SELECT
Trial question
What is the role of semaglutide in patients with preexisting CVD and overweight or obesity but without diabetes?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
28.0% female
72.0% male
N = 17604
17604 patients (4872 female, 12732 male).
Inclusion criteria: patients, aged ≥ 45 years, with preexisting CVD and a BMI ≥ 27 kg/m² but no history of diabetes.
Key exclusion criteria: MI, stroke, hospitalization for unstable angina pectoris; TIA within the past 60 days prior to the day of screening; history of T1DM or T2DM; history or presence of chronic pancreatitis.
Interventions
N=8803 semaglutide (initiated at 0.25 mg SC once weekly, then titrated every 4 weeks (0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) to the maintenance dose of 2.4 mg once weekly by week 16).
N=8801 placebo (matching placebo once weekly).
Primary outcome
CV death, nonfatal MI, or nonfatal stroke
6.5%
8%
8.0 %
6.0 %
4.0 %
2.0 %
0.0 %
Semaglutide
Placebo
Significant
decrease ▼
NNT = 66
Significant decrease in CV death, nonfatal MI, or nonfatal stroke (6.5% vs. 8%; HR 0.8, 95% CI 0.72 to 0.9).
Secondary outcomes
No significant difference in CV death (2.5% vs. 3%; HR 0.85, 95% CI 0.71 to 1.01).
Significant decrease in first occurrence of CV death or hospitalization or an urgent medical visit for HF (3.4% vs. 4.1%; HR 0.82, 95% CI 0.71 to 0.96).
Significant decrease in death from any cause (4.3% vs. 5.2%; HR 0.81, 95% CI 0.71 to 0.93).
Safety outcomes
No significant difference in serious gastrointestinal disorders.
Significant differences in serious adverse events (33.4% vs. 36.4%), adverse event leading to discontinuation of trial drug (16.6% vs. 8.2%).
Conclusion
In patients, aged ≥ 45 years, with preexisting CVD and a BMI ≥ 27 kg/m² but no history of diabetes, semaglutide was superior to placebo with respect to CV death, nonfatal MI, or nonfatal stroke.
Reference
A Michael Lincoff, Kirstine Brown-Frandsen, Helen M Colhoun et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232.
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