CagriSema in Clinical Trials: What Patients Should Know

Obesity and type 2 diabetes often fuel each other, making long-term health management difficult. Lifestyle changes remain the foundation, but medications are increasingly important for meaningful results.

Two recent New England Journal of Medicine (NEJM) studies tested an investigational drug combination: cagrilintide plus semaglutide, known as CagriSema. This therapy is not FDA approved and is still being studied, but the results are generating excitement. For patients, it raises important questions: how does this approach compare with current major therapies such as semaglutide and tirzepatide?

Understanding the Medications

Semaglutide

Semaglutide is a GLP-1 receptor agonist. It reduces appetite, slows stomach emptying, improves blood sugar, and lowers cardiovascular risk. It is currently approved for both type 2 diabetes and obesity at higher doses.

Cagrilintide

Cagrilintide is an amylin analogue. Amylin is a hormone that promotes satiety and helps regulate eating. Used alone, it supports weight reduction, though less dramatically than semaglutide.

The CagriSema Combination

Together, semaglutide and cagrilintide target complementary hormonal pathways. This dual mechanism enhances appetite suppression, metabolic balance, and weight reduction. The approach is similar in concept to tirzepatide, which activates both GLP-1 and GIP pathways.

The REDEFINE 1 Trial: Patients with Obesity Without Diabetes

The REDEFINE 1 trial studied individuals with obesity or overweight plus related health complications, but without diabetes.

• Participants: Over 3,400 adults.
• Results: Average weight loss was 20% with CagriSema compared with 3% with placebo.
• High-Level Results: Many reached reductions of 20–30% body weight, levels usually only seen with bariatric surgery.
• Side Effects: Nearly 80% experienced gastrointestinal symptoms, again mild-to-moderate and often short-lived.

Patient Perspective

For patients without diabetes, CagriSema produced surgery-level weight loss, far exceeding semaglutide alone. These results appear similar to tirzepatide, which has also achieved 20%+ weight loss in obesity trials.

The REDEFINE 2 Trial: Patients with Type 2 Diabetes

Published June 2025, the REDEFINE 2 trial investigated adults with both obesity and type 2 diabetes.

• Participants: Over 1,200 patients.
• Results: Patients on CagriSema lost 14% body weight compared with 3% on placebo after 68 weeks.
• Blood Sugar: About 75% achieved HbA1c ≤6.5%, versus only 16% on placebo.
• Side Effects: About 73% experienced gastrointestinal symptoms (nausea, diarrhea, or constipation), mostly mild and temporary.

Patient Perspective

For people with type 2 diabetes, CagriSema offered stronger weight and glucose benefits than typically seen with semaglutide alone. Results may approach the effectiveness of tirzepatide in diabetes studies, though direct comparisons are not yet available.

Comparison with Current Therapies

Semaglutide Alone

• Produces about 15% weight loss in non-diabetic obesity trials.
• Improves blood sugar and reduces cardiovascular risk.
• CagriSema shows greater weight loss than semaglutide alone in both NEJM studies.

Tirzepatide

• A dual GIP and GLP-1 agonist.
• Achieves 20%+ weight loss in non-diabetic obesity trials.
• Strongly lowers HbA1c in type 2 diabetes.
• CagriSema results appear comparable to tirzepatide, though no head-to-head study exists yet.

Where CagriSema May Fit

• Could become a next-generation therapy if approved.
• May offer an option for patients not responding fully to semaglutide or tirzepatide.
• Still investigational. Not yet FDA approved.

Why Holistic, Individualized Care Matters

Medication alone does not solve obesity or diabetes. Weight and metabolic health are shaped by diet, sleep, stress, cardiovascular risk, and hormonal balance. At our practice in Montgomery County, Maryland, we provide personalized, holistic care that addresses these interconnected factors.

For some patients, semaglutide is the right fit. For others, tirzepatide may offer stronger results. In the future, if CagriSema becomes available, it could add another valuable option. What matters most is a thoughtful approach tailored to the individual patient’s needs.

Takeaway

The NEJM studies highlight CagriSema as a powerful new tool, capable of producing surgery-level weight loss in some patients. Compared to semaglutide alone, results are stronger. Compared to tirzepatide, outcomes appear similar, though head-to-head trials are still needed. For patients, these advances may expand the options for long-term health and metabolic control.

Dr. Tashko

References:

1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT, Blüher M, Osorto Contreras CK, et al. The New England Journal of Medicine. 2025;393(7):635-647. doi:10.1056/NEJMoa2502081.
2. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. Davies MJ, Bajaj HS, Broholm C, et al. The New England Journal of Medicine. 2025;393(7):648-659. doi:10.1056/NEJMoa2502082.
3. Efficacy and Safety of Co-Administered Once-Weekly Cagrilintide 2·4 Mg With Once-Weekly Semaglutide 2·4 Mg in Type 2 Diabetes: A Multicentre, Randomised, Double-Blind, Active-Controlled, Phase 2 Trial. Frias JP, Deenadayalan S, Erichsen L, et al. Lancet (London, England). 2023;402(10403):720-730. doi:10.1016/S0140-6736(23)01163-7.

About Dr. Gerti Tashko, MD

Dr. Gerti Tashko, MD, is an endocrinologist in Montgomery County, Maryland. He is uniquely quadruple board-certified in endocrinology, lipidology, hypertension, and obesity medicine. His practice delivers root-cause-focused metabolic and endocrine care, available virtually and in person. He uses advanced diagnostics, personalized nutrition, and preventive medicine to improve long-term health.