Can an SGLT2 Inhibitor Improve Adipose Tissue Function in Type 2 Diabetes?

Patients with type 2 diabetes who take canagliflozin have better adipose tissue function than those who take glimepiride, according to an abstract presented at the American Association of Clinical Endocrinologists Annual Meeting. The improvement in function was independent of weight loss, researchers said.

In a previously conducted 52-week, phase 3 trial, canagliflozin was more successful at reducing HbA1c and at reducing overall body weight through loss of fat mass, compared with glimepiride. Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor.

The current study, a post-hoc analysis of the original trial, examined the impact of canagliflozin compared with glimepiride on certain adipokines (serum leptin, adiponectin and leptin-to-adiponectin ratio), inflammatory markers [C-reactive protein, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)], and chemokines [plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1)] that have been associated with impaired adipose tissue function, insulin resistance, and cardiovascular disease.

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The researchers examined serum samples from 100 randomly selected patients who received 300 mg of canagliflozen daily and 100 randomly selected patients who received glimepiride without rescue therapy.

When patients were assessed at week 52, the least squares mean (LSM) change in HbA1c was –0.99% with canagliflozen and –0.91% with glimepiride. With canagliflozen, the LSM change in body weight was –4.1 kg, while the LSM change was 0.7 kg with glimepiride.

Compared with patients taking glimepiride, those taking canagliflozen had a 26% decrease in serum leptin at week 52 and a 17% increase in serum adiponectin. In addition, patients in the canagliflozin group had a 23% reduction in serum IL-6 and a 9% increase in median serum TNF-α versus those in the glimepiride group.

No differences between groups were seen with CRP, PAI- 1, VCAM-1, or MCP-1. The researchers noted that change in leptin was linked with change in body weight (r ≥0.35) only, but change in adiponectin and IL-6 were not associated with change in body weight, lipids, or HbA1c.

“The CANA-related changes in leptin, adiponectin, and IL-6 were independent of glycemic benefit, and the changes in adiponectin and IL-6 were independent of weight loss in this analysis. These collective results suggest that CANA may improve adipose tissue function, which may have positive effects on cardiometabolic health,” the researchers concluded.

—Lauren LeBano

Reference

Garvey T, Gaal LV, Lieter L, et al. Effects of canagliflozin versus glimepiride on adipokines, inflammatory biomarkers, and chemokines in patients with type 2 diabetes mellitus. Abstract 252.