What are the findings of the SCORE study on semaglutide (glucagon-like peptide-1 receptor agonist) for cardiovascular risk reduction in type 2 diabetes?

Summary of the SCORED Study

The SCORED study evaluated sotagliflozin (an SGLT1/SGLT2 inhibitor), not semaglutide—there appears to be confusion in the question, as SCORED does not involve semaglutide. 1

SCORED Trial Overview

• SCORED stands for "Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk" 1

• The trial enrolled 10,584 patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk factors 1

• Patients were randomized to sotagliflozin 200 mg once daily (uptitrated to 400 mg once daily if tolerated) or placebo 1

Key Methodological Issues

• The trial ended prematurely due to lack of funding, which significantly impacted the study design and interpretation 1

• Changes to the prespecified primary endpoints were made prior to unblinding to accommodate a lower than anticipated number of endpoint events 1

• The primary endpoint was modified to the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure 1

Important Distinction: Semaglutide Studies

If you are asking about semaglutide cardiovascular outcomes, the relevant trials are:

SUSTAIN-6 (Subcutaneous Semaglutide)

• Semaglutide demonstrated cardiovascular benefit with a 26% reduction in major adverse cardiovascular events (MACE) compared to placebo 1, 2, 3

• 3,297 patients with type 2 diabetes were randomized to once-weekly subcutaneous semaglutide (0.5 mg or 1.0 mg) or placebo for 2 years 1, 3

• The primary outcome (cardiovascular death, nonfatal MI, or nonfatal stroke) occurred in 6.6% of the semaglutide group versus 8.9% in the placebo group (HR 0.74 [95% CI 0.58–0.95]; P < 0.001) 1, 3

• More patients discontinued semaglutide due to adverse events, mainly gastrointestinal 1, 3

• Rates of retinopathy complications were significantly higher with semaglutide (HR 1.76; 95% CI 1.11 to 2.78; P=0.02), including vitreous hemorrhage, blindness, or conditions requiring intravitreal treatment or photocoagulation 3

PIONEER-6 (Oral Semaglutide)

• 3,183 patients with type 2 diabetes and high cardiovascular risk were followed for a median of 15.9 months 1, 4

• Oral semaglutide was noninferior to placebo for the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.79 [95% CI 0.57–1.11]; P < 0.001 for noninferiority) 1, 4

• This was a pre-approval trial designed to rule out unacceptable cardiovascular risk, not to demonstrate superiority 1, 4

SOUL Trial (Oral Semaglutide - Most Recent)

• Among 9,650 participants with type 2 diabetes and atherosclerotic cardiovascular disease or chronic kidney disease, oral semaglutide reduced MACE by 14% over a median follow-up of 49.5 months 5

• Primary outcome events occurred in 12.0% of the oral semaglutide group versus 13.8% in the placebo group (HR 0.86; 95% CI 0.77 to 0.96; P = 0.006) 5

• The incidence of serious adverse events was 47.9% in the oral semaglutide group versus 50.3% in the placebo group 5

Clinical Bottom Line

If you meant to ask about semaglutide cardiovascular outcomes: Semaglutide is FDA-approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, based primarily on SUSTAIN-6 data showing a 26% MACE reduction 2, 6, 3. The American College of Cardiology recommends semaglutide for patients with established cardiovascular disease and type 2 diabetes 2.