SGLT2 Inhibitor Reduces Visceral Adiposity in T2DM

November 25, 2014

The mechanism underlying the ability of empagliflozin to reduce measures of visceral adiposity may be a redistribution of fat to less vulnerable body areas.

The sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin significantly reduced weight and markers of visceral adiposity in patients with type 2 diabetes compared with placebo, according to results of a study presented at the American Heart Association Scientific Sessions 2014.

“Our research contributes further evidence demonstrating important off-target effects of SGLT2 inhibitors, including beneficial effects on blood pressure and body composition,” study author Ian J. Neeland, MD, of the University of Texas Southwestern Medical Center, told Endocrinology Network. “Further research is needed to drill deeper into the potential mechanisms for these findings and how we can use them to treat patients with type 2 diabetes in the future.”

According to Neeland, visceral adiposity is emerging as a major risk factor for the development of cardiometabolic disease, including type 2 diabetes mellitus (T2DM). However, few therapies positively affect both hyperglycemia and dysfunctional adiposity in patients with diabetes because many therapies for diabetes cause weight gain.

In prior phase III trials, empagliflozin had been found to improve glycemic control and reduce weight in T2DM patients. In this study, Neeland and colleagues wanted to explore if empagliflozin had any effect on markers of visceral adiposity.

The researchers explored these outcomes using two cohorts. Cohort 1 included patients with T2DM and hypertension who participated in a 12-week phase III trial and were randomly assigned to placebo (n=271) or empagliflozin (n=552). Cohort 2 patients had T2DM and had participated in one of four 23-week phase III trials and were randomly assigned to placebo (n=825) or empagliflozin (n=1,652).

In cohort 1, patients assigned to the study drug had a mean reduction in weight of 1.9 kg compared with a reduction of 0.2 kg for placebo (P<.001). In cohort 2, patients assigned the study drug had a mean body weight reduction of 2.2 kg compared with a mean 0.2-kg reduction for patients receiving placebo (P <.001).

Looking at markers of visceral adiposity, patients assigned empagliflozin also had significant reductions from baseline compared with placebo for:

  - Waist circumference (cohort 1: -1.3 cm vs -0.2 cm; cohort 2: -1.5 cm vs -0.2 cm; P <.001 for both)
  - Index of central obesity (cohort 1 & 2: -0.009 vs -0.001; P<.001 for both)
  - Visceral adiposity index (cohort 2: -0.2 vs. 0.2; P=.003).

“These results suggest that treatment with empagliflozin may lead to changes in body composition associated with improved cardiovascular disease risk,” Neeland said.

Neeland noted that these results were not surprising given the improvements seen with empagliflozin in visceral adiposity measured by MRI.  However, he added that one of the most interesting findings in this study was that estimated total body fat was not significantly different between empagliflozin- and placebo-treated patients. 

“Therefore, empagliflozin decreased markers of visceral adiposity out of proportion to overall changes in body fat, suggesting that, even without significant loss of body fat, empagliflozin may help to redistribute fat to areas in the body with a better cardiometabolic risk profile and away from the visceral depot,” Neeland said.  

“If our results are confirmed, empagliflozin may emerge as a strategy to treat the dysfunctional adiposity related to diabetes in addition to its effects on glycemia.”

References:

Neeland IJ. #16518. The sodium glucose cotransporter 2 inhibitor empagliflozin reduces weight and markers of visceral adiposity in type 2 diabetes in short and intermediate term. Presented at: American Heart Association Scientific Sessions 2014; Nov. 16-19, 2014; Chicago.