SGLT2 Inhibitors vs Metformin: Cardiovascular Protection in Type 2 Diabetes Patients

Irakoze Mukamana S.

School of Applied Health Sciences Kampala International University Uganda

                                                                         ABSTRACT
Type 2 diabetes mellitus affects over 537 million adults globally and represents the leading cause of cardiovascular morbidity and mortality, with diabetic patients experiencing a 2- to 4-fold increased risk of major adverse cardiovascular events compared to non-diabetic populations. This narrative review compared the cardiovascular protective mechanisms and clinical efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors versus metformin in type 2 diabetes management. A comprehensive literature search was conducted across PubMed, Embase, and Web of Science databases from 2008 to 2024, focusing on cardiovascular outcome trials, mechanistic studies, and comparative effectiveness research. SGLT2 inhibitors demonstrated superior cardiovascular protection through multiple mechanisms, including osmotic diuresis, cardiac energy metabolism optimization, and direct myocardial protective effects, with major trials showing a 13-17% reduction in cardiovascular death compared to placebo. Metformin provided cardiovascular benefits primarily through AMP-activated protein kinase activation and improved insulin sensitivity, though evidence derives predominantly from observational studies rather than dedicated cardiovascular outcome trials. Head-to-head comparisons revealed that SGLT2 inhibitors confer greater cardiovascular risk reduction, particularly for heart failure hospitalization (35-39% reduction) and cardiovascular mortality, while metformin demonstrates superior glycemic control and metabolic benefits. Both drug classes exhibited complementary mechanisms that support combination therapy approaches. The evidence strongly supported SGLT2 inhibitors as first-line therapy for diabetic patients with established cardiovascular disease or high cardiovascular risk, while metformin remains optimal for metabolic control in lower-risk populations.

Keywords: SGLT2 inhibitors, Metformin, Cardiovascular protection, Type 2 diabetes, Heart failure.

CITE AS: Irakoze Mukamana S. (2026). SGLT2 Inhibitors vs Metformin: Cardiovascular Protection in Type 2 Diabetes Patients. Research Output Journal of Public Health and Medicine 6(1):100-106.
https://doi.org/10.59298/ROJPHM/2026/61100106