(53) Cardiovascular Outcomes of GLP-1 Receptor Agonists Versus Metformin as First-Line Treatment for Type 2 Diabetes

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 727

Presenting Author(s)

HoJin Shin
– Harvard School of Public Health, Boston, Massachusetts, United States

Co-Author(s)

Sebastian Schneeweiss, ScD, MD, FISPE
– Professor of Medicine, BWH Div of Pharmacoepidemiology and Pharmacoeconomics, Boston, Massachusetts, United States
Robert Glynn, PhD, ScD
– Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States
Elisabetta Patorno
– Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, United States

Background: Cardiovascular (CV) benefits of glucagon-like peptide 1 receptor agonists (GLP-1RA) shown from cardiovascular outcome trials have raised the question whether GLP-1RA should be advanced to first-line treatment for patients with type 2 diabetes (T2D) and CV disease (CVD). However, evidence on CV benefits associated with the use of GLP-1RA is limited when compared with the recommended first-line metformin.

Objectives: We investigated CV outcomes of first-line GLP-1RA versus metformin among adults with T2D.

Methods: Data from two U.S. commercial health insurance and Medicare fee-for-service claims was used. We identified T2D patients aged 18 years (>65 in Medicare) who initiated first-line GLP-1RA with established CV benefits (dulaglutide, liraglutide, and semaglutide) or metformin between 4/2013–6/2021, without using any antidiabetic drugs before cohort entry. Propensity score (PS) matching (1:2 ratio) was used to achieve a balance between GLP-1RA and metformin initiators. The primary outcome was a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality. The secondary outcomes were the component endpoints and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. We also conducted subgroup analyses by baseline CVD.

Results: GLP-1RA initiators (n=13,088) were younger, more likely female and obese, and had a higher burden of diabetic complications, a similar burden of CVD, more frequent office visits or HbA1c test orders, and fewer recent hospitalizations compared with metformin initiators (n=905,686). After PS-matching of 12,269 GLP-1RA to 24,538 metformin initiators across the three databases, patient characteristics were well balanced. Compared with metformin, GLP-1RA showed a similar risk of the primary outcome (HR=0.83, 95% CI: 0.67–1.03) during a mean follow-up of 10.5 months. GLP-1RA and metformin also showed similar risk for MI (0.91, 0.65–1.27), stroke (0.97, 0.65–1.44), all-cause mortality (0.73, 0.51–1.03), and HHF (1.08, 0.90–1.28). Results were consistent across levels of baseline CVD.

Conclusions: Compared with metformin, first-line GLP-1RA use was associated with a trend toward a lower risk of a composite of MI, stroke, or all-cause mortality.