Oral administration of a fixed-dose combination of the SGLT2 inhibitor dapagliflozin (DAPA) and the DPP-4 inhibitor saxagliptin (SAXA) is approved for improving glycemic control in adult patients with type 2 diabetes (T2D). A 52-week, multicenter, randomized, double-blind, parallel-group trial (NCT02419612) evaluated the efficacy and safety of DAPA 10 mg/d + SAXA 5 mg/d vs. titrated glimepiride (GLIM) 1-6 mg/d in 443 patients with T2D (A1C 7.5-10.5%) on metformin (MET) ≥1500 mg/d background. In a substudy, we used magnetic resonance imaging (MRI) to assess effects on liver fat (proton density fat fraction [PDFF]) and visceral and subcutaneous adipose tissue volumes over 52 weeks of treatment. MRI was performed on 59 patients; liver fat and adipose tissue volumes were analyzed for 59 and 57 patients, respectively. There was a significant >30% reduction from baseline in liver fat (P=0.007) and a >10% reduction in adipose tissue volumes (P<0.01) with DAPA + SAXA + MET at week 52 vs. GLIM + MET (Table). In the full study population, DAPA + SAXA + MET decreased body weight and serum levels of alanine aminotransferase and aspartate aminotransferase over 52 weeks.
In conclusion, DAPA + SAXA significantly decreased liver fat and adipose tissue volume vs. GLIM, and reduced serum liver enzyme levels, indicating a favorable metabolic profile of DAPA + SAXA in patients with T2D on MET therapy.
J.P. Wilding: Other Relationship; Self; Astellas, AstraZeneca, Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Eli Lilly and Company, Orexigen Therapeutics, Inc., Merck & Co., Inc. P. Hockings: Other Relationship; Self; MedImmune, AstraZeneca. E.K. Johnsson: Employee; Self; AstraZeneca. J. Maaske: Employee; Self; AstraZeneca. Employee; Spouse/Partner; AstraZeneca. Stock/Shareholder; Spouse/Partner; AstraZeneca. R. Garcia-Sanchez: Employee; Self; AstraZeneca. L. Johansson: Stock/Shareholder; Self; Antaros Medical.