Obesity is a chronic disorder resulting from a prolonged energy imbalance, with a significant contribution of genetic, metabolic, and lifestyle factors, and is recognized as one of the leading global public health challenges. It is associated with the development of numerous chronic non-communicable diseases, including type 2 diabetes mellitus and cardiovascular diseases. Chronic low-grade inflammation represents a key pathophysiological link between obesity and its comorbidities, and SGLT2 inhibitors have been shown to exert anti-inflammatory effects, providing a biological rationale for investigating their therapeutic potential in obesity management. SGLT2 inhibitors reduce glycemia via an insulin-independent mechanism and contribute to body weight loss through increased glucosuria. Although their beneficial metabolic effects are well documented in patients with T2DM, evidence regarding their efficacy in reducing body weight in patients without T2DM remains limited, and their therapeutic positioning relative to GLP-1 receptor agonists has not been comprehensively evaluated. This systematized narrative review aims to address this gap by synthesizing available preclinical and clinical evidence on the effects of SGLT2 inhibitors on body weight and metabolic parameters in obese patients with and without T2DM. Preclinical studies demonstrate reductions in visceral adipose tissue, increased fatty acid oxidation, and activation of the browning of white adipose tissue. Clinical trials confirm modest but consistent reductions in body weight, generally ranging from 2 to 4 kg, in obese patients with and without T2DM, along with improvements in glycemic control and metabolic parameters. The long-term effectiveness of SGLT2 inhibitors in body weight management is limited by compensatory hyperphagia and plateau effects. Current evidence is insufficient to support their routine use as primary anti-obesity agents. Compared to GLP-1 receptor agonists and dual incretin therapies, the magnitude of weight loss achieved with SGLT2 inhibitors remains substantially lower. Therefore, SGLT2 inhibitors are best positioned as adjunctive components of a comprehensive metabolic therapeutic strategy.
Baletic et al. (Wed,) studied this question.