Diabetes Dialogue: SCORE, Semaglutide, and ACC Wrap-up

Welcome back to Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives!

In this episode, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, break down a pair of studies examining the effects of semaglutide and long-acting GLP-1 receptor agonists (GLP-1 RAs).

Real-World Semaglutide Effects from SCORE Study

Building on the SELECT trial, which demonstrated semaglutide 2.4 mg (Wegovy) significantly reduced cardiovascular risk in people with atherosclerotic cardiovascular disease (ASCVD) and obesity but without diabetes, the new SCORE study provides real-world validation of these benefits in a US population.

Using claims and EMR data, researchers matched 9321 semaglutide 2.4 mg users with 18,642 non-users, all aged 45 years or older, with ASCVD and overweight or obesity but no diabetes. The groups were balanced using a propensity score matching method.

The analysis showed that semaglutide 2.4 mg use was associated with a 46% lower risk of 5-point major adverse cardiovascular events (MACE)—which includes myocardial infarction, stroke, hospitalization for heart failure, coronary revascularization, and all-cause death (HR, 0.54; 95% CI, 0.43 to 0.69; P <.001). The risk of all-cause death alone was reduced by 87% in semaglutide users compared to non-users (HR, 0.13; 95% CI, 0.06 to 0.28; P <.001).

Meta-analysis of Randomized Trials for GLP-1s in T2D

A new meta-analysis, including recently published data from the SOUL and FLOW trials, reinforces the cardiovascular and kidney benefits of long-acting GLP-1 Res in individuals with type 2 diabetes.

Across 10 large, placebo-controlled trials containing 71,351 individuals, long-acting GLP-1RAs were associated with a 14% reduction in MACE (HR, 0.86; 95% CI, 0.81 to 0.90; I² = 27.6%), a 14% reduction in hospitalization for heart failure (HR, 0.86; 95% CI, 0.79 to 0.93; I² = 2.1%), and a 17% reduction in a composite kidney outcome (HR, 0.83; 95% CI, 0.75 to 0.92; I² = 20.4%). All-cause mortality was reduced by 12% (HR, 0.88; 95% CI, 0.82 to 0.93; I² = 17.5%), and each individual MACE component—cardiovascular death, myocardial infarction, and stroke—showed a consistent 14% risk reduction.

Benefits were consistent regardless of administration route, and no increased risks were observed for severe hypoglycemia, retinopathy, or pancreatic events.

Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

1. Zhao Z, Song J, Faurby M, et al. LOWER RISK OF MACE AND ALL-CAUSE DEATH IN PATIENTS INITIATED ON SEMAGLUTIDE 2.4 MG IN ROUTINE CLINICAL CARE: RESULTS FROM THE SCORE STUDY (SEMAGLUTIDE EFFECTS ON CARDIOVASCULAR OUTCOMES IN PEOPLE WITH OVERWEIGHT OR OBESITY IN THE REAL WORLD). Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

2. Lee MMY, Sattar N, Pop-Busui R, et al. Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials. Diabetes Care. Published online March 29, 2025. doi: 10.2337/dc25-0241