CagriSema: Research & Studies
Scientific evidence, clinical trials, and research findings
๐TL;DR
- โข3 clinical studies cited
- โขOverall evidence level: high
- โข6 research gaps identified
Research Studies
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)
Aronne LJ, Sattar N, et al. (2025) โข New England Journal of Medicine
Phase 3 randomized trial of CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) versus placebo, semaglutide alone, and cagrilintide alone in 3,417 adults with obesity for 68 weeks.
Key Findings
- CagriSema achieved 20.4% mean weight loss vs 3.0% placebo
- Semaglutide alone achieved 14.9%; cagrilintide alone achieved 11.5%
- 60% of CagriSema participants achieved 20%+ weight loss
- 23% of CagriSema participants achieved 30%+ weight loss
- 88% with prediabetes returned to normoglycemia
Limitations: 68-week duration; no cardiovascular outcomes endpoint; higher GI adverse event rate than semaglutide alone; unequal randomization ratios
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)
Lingvay I, et al. (2025) โข New England Journal of Medicine
Phase 3 randomized trial of CagriSema versus placebo in 1,206 adults with obesity and type 2 diabetes for 68 weeks.
Key Findings
- CagriSema achieved 15.7% mean weight loss vs 3.1% placebo
- 73.5% of CagriSema group achieved HbA1c of 6.5% or less
- Significant improvements in cardiometabolic risk factors
- Lower weight loss than REDEFINE 1, consistent with T2D attenuation effect
Limitations: Placebo-controlled only (no semaglutide-alone comparator arm); 68-week duration; population limited to T2D patients
Efficacy and Safety of Co-administered Once-weekly Cagrilintide 2.4 mg with Once-weekly Semaglutide 2.4 mg in Type 2 Diabetes (Phase 2)
Frias JP, Deenadayalan S, Erichsen L, et al. (2023) โข The Lancet
Phase 2 randomized trial of CagriSema versus semaglutide alone and cagrilintide alone in 92 adults with type 2 diabetes for 32 weeks. CagriSema produced greater weight loss and glycemic control than either component alone.
Key Findings
- CagriSema produced significantly greater weight loss than either component alone
- Improved glycemic control including continuous glucose monitoring parameters
- Confirmed additive benefit of dual amylin/GLP-1 pathway targeting
- Safety profile consistent with GLP-1 agonist class
Limitations: Small sample size (n=92); 32-week duration; limited to T2D population; Phase 2 study
Unlock full research citations
Free access to all clinical studies, citations, and evidence summaries.
150+ peptide profiles ยท 30+ comparisons ยท 18 research tools
Community Experience Data
See how community outcomes align with (or diverge from) the research findings above.
Based on 15+ community reports
View community protocolsExplore research gaps across all peptides โ | View clinical trial pipeline โ
๐Research Gaps & Future Directions
- โขCardiovascular outcomes data (no CVOT completed or registered for CagriSema)
- โขLong-term safety and efficacy beyond 68 weeks
- โขHead-to-head comparison with tirzepatide for weight management
- โขEffects on body composition and lean mass preservation
- โขEfficacy in specific populations (adolescents, elderly, CKD, NASH)
- โขWeight regain patterns after CagriSema discontinuation
Research Overview#
CagriSema has been evaluated in Phase 1, Phase 2, and Phase 3 clinical trials. The REDEFINE program constitutes the pivotal Phase 3 evidence, with two large randomized controlled trials demonstrating significant weight loss and metabolic improvements in both non-diabetic obesity and obesity with type 2 diabetes.
The evidence level is classified as high based on large, well-designed Phase 3 randomized controlled trials published in the New England Journal of Medicine, with active comparator arms (REDEFINE 1 included semaglutide-alone and cagrilintide-alone groups).
Phase 2 Development#
Combination in Type 2 Diabetes#
The Phase 2 trial (Frias et al., Lancet 2023; PMID 37364590) provided the initial controlled evidence for the combination. In 92 adults with type 2 diabetes, CagriSema demonstrated greater weight loss and glycemic improvement than either cagrilintide alone or semaglutide alone over 32 weeks, establishing proof-of-concept for the dual-mechanism approach.
Continuous glucose monitoring data showed that CagriSema improved time in range and reduced glycemic variability beyond what semaglutide alone achieved, suggesting complementary effects on postprandial glucose control through amylin-mediated gastric emptying delay.
Phase 3 REDEFINE Program#
REDEFINE 1: Obesity Without Diabetes#
REDEFINE 1 (NEJM 2025; PMID 40544433) was the pivotal Phase 3 trial for the obesity indication. The trial enrolled 3,417 adults with obesity (BMI 30 or higher) or overweight (BMI 27 or higher) with at least one obesity-related complication, without diabetes. Participants were randomized in a 21:3:3:7 ratio to CagriSema, semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, or placebo for 68 weeks.
Primary endpoint (mean body weight change at 68 weeks):
- CagriSema: -20.4%
- Semaglutide alone: -14.9%
- Cagrilintide alone: -11.5%
- Placebo: -3.0%
- CagriSema vs placebo difference: -17.3 percentage points (P<0.001)
Weight loss thresholds (CagriSema):
- 10% or more: approximately 80%
- 15% or more: approximately 70%
- 20% or more: 60%
- 25% or more: approximately 40%
- 30% or more: 23%
Additional findings:
- 88% of participants with prediabetes at baseline returned to normoglycemia
- Significant improvements in waist circumference, blood pressure, lipids, and inflammatory markers
- The addition of cagrilintide to semaglutide provided an incremental 5.5 percentage points of weight loss beyond semaglutide alone
Clinical Significance of REDEFINE 1#
REDEFINE 1 is notable because it demonstrated that targeting two distinct appetite-regulatory pathways simultaneously produces meaningfully greater weight loss than either pathway alone. The 20.4% mean weight loss with CagriSema exceeds semaglutide alone (14.9% in the same trial), approaching the weight loss observed with tirzepatide 15 mg (20.9% in SURMOUNT-1) despite a different mechanism.
The inclusion of active comparator arms (semaglutide alone and cagrilintide alone) is a significant strength, allowing direct demonstration of the combination's additive benefit.
REDEFINE 2: Obesity With Type 2 Diabetes#
REDEFINE 2 (NEJM 2025; PMID 40544432) enrolled 1,206 adults with obesity and type 2 diabetes, randomized to CagriSema or placebo for 68 weeks.
Primary endpoint (mean body weight change at 68 weeks):
- CagriSema: -15.7%
- Placebo: -3.1%
- Difference: -12.6 percentage points (P<0.001)
Glycemic outcomes:
- 73.5% of CagriSema patients achieved HbA1c of 6.5% or less (vs 15.9% placebo)
- Significant HbA1c reductions from baseline
The lower weight loss in REDEFINE 2 compared to REDEFINE 1 (15.7% vs 20.4%) is consistent with the well-established observation that type 2 diabetes attenuates pharmacological weight loss responses across all GLP-1 agonist classes.
Cross-Trial Context#
| Agent | Weight Loss (Non-T2D) | Trial | Duration |
|---|---|---|---|
| CagriSema | 20.4% | REDEFINE 1 | 68 weeks |
| Tirzepatide 15 mg | 20.9% | SURMOUNT-1 | 72 weeks |
| Semaglutide 2.4 mg | 14.9% | REDEFINE 1 / STEP 1 | 68 weeks |
| Retatrutide 12 mg | ~24.2% | Phase 2 | 48 weeks |
CagriSema's weight loss is comparable to tirzepatide and exceeds semaglutide alone, though cross-trial comparisons should be interpreted cautiously due to differences in trial design, patient populations, and duration.
Evidence Quality Assessment#
| Evidence Criterion | Assessment | Details |
|---|---|---|
| Study design | Phase 3 RCTs | Double-blind, placebo- and active-controlled |
| Sample size | Large (n=3,417 in REDEFINE 1) | Adequate statistical power |
| Active comparator | Available | Semaglutide alone and cagrilintide alone in REDEFINE 1 |
| CV outcomes | Not available | No CVOT completed |
| Regulatory status | NDA filed | FDA review pending |
| Long-term data | Up to 68 weeks | Phase 3 duration |
Key Research Gaps#
-
No cardiovascular outcomes data: Unlike semaglutide alone (SELECT trial), CagriSema has no dedicated CVOT.
-
No head-to-head with tirzepatide: The most clinically relevant comparison -- CagriSema versus tirzepatide -- has not been conducted.
-
Long-term data beyond 68 weeks: Weight maintenance, durability of metabolic benefits, and long-term safety data are needed.
-
Weight regain after discontinuation: The trajectory of weight regain after stopping CagriSema has not been reported.
-
Body composition: The balance of fat versus lean mass loss has not been characterized.
Related Reading#
Frequently Asked Questions About CagriSema
Explore Further
Medical Disclaimer
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.