Objective: Evaluation of long-term results of combination therapy with dapagliflozin and metformin on fibrotic changes in the liver of patients with type 2 diabetes (DM) and nonalcoholic fatty liver disease (NAFLD).

Materials and Methods: We recruited 45 DM patients with clinical NAFLD (27M, 18F) and in addition to dietary recommendations all received dapagliflozin 10 mg/daily plus metformin (max 2000 mg/daily); 7 patients required additional therapy with insulin.

Results: As well documented in the literature, the efficacy of the dapagliflozin/metformin combination in the treatment of DM patients with NAFLD was shown in our series. Improvements in glycemic indices (HbA1c- 7.17 ± 0.16vs. 7.05 ± 0.18; FPG - 10.85 ± 0.48vs. 9.39 ± 0.46,р < 0.05), a reduction of BMI (31.04 ± 0.63kg/m2vs. 29.55 ± 0.50kg/m2, р < 0.05) and in liver function (AST/ALT 0.83 ± 0.05vs. 0.74 ± 0.05) observed during the long-term (16 months) administration of these drugs. The NAFLD, FIB-4 and APRI scales were used to determine the risk of liver fibrosis in this group of DM patients. After the start of the combination therapy, all scales showed decreases in the level of non-invasive liver fibrosis indices of these patients. The most sensitive method for the early diagnosis of liver fibrosis was the NAFLD scale, which decreased significantly (-0.941 ± 0.11 vs. -1.61 ± 0.12 points, р < 0,001). Following treatment, the number of patients with mild liver fibrosis increased from 8 (27.6%) to 21 (64.9%) and those in the "gray zone" also decreased from 29 (72.6%) to 13 (35.1%).

Conclusion: In this non-randomized, single treatment arm group of DM patients study, we demonstrated that following combination therapy of dapagliflozin plus metformin for 16 months, better glycemic control is accompanied by simultaneous improvements in liver function tests and superior NAFLD scale values of liver fibrosis.


O. Lavrynenko: None. N. Kravchun: None. O. Zemlianitsyna: None. I. Dunaeva: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. E. Cersosimo: None. I. Karachentsev: None.

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