Plasma B-Type Natriuretic Peptide Levels May Increase Because of Fat Mass Loss by Metformin or Sodium-Glucose Transporter 2 Inhibitors Treatment

Abstract

Background: Cardiovascular disease (CVD) is the leading cause of death in type 2 diabetes. Metformin reduces cardiovascular events in obese patients with type 2 diabetes, and sodium-glucose transporter 2 (SGLT2) inhibitors decrease cardiovascular events in type 2 diabetic patients with established CVD. However, the underlying mechanisms behind the cardioprotective effects of metformin and SGLT2 inhibitors are unknown. Methods: Fifteen patients with newly diagnosed type 2 diabetes receiving metformin monotherapy, and seven patients with type 2 diabetes receiving SGLT2 inhibitors combined with other hypoglycemic agents were studied. We investigated changes in glycemic control, plasma B-type natriuretic peptide (BNP) levels, and body composition, 3 and 6 months after starting metformin administration, and 3 months after starting SGLT2 inhibitor administration. Results: Plasma BNP levels significantly increased after 3 months in both metformin and SGLT2 inhibitors treatment groups (7.9 ± 7.9 pg/mL to 17 ± 16.9 pg/mL, P = 0.012; 8.8 ± 7.2 pg/mL to 15.5 ± 14.3 pg/mL, P = 0.018, respectively). Fat mass significantly decreased in the first 3 months of metformin administration (25.7 ± 10.3 kg to 23.0 ± 11.4 kg, P = 0.046), while fat mass and visceral fat area decreased in three patients receiving SGLT2 inhibitors. Conclusions: Plasma BNP levels increased because of fat mass loss caused by treatment with metformin and SGLT2 inhibitors. Our results suggest that metformin and SGLT2 inhibitors could reduce the risk of CVD by exerting cardioprotective effects through elevated BNP levels in patients with type 2 diabetes. J Endocrinol Metab. 2016;6(1):12-17 doi: http://dx.doi.org/10.14740/jem333w