Comparing the Effects of Ipragliflozin and Metformin on Visceral Fat Reduction in Patients with Type 2 Diabetes Inadequately Controlled with Sitagliptin–A Prospective, Multicenter, Blinded-Endpoint, Randomized Controlled Study in Japan (PRIME-V Study)

Abstract

Objective: To determine the effects of SGLT2 inhibitor or metformin on reducing visceral fat in Asian patients with type 2 diabetes inadequately controlled with DPP-4 inhibitor, sitagliptin. Methods: A prospective, multicenter, blinded-endpoint, randomized controlled trial was conducted to evaluate the efficacy of treatment with either SGLT2 inhibitor (ipragliflozin) or metformin added on to sitagliptin for visceral fat reduction and glucose control in patients with type 2 diabetes. Patients who met the eligibility criteria were randomly selected (1:1) to receive ipragliflozin (Ipr; 50 mg daily) or metformin (Met; 1000 mg daily). The primary outcome is the change rate in visceral fat area, measured using computed tomography, after 24 weeks of therapy. Two radiologists, blinded to the information, analyzed the images. Results: A total of 51 patients were in enrolled in the Ipr group and 52 in the Met group. The reduction rate in visceral fat area was significantly greater in the Ipr group (-12.06% vs. -3.65%, group difference of -8.40%; 95% CI of -16.4 to -3.38, P<0.05) than in the Met group. Subcutaneous fat area, total fat area, body weight, BMI, and waist circumference also decreased significantly in the Ipr group. The Ipr group showed a significant decrease in fasting insulin (-20.73% vs. 0.85%, group difference -21.58%, 95% CI 2.80 to 34.20, P<0.05), while HbA1c decreased in the Met group compared with the Ipr group. The difference in the muscle volume and bone mineral density between the two groups was insignificant. Conclusion: Ipr significantly reduced the visceral fat area compared with Met as the secondary agent used in combination with DPP-4 inhibitors. As the fasting insulin level decreased, the reduction in visceral fat associated with Ipr administration may have contributed to the improvement of insulin resistance. Disclosure M. Koshizaka: None. K. Ishikawa: None. R. Ishibashi: None. Y. Maezawa: None. K. Sakamoto: None. D. Uchida: Speaker's Bureau; Self; Takeda Pharmaceuticals Japan, Tanabe Mitsubishi Pharmaceuticals Japan, Sanofi, MSD K.K., Novo Nordisk Inc. S. Nakamura: None. H. Yokoh: None. A. Kobayashi: None. S. Onishi: None. K. Kobayashi: None. J. Ogino: None. H. Tokuyama: None. F. Shimada: None. E. Ohara: None. T. Ishikawa: None. M. Shoji: None. K. Ide: None. S. Ide: None. Y. Baba: None. T. Horikoshi: None. R. Shimofusa: None. S. Takahashi: None. K. Nagashima: None. M. Takemoto: None. K. Yokote: Research Support; Self; Astellas Pharm Ltd, MSD K.K..