REDEFINE 2
Trial question
What is the effect of cagrilintide/semaglutide in patients with obesity and T2DM?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
47.0% female
53.0% male
N = 1206
1206 patients (569 female, 637 male).
Inclusion criteria: adult patients with obesity and T2DM.
Key exclusion criteria: previous surgical or pharmacologic treatment for obesity within 90 days before screening; clinically significant or severe hypoglycemia within 6 months before screening or history or hypoglycemia unawareness; renal impairment with eGFR < 30 mL/min/1.73 m²; uncontrolled and potentially unstable diabetic retinopathy or maculopathy.
Interventions
N=904 cagrilintide/semaglutide (cagrilintide/semaglutide 2.4/2.4 mg once weekly plus lifestyle intervention for 68 weeks).
N=302 placebo (matching placebo plus lifestyle intervention for 68 weeks).
Primary outcome
Mean reduction in body weight at week 68
13.7%
3.4%
13.7 %
10.3 %
6.8 %
3.4 %
0.0 %
Cagrilintide/semaglutide
Placebo
Significant
increase ▲
NNT = 9
Significantly greater reduction in mean body weight at week 68 (13.7% vs. 3.4%; MD 10.4, 95% CI 9.5 to 11.2).
Secondary outcomes
Significant increase in the percentage of patients achieving a weight reduction of ≥ 5% at week 68 (83.6% vs. 30.8%; AD 52.8%, 95% CI 46.7 to 58.9).
Significantly greater reduction in mean glycated hemoglobin level at week 68 (1.8% vs. 0.4%; MD 1.4, 95% CI 1.2 to 1.6).
Significantly greater reduction in waist circumference at week 68 (11.9 cm vs. 3.6 cm; AD 8.3 cm, 95% CI 7.3 to 9.3).
Safety outcomes
No significant difference in serious adverse events.
Significant difference in gastrointestinal adverse events (72.5% vs. 34.4%).
Conclusion
In adult patients with obesity and T2DM, cagrilintide/semaglutide was superior to placebo with respect to mean reduction in body weight at week 68.
Reference
Melanie J Davies, Harpreet S Bajaj, Christa Broholm et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025 Jun 22. Online ahead of print.
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