COMPARATIVE EFFECTIVENESS OF SGLT2I, GLP-1, AND METFORMIN ON CARDIOVASCULAR OUTCOMES IN ADULTS WITH SEVERE MENTAL ILLNESS
Author(s)
Yueh-Yi Chiang, BSPharm1, Charmaine D. Rochester, PharmD1, Wendy Camelo Castillo, PhD1, Xiaojuan Li, PhD2, Chixiang Chen, PhD3, Susan Dosreis, PhD1;
1University of Maryland School of Pharmacy, Baltimore, MD, USA, 2Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA, 3University of Maryland School of Medicine, Baltimore, MD, USA
1University of Maryland School of Pharmacy, Baltimore, MD, USA, 2Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA, 3University of Maryland School of Medicine, Baltimore, MD, USA
OBJECTIVES: Individuals with severe mental illness (SMI) experience excessive cardiovascular (CV) mortality. CV benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1) in individuals with SMI are unknown. We assessed first-line treatment with SGLT2i/GLP-1 versus metformin on major adverse cardiovascular events (MACE) risk in individuals with SMI.
METHODS: Using a 20% random sample of US Medicare fee-for-service claims, we identified adults with SMI (schizophrenia, bipolar disorder, major depressive disorder) and type 2 diabetes (T2D) initiating SGLT2i, GLP-1, or metformin 1/1/2018-12/31/2021. Eligible individuals had continuous medical and pharmacy coverage and no oral antihyperglycemic prescriptions in the 12 months before treatment initiation. We excluded individuals with type 1/gestational diabetes, polycystic ovary syndrome, organ transplant, end-stage renal disease, or HIV/AIDS at baseline. Primary outcome was MACE (myocardial infarction, stroke, all-cause mortality); secondary outcomes were each MACE component and hospitalization for heart failure (HF). Follow-up began post-index until the earliest of the outcome, disenrollment, end of data (12/31/2022), or 3-year follow-up. We estimated intention-to-treat (ITT) and per-protocol (PP) effects of SGLT2i or GLP-1 versus metformin on cumulative risks of the outcomes using marginal structural models with inverse probability of censoring weights and Aalen-Johansen estimator for competing risk. Baseline confounders were balanced using overlap weighting.
RESULTS: Compared with metformin, SGLT2i ITT lowered 3-year MACE (risk ratio [RR]=0.90 [95% CI, 0.79-0.99]) and all-cause mortality (RR=0.84 [95%CI, 0.73-0.94]), but increased HF risk (RR=1.28 [95% CI, 1.06-1.44]). GLP-1 ITT lowered 3-year MACE (RR=0.81 [95% CI, 0.75-0.90]) and all-cause mortality (RR=0.77 [95% CI, 0.72-0.89]). The PP showed similar outcome effects as the ITT.
CONCLUSIONS: First-line SGLT2i and GLP-1 had a lower 3-year MACE risk versus metformin among adults with SMI and T2D, driven by all-cause mortality. We observed a higher HF risk with SGLT2i but not with GLP-1.
METHODS: Using a 20% random sample of US Medicare fee-for-service claims, we identified adults with SMI (schizophrenia, bipolar disorder, major depressive disorder) and type 2 diabetes (T2D) initiating SGLT2i, GLP-1, or metformin 1/1/2018-12/31/2021. Eligible individuals had continuous medical and pharmacy coverage and no oral antihyperglycemic prescriptions in the 12 months before treatment initiation. We excluded individuals with type 1/gestational diabetes, polycystic ovary syndrome, organ transplant, end-stage renal disease, or HIV/AIDS at baseline. Primary outcome was MACE (myocardial infarction, stroke, all-cause mortality); secondary outcomes were each MACE component and hospitalization for heart failure (HF). Follow-up began post-index until the earliest of the outcome, disenrollment, end of data (12/31/2022), or 3-year follow-up. We estimated intention-to-treat (ITT) and per-protocol (PP) effects of SGLT2i or GLP-1 versus metformin on cumulative risks of the outcomes using marginal structural models with inverse probability of censoring weights and Aalen-Johansen estimator for competing risk. Baseline confounders were balanced using overlap weighting.
RESULTS: Compared with metformin, SGLT2i ITT lowered 3-year MACE (risk ratio [RR]=0.90 [95% CI, 0.79-0.99]) and all-cause mortality (RR=0.84 [95%CI, 0.73-0.94]), but increased HF risk (RR=1.28 [95% CI, 1.06-1.44]). GLP-1 ITT lowered 3-year MACE (RR=0.81 [95% CI, 0.75-0.90]) and all-cause mortality (RR=0.77 [95% CI, 0.72-0.89]). The PP showed similar outcome effects as the ITT.
CONCLUSIONS: First-line SGLT2i and GLP-1 had a lower 3-year MACE risk versus metformin among adults with SMI and T2D, driven by all-cause mortality. We observed a higher HF risk with SGLT2i but not with GLP-1.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO133
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory), SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)