Results Highlight Promise of Amylin and GLP-1 Pairings as Future Options for Weight Loss and Diabetes Care

/PRNewswire/ -- Fresh global research has shown encouraging outcomes for the first injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) paired with an amylin analogue. This dual treatment improves blood sugar regulation and aids weight loss across varied groups of adults who have type 2 diabetes. Investigators shared REIMAGINE trial findings during a symposium at the 2026 Scientific Sessions of the American Diabetes Association (ADA) in New Orleans.

Amylin is a pancreatic hormone released together with insulin and is gaining attention as a target for diabetes and obesity therapies. It supports stable blood glucose and promotes satiety after meals. Synthetic amylin agonists replicate these actions and represent an emerging drug class. With rising demand for treatments addressing both weight and type 2 diabetes, scientists are examining combined use of amylin analogues and GLP-1 RAs. The REIMAGINE program tested CagriSema, which merges cagrilintide (an amylin mimic) and semaglutide (a GLP-1 RA). All REIMAGINE studies are randomized phase 3 trials assessing safety and efficacy of CagriSema in adults with type 2 diabetes.

REIMAGINE 1: CagriSema Enhanced Diabetes Control for Patients Using Only Diet and Exercise

REIMAGINE 1 is a phase 3 randomized double-blind trial that assessed safety and efficacy of CagriSema versus placebo in adults with type 2 diabetes who had not improved with diet or exercise alone. Treatment consisted of once-weekly injections for nine months, followed by an off-treatment interval to observe effects after discontinuation.

In 189 participants worldwide, a fixed-dose mix of cagrilintide and semaglutide helped lower blood glucose and reduce weight early in the disease course. It also showed potential to achieve diabetes remission with once-weekly dosing. Results appeared simultaneously in The Lancet.

"Early combined treatment for type 2 diabetes provides a distinctive chance to alter disease progression," noted Vanita R. Aroda, MD, lead study author. "Instead of glucose control in isolation, this method tackles weight, cardiovascular risk, and overall metabolic health together to avert long-term issues and, in select cases, reset the diabetes trajectory."

REIMAGINE 2: CagriSema Delivered Greater Benefits Than Its Separate Components

REIMAGINE 2 was a 68-week trial comparing CagriSema against cagrilintide alone, two doses of semaglutide, and placebo in 2,728 patients with type 2 diabetes whose glucose remained elevated on metformin with or without an SGLT2 inhibitor. Participants also had overweight or obesity.

Published in The Lancet, the study found that the fixed-dose cagrilintide-semaglutide combination reduced blood glucose more than semaglutide monotherapy, while CagriSema users achieved greater weight loss than those on current standard therapies.

"Although GLP-1 RAs produce proven benefits, this work shows how pairing them with amylin analogues can further improve results and help patients reach needed glucose targets," stated Akshay B. Jain, MD, FRCPC, senior author. "The cagrilintide-semaglutide combination outperformed either agent alone, pointing toward the next wave of type 2 diabetes treatments."

Investigators continue sub-analyses and further evaluations to clarify CagriSema effects relative to its individual parts.

REIMAGINE 3: CagriSema Produced Strong Glucose Improvements and Weight Loss in Long-Standing Diabetes on Basal Insulin

REIMAGINE 3 examined CagriSema in 274 adults with type 2 diabetes whose glucose was inadequately controlled on basal insulin with or without metformin.

The trial demonstrated that adding the fixed-dose cagrilintide-semaglutide combination yielded robust glucose reductions (HbA1c falling from 8.8 percent to 6.5 percent) and weight loss reaching 12 percent even in patients with longstanding disease already receiving basal insulin. No severe hypoglycemia occurred. Findings were published simultaneously in The Lancet.

"These data support a promising new option that can drive HbA1c well below 7 percent in this difficult basal-insulin population while delivering meaningful weight loss, preserving hypoglycemia safety, and avoiding insulin dose increases," said Julio Rosenstock, MD, lead author. "The safety and tolerability profile aligned with prior GLP-1 RA experience."

Additional REIMAGINE 3 analyses are planned along with further readouts from the overall program.

Research presentation details:

REIMAGINE 1: CagriSema as Monotherapy for Drug-Naive T2D

Vanita R. Aroda, MD
Symposium: REIMAGINE 1, 2, 3: Leveraging Amylin and GLP-1 for Type 2 Diabetes Care with CagriSema
Sunday, June 7 from 4:45-5:00 p.m. CT
Ernest N. Morial Convention Center, Great Hall A (Level 1)

Research presentation details:

REIMAGINE 2: CagriSema vs. Semaglutide or Cagrilintide in T2D on Metformin with or without SGLT2i

Akshay B. Jain, MD, FRCPC
Symposium: REIMAGINE 1, 2, 3: Leveraging Amylin and GLP-1 for Type 2 Diabetes Care with CagriSema
Sunday, June 7 from 5:00-5:15 p.m. CT
Ernest N. Morial Convention Center, Great Hall A (Level 1)

Research presentation details:

REIMAGINE 3: CagriSema Add-On for Basal Insulin-Treated T2D with or without Metformin

Julio Rosenstock, MD
Symposium: REIMAGINE 1, 2, 3: Leveraging Amylin and GLP-1 for Type 2 Diabetes Care with CagriSema
Sunday, June 7 from 5:15-5:30 p.m. CT
Ernest N. Morial Convention Center, Great Hall A (Level 1)

About American Diabetes Association's 2026 Scientific Sessions
The ADA's 2026 Scientific Sessions, the premier global diabetes research and care meeting, takes place in New Orleans from June 5-8. Thousands of physicians, scientists, and health professionals will gather in person and virtually to present new research, treatment guidance, and progress toward a diabetes cure. Attendees gain access to thousands of original presentations and engage with leading experts. Follow the conversation on social media with #ADASciSessions.

About American Diabetes Association
The American Diabetes Association (ADA) leads voluntary efforts to end diabetes and support those living with the condition. Marking 85 years of advancing discovery, the ADA works to prevent, manage, treat, and ultimately cure diabetes. More than 155 million Americans have diabetes or prediabetes. Through advocacy, programs, and education the organization serves this community. Visit diabetes.org or call 1-800-DIABETES (800-342-2383). Connect on Facebook, Spanish Facebook, LinkedIn, Instagram, and X.

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SOURCE American Diabetes Association