SGLT2 Inhibitors Can Aid Weight Loss, Reduce Fat Mass in People with Type 2 Diabetes

A systematic review and meta-analysis is providing insight into the effects of SGLT2 inhibitor use on body composition in people with type 2 diabetes.

Results of the study, which included data from more than a dozen studies, detail the positive effects of SGLT2 inhibitor use on body weight, BMI, waist circumference, and fat mass, but also shed light on the potential negative impact on lean mass.

“The highlight of this meta-analysis is to confirm not only the advantages of SGLT2 inhibitors in improving body composition, such as weight loss, BMI, waist circumference, visceral fat area, subcutaneous fat area, percentage body fat, and fat mass reduction, but also the adverse effects of these drugs on muscle mass reduction,” wrote investigators.

In recent years, few, if any, therapeutic areas in cardiometabolic health have seen a revolution in use as hypoglycemic agents. As SGLT2 inhibitors have stolen headlines for their cardiorenal protective benefits, GLP-1 receptor agonists have seen their role expand into weight management outside of diabetes. Although reported in trials, many questions remain surrounding the potential magnitude of weight loss and effects on composition of SGLT2 inhibitor use.

Citing this, and an interest in exploring a potential association with increased risk of sarcopenia, a team from the Cangzhou Central Hospital designed the present systematic review and meta-analysis of randomized clinical trials examining SGLT2 inhibitor use in people with type 2 diabetes. Performing a search of the PubMed, Cochrane Library, Embase, and Web of Science databases for randomized clinical trials examining SGLT2 inhibitor use published from 2013-2022, investigators identified 18 studies with a total of 1430 participants for inclusion. Among the studies, 3 examined canagliflozin, 8 examined dapagliflozin, 3 examined empagliflozin, and 4 examined ipragliflozin.

Outcomes of interest for the investigators’ analyses included changes in body weight, BMI, waist circumference, percentage body fat, fat mass, muscle mass, visceral fat area, subcutaneous fat area, lean mass, and skeletal muscle mass. Investigators pointed out results were compared by weight mean difference (WMD).

In 14 randomized clinical trials reporting body weight, results indicated use of SGLT2 inhibitors was associated with significantly decreased body weight relative to the trials’ comparator agents (WMD, -2.73 kg [95% CI , -3.32 to -2.13]; P <.00001), with investigators reporting low heterogeneity between studies (I2=33%), In 7 trials reporting BMI, use of SGLT2 inhibitors was associated with significantly decreased BMI relative to the trials’ comparator agents.

Further analysis revealed use of ASGLT2 inhibitors was associated with reductions in ways circumference (WMD, -2.20 cm [95% CI, -3.81 to -0.58]; P=.008), visceral fat area (WMD, -14.79 cm2 [95%CI, -24.65 to -4.93] P=.003), subcutaneous fat area (WMD, -23.27 cm2, 95% CI:-46. 44 to -0.11]; P=.05), fat mass (WMD, -1.16 kg [95%CI, -2.01 to -0.31]; P= .008), percentage body fat (WMD, -1.50% [95% CI, -2.12 to -0.87]; P <.00001). Investigators also pointed out use of SGLT2 inhibitors was associated with statistically significant decreases in lean mass (WMD, -0.76 kg [95% CI, -1.53 to 0.01]; P=.05) and skeletal muscle mass (WMD, -1.01 kg [95% CI, -1.91 to -0.11]; P=.03).

“Until more evidence is obtained to support that SGLT-2 inhibitors increase the risk of sarcopenia, not only the benefit on body composition, but also the adverse effects of the reduction on muscle mass by SGLT-2 inhibitors in T2DM should be considered,” concluded investigators.

This study, “Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials,“ was published in PLOS ONE.