SCORE Study with Semaglutide: Real-World Cardiovascular Outcomes
Critical Clarification: Two Different SCORE Studies
There are two distinct studies with "SCORE" in their names involving different medications—one evaluating sotagliflozin (SCORED trial) and one evaluating semaglutide 2.4 mg (SCORE study). The semaglutide SCORE study is the real-world observational study examining cardiovascular outcomes in patients with overweight/obesity and established cardiovascular disease but without diabetes 1.
SCORE Study Design and Population
The SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World) was a real-world observational study conducted using US database records from 2016-2023 1.
Key enrollment criteria included:
- Individuals aged ≥45 years with established atherosclerotic cardiovascular disease (ASCVD) 1
- Overweight or obesity present 1
- Critically, patients did NOT have diabetes—this distinguishes it from SUSTAIN-6 and other diabetes trials 1
- Patients initiated on semaglutide 2.4 mg (the weight management dose, not the diabetes dose) 1
The study matched 9,321 individuals on semaglutide 2.4 mg to 18,642 individuals not on semaglutide using propensity-score matching to balance patient characteristics 1.
Primary Cardiovascular Outcomes: Dramatic Risk Reductions
Semaglutide 2.4 mg demonstrated remarkably strong cardiovascular benefits over a mean follow-up of 200 days (approximately 6.5 months):
Revised MACE Outcomes
- Revised 5-point MACE (rMACE-5): 45% risk reduction (HR 0.55, p < 0.001) 1
- Components: MI, stroke, all-cause mortality, coronary revascularization, and hospitalization for heart failure
- Revised 3-point MACE (rMACE-3): 57% risk reduction (HR 0.43, p < 0.001) 1
- Components: MI, stroke, and all-cause mortality
Traditional MACE Outcomes
- MACE-5: 35% risk reduction (HR 0.65, p < 0.001) 1
- Same as rMACE-5 but using cardiovascular-related mortality instead of all-cause mortality
- MACE-3: 42% risk reduction (HR 0.58, p < 0.01) 1
- Same as rMACE-3 but using cardiovascular-related mortality instead of all-cause mortality
Individual Component Outcomes
Semaglutide 2.4 mg significantly reduced:
Exploratory Outcomes: Beyond Cardiovascular Disease
Additional benefits observed included:
- Lower risk of incident type 2 diabetes 1
- Reduced major adverse kidney events 1
- Decreased major obesity-related adverse events 1
Clinical Context: How SCORE Differs from SUSTAIN-6
While SUSTAIN-6 demonstrated a 26% reduction in MACE (HR 0.74) in patients with type 2 diabetes over 2 years 2, 3, the SCORE study showed even more pronounced benefits in a non-diabetic population with obesity and established cardiovascular disease over a much shorter timeframe 1. This suggests semaglutide's cardiovascular benefits extend beyond glycemic control and may be mediated through weight reduction, blood pressure lowering, and direct vascular effects 3.
Important Caveats and Limitations
This was an observational real-world study, not a randomized controlled trial, which introduces potential for residual confounding despite propensity-score matching 1. The relatively short mean follow-up of 200 days limits assessment of long-term outcomes 1. The dramatic effect sizes (43-57% risk reductions) are substantially larger than those seen in randomized trials like SUSTAIN-6, which may reflect selection bias, healthy user effects, or differences in the study populations 1, 2.
Common adverse events with semaglutide are primarily gastrointestinal, including nausea and vomiting 2, 3. Gradual dose titration starting at 0.25 mg weekly helps minimize these effects 3.