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.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.