GLP-1 Receptor Agonist and SGLT2 Inhibitor Combination Therapy in Type 2 Diabetes Management
Mercy Latricia
Department of Pharmacognosy Kampala International University Uganda
Email: atricia.mercy@studwc.kiu.ac.ug
ABSTRACT
Type 2 diabetes mellitus (T2DM) affects approximately 537 million adults globally, with projections indicating 783 million cases by 2045, driving substantial cardiovascular and renal morbidity. Monotherapy with glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2i) provided glycemic control alongside organ-protective benefits, yet many patients fail to achieve composite metabolic targets. This narrative review critically evaluated the biochemical rationale, clinical evidence, and safety profile of combining GLP-1RAs with SGLT2i in T2DM management. A comprehensive literature search was conducted in PubMed, Embase, and Web of Science databases covering January 2017 through March 2025, focusing on randomized controlled trials, meta-analyses, and mechanistic studies. Current evidence demonstrated that combination therapy produces complementary mechanisms through incretin-mediated insulin secretion enhancement and renal glucose excretion, achieving superior HbA1c reductions (mean additional 0.6–1.2% beyond monotherapy), greater weight loss (3–5 kg additional reduction), and enhanced cardiovascular and renal protection with hazard ratios of 0.78–0.88 for major adverse cardiovascular events compared to either agent alone. Safety profiles showed acceptable tolerability with predominantly gastrointestinal and genitourinary adverse events that diminished over time, though cost considerations and long-term real-world effectiveness require further investigation. Combination GLP-1RA and SGLT2i therapy represented an evidence-based strategy for comprehensive T2DM management, offering synergistic metabolic and cardio-renal benefits that align with contemporary treatment paradigms emphasizing organ protection beyond glycemic control.
Keywords: GLP-1 receptor agonists; SGLT2 inhibitors; Type 2 diabetes; Combination therapy; Cardiovascular outcomes.
CITE AS: Muhindo Edgar (2026). GLP-1 Receptor Agonist and SGLT2 Inhibitor Combination Therapy in Type 2 Diabetes Management. IAA Journal of Biological Sciences 14(1):45-54.