the goal of preventing long-term complications and, for some people, fundamentally resetting the trajectory of diabetes itself.”

REIMAGINE 2 is the program's largest trial, enrolling roughly 2,700 patients across 30 countries whose type 2 diabetes was inadequately controlled on metformin with or without an SGLT2 inhibitor. This was the first head-to-head comparison of CagriSema against its individual components.

Over 68 weeks, CagriSema 2.4 mg/2.4 mg reduced HbA1c by 1.91% and weight by 14.2%, outperforming semaglutide 2.4 mg (1.75% HbA1c reduction and 10.2% weight reduction) and cagrilintide alone. At ADA, senior study author Akshay Jain, M.D., clinical and research endocrinologist at Unity Healthcare in British Columbia, reported that 57% of CagriSema 2.4 mg patients achieved a composite of HbA1c at or below 6.5% plus at least 10% weight loss, and nearly one in four reached at least 20% weight reduction.

REIMAGINE 3 tested CagriSema as an add-on to basal insulin in 274 adults with long-standing disease The combination drove HbA1c reductions of more than 2 percentage points and weight loss of up to 12% with no severe hypoglycemia and without increasing insulin doses.

“These findings support a potential new therapeutic tool to effectively improve HbA1c levels well below 7% in such a challenging population of inadequately controlled basal insulin-treated type 2 diabetes with the benefit of substantial weight loss, no increase of hypoglycemia risk, and without having to increase insulin doses,” Julio Rosenstock, M.D., lead author of the study, said. “As we look to provide more solid options for people with type 2 diabetes beyond insulin-based therapies, it’s also important to note the safety and tolerability profile was consistent with previous GLP1-RA trials.”

Gastrointestinal events were the most common adverse events across all three trials, consistent with the GLP-1 RA class; discontinuation rates ranged from roughly 3% to 8.5% in CagriSema arms.

“The era of amylin is here, the future is bright, and we have a lot to look forward to,” Timothy Garvey, MD, of the University of Alabama, Birmingham, commented at the meeting.