MON-706 Metabolic Saviour or Muscle Menace : The Unresolved SGLT2 Inhibitor Paradox

Abstract Disclosure: S. Savithri nandeesha: None. M. Yabe: None. M. Ramakrishnan: None. N. Ikkurthy: None. V. Yadav: None. M. Shaikh: None. S. Bansal: None. S. Mallikarjun: None. S. Biradar: None. T. Ismail: None. Z. Shaheen: None. Sarcopenia is a progressive disease characterized by the loss of muscle mass, strength, and function. The bidirectional relationship between Heart Failure(HF) and muscle loss creates a vicious circle called the frailty circle. A similar relationship exists with type 2 Diabetes Mellitus (T2DM) and muscle loss primarily due to Insulin resistance. While sodium-glucose co-transporter 2 (SGLT2) inhibitors, a novel class of oral hypoglycemic agents, are gaining prominence for their renal and cardiovascular protective effects, as well as their ability to promote weight loss, the impact of these agents on body composition, specifically muscle mass, remains unclear. Previous studies have suggested that SGLT2 inhibitors may contribute to muscle atrophy, particularly in older patients and those with pre-existing muscle weakness. Clinicians have expressed growing concern over their potential association with lean muscle loss and the adverse effects of frailty and sarcopenia. However, our systematic review of the latest studies presents a different perspective. Our analysis suggests that SGLT2 inhibitors, beyond their well-established cardiovascular benefits even among elderly diabetics and frail patients, also maintain a favorable safety profile and may contribute to a slight reduction in frailty-related complications. This conflicting evidence creates significant clinical uncertainty, hindering optimal treatment strategies for elderly patients at risk of sarcopenia. It also underscores the need for further research into the long-term effects of SGLT2 inhibitors on muscle health. We emphasize the necessity of large, long-term trials that examine the molecular mechanisms underlying the effects of SGLT2 inhibitors on skeletal muscle. Such studies should also assess their risk-benefit profile across diverse populations, considering variations in lean mass across age, sex, race, and ethnicity. Furthermore, future research should investigate the role of lifestyle interventions, such as exercise and nutrition, in mitigating potential muscle loss associated with SGLT2 inhibitors. To enhance clinical decision-making, comprehensive assessments of muscle mass and function, including dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and hand grip strength, should be incorporated into routine monitoring of patients on SGLT2 inhibitors. This will provide a more nuanced understanding of their impact on muscle function, guiding tailored treatment approaches and improving outcomes in patients with sarcopenia. Presentation: Monday, July 14, 2025