Randomized controlled trial of effects of metformin in NAFLD patients with newly diagnosed type 2 diabetes treated with an intensive lifestyle: a study protocol.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are common chronic diseases. The coexistence of NAFLD and diabetes accelerates the progression of both and tends to induce bad prognosis. To date, lifestyle modification has been suggested as the first-line treatment for NAFLD patients. Some studies indicated that lifestyle modification could normalize glucose levels in newly diagnosed T2DM, but many individuals do not reach glycemic targets in practice using lifestyle modification alone. Considering the tight link between NAFLD and T2DM, metformin, a widely used drug in diabetic patients with a good safety profile, may be a possible treatment or control of NAFLD progression. There is no therapeutic consensus for the treatment of NAFLD patients with diabetes. Therefore, it is essential to elucidate the beneficial effects of lifestyle modification combined with metformin on glucose-lipid metabolism in the NAFLD population with newly diagnosed T2DM.

METHODS: Participants will be recruited in this single-center, randomized clinical trial through telephone interview. All participants will be assigned randomly at a 1:1:1 ratio to three groups and treated with lifestyle modification including calorie-restricted dietary and exercise therapy, 500-2000 mg/day metformin, or treated with both lifestyle modification and 500-2000 mg/day metformin (the co-intervention group) for 12 weeks. The primary outcomes are changes in glycemic control and severity of fatty liver from baseline to 12 weeks of follow-up.

DISCUSSION: This trial is designed to clarify whether lifestyle intervention combined with metformin has synergistic effects on glycemic control, attenuating the progression of NAFLD in NAFLD patients with newly diagnosed T2DM.

TRIAL REGISTRATION: ChiCTR2300072031. Registered on 31 May 2023.