SGLT2 Inhibitors and the Clinical Implications of Associated Weight Loss in Type 2 Diabetes: A Narrative Review

INTRODUCTION: The obesity epidemic is closely linked to the rising prevalence of type 2 diabetes (T2D). Body weight reduction remains an important challenge in patients with T2D, as it requires changing their overall metabolic control. Of all glucose-lowering therapies, only sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) consistently result in weight improvement. Moreover, the same two classes have important cardiovascular and renal benefits. We summarize the key available information related to the weight loss effect of SGLT2is in T2D, focusing on the unexploited potential of these drugs. METHODS: Data on weight change with SGLT2is in patients with T2D were extracted from published cardiovascular outcomes trials (CVOTs). A discussion on patient perspectives about weight change is based on key preclinical and clinical trials, meta-analyses, and reviews and is supplemented by the authors’ clinical judgment and research experience in the field. RESULTS: SGLT2is have a unique mode of action resulting in caloric loss through glycosuria. The anticipated weight loss with SGLT2is is not reflected in clinical trial results. There is a discrepancy between the magnitude of improvement in glycemic control and the weight loss, cardiovascular, and renal benefits obtained in large clinical trials. CONCLUSION: The relationships between the magnitude of weight loss, improvement in glycemic control, and cardiorenal benefits with SGLT2i are still unclear. Potential mechanisms other than simple glycemic efficacy should be revealed and explained. Better weight control may be achieved if adequately intensive lifestyle changes are implemented and monitored in the T2D population treated with SGLT2is.