IntroductionDipeptidyl peptidase-4 inhibitors (DPP-4i) provide potent anti-diabetic effects in patients with type 2 diabetes mellitus (T2DM), but their role in the presence of nonalcoholic fatty liver disease (NAFLD) is not well-known. The aim of this clinical trial was to evaluate the effects of sitagliptin on the metabolic profile and liver tests in metformin-treated T2DM patients with NAFLD. Patients-MethodsThis was a prospective, 12-week, single-center, comparative randomized clinical trial (RCT) enrolling 66 adult T2DM patients with NAFLD (diagnosed by ultrasound). Patients were randomly assigned to either metformin (2000 mg/day, n=33) or sitagliptin + metformin (100 and 2000 mg/day, respectively, n=33), administered orally. Certain metabolic parameters, i.e., fasting blood sugar (FBS), hemoglobin A1c (Hb1A1c), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), vitamin D3 (vitD3), alkaline phosphatase (ALP), alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) were measured at baseline and after 12 weeks. Triglyceride-glucose (TG-G) index was also calculated. ResultsAll biochemical variables decreased by a greater extent in the sitagliptin+metformin group compared with the metformin group with differences in FBS (p=0.030), TC (p=0.017), TG (p=0.008), SGPT (p=0.018) and vitD3 (p=0.001) reaching statistical significance. Furthermore, the mean reduction of the TG-G index was significantly greater in the sitagliptin+metformin vs. metformin group (0.67 vs. 0.21, respectively; p=0.017). ConclusionSitagliptin+metformin therapy led to significantly greater improvements in FBS, TC, TG, SGPT, vitD3 and TG-G compared with the metformin monotherapy group. Other biomarkers also decreased more in the sitagliptin+metformin vs. metformin group, but these differences did not reach statistical significance. The present findings should be interpreted with caution but there are indicating certain metabolic benefits after sitagliptin addition in metformin-treated T2DM patients with NAFLD. Further studies are required to elucidate these effects and provide strong evidence for safe conclusions.