Letter to Editor: Role of Pharmacotherapy in Patients With Coexisting Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Potential conflict of interest: Nothing to report. To the Editor: We read with interest a recent article written by Yan et al.1 The authors conducted a randomized trial in patients with coexisting type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) to receive liraglutide, sitagliptin, or insulin glargine as add‐on to metformin. The authors observed glycemic control and a reduction in body weight, intrahepatic lipid, and visceral adipose tissue in patients who received liraglutide or sitagliptin and then reported these add‐on therapies to be novel pharmacotherapeutic therapies in patients with NAFLD and T2DM. However, the clinical meaningfulness of these pharmacologic treatments has not been conclusively established, especially because histopathology was not used to diagnose and determine the severity of NAFLD in that study. Management of NAFLD consists of treatment of liver disease and its comorbidities, including T2DM. Weight loss with either lifestyle intervention or operation is the mainstay of treatment for patients with NAFLD, as it has been shown to improve histologic features of the liver in these patients.2 Previous studies assessed the efficacy of different pharmacologic treatments for NAFLD.3 These trials enrolled patients with biopsy‐confirmed nonalcoholic steatohepatitis (NASH) and used liver histology to assess improvement in histologic features, such as resolution of steatohepatitis, Kleiner fibrosis stage, and NAFLD activity score. In contrast, the Yan et al. study enrolled patients who were clinically diagnosed with NAFLD but did not disclose how many of their study patients were diagnosed by liver biopsy. This is an important factor given the recommendation that studies in pharmacologic treatments aimed primarily at improving liver disease should include only patients with biopsy‐proven NASH and fibrosis, because NAFLD without steatohepatitis or fibrosis has a better prognosis. In addition, although magnetic resonance imaging–estimated proton density fat fraction could be used to quantify changes in liver fat in clinical trials, its efficacy for detecting other features of NAFLD, such as steatohepatitis and fibrosis, is limited. In conclusion, histopathology should be used to guide the need for pharmacotherapy in NAFLD and monitor disease progression. The risks and benefits of liraglutide and sitagliptin must be carefully considered when using either of these agents in patients at risk for developing severe side effects.