Review synthesizing clinical evidence on SGLT2 inhibitors, GLP-1 RAs, and dual GIP/GLP-1 agonists (tirzepatide) for 'diabesity' (concurrent obesity and T2DM), covering BMI reduction, body composition changes, and glucose metabolism improvements. Compares the mechanisms and outcomes across these three drug classes. Provides an integrated pharmacotherapy framework for diabesity management—identifying how tirzepatide's dual agonism achieves superior weight and glycemic outcomes versus either drug class alone, supporting its emerging role as the preferred pharmacotherapy for patients with both conditions.
Abstract
PURPOSE OF REVIEW: This review aims to provide a comprehensive synthesis of current clinical evidence on the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonists on body mass index (BMI), body composition, and glucose metabolism in patients with obesity and type 2 diabetes mellitus (T2DM), a condition often referred to as "diabesity."
RECENT FINDINGS: The coexistence of obesity and T2DM represents a major clinical and public health challenge due to their synergistic effects on metabolic dysfunction and the increased risk of cardiovascular and renal complications. Traditional approaches focused solely on glycemic control have proven insufficient to address the intertwined pathophysiology of excess adiposity and impaired glucose metabolism. Recently, novel pharmacological agents, including SGLT2 inhibitors, GLP-1 RAs, and dual GIP/GLP-1 receptor agonists, have demonstrated dual benefits in improving glycemic control and reducing body weight. These drugs act through distinct but complementary mechanisms-such as promoting glycosuria, enhancing satiety, delaying gastric emptying, and modulating energy homeostasis-resulting in significant reductions in BMI and visceral fat. Among these agents, tirzepatide has shown superior efficacy in improving metabolic parameters and body composition compared with single receptor agonists. Understanding the multifaceted metabolic benefits of these pharmacotherapies is essential for optimizing individualized therapeutic strategies for patients with diabesity. Integrating these agents into comprehensive diabetes care allows clinicians to more effectively target the complex pathophysiology of diabesity, ultimately improving long-term metabolic and clinical outcomes in this growing patient population.