Effectiveness of Metformin Prolonged-Release Formulation on Achievement of Optimal Glycemic Control in Gestational Diabetes Mellitus: Protocol for a Pilot, Randomized, Double-Blind, Clinical Trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy. Optimal glycemic control is key to reducing the risk of adverse pregnancy outcomes. If glycemic control is inadequate, additional medications are needed. A large body of evidence has shown that metformin is an effective medication for GDM. Compared to the immediate-release formulation, the prolonged-release (PR) formulation of metformin offers some advantages with a single daily dose and has less frequent side effects, leading to better compliance. To date, no study has specifically reported the effectiveness of metformin PR in the treatment of GDM or the time required to achieve glycemic control after treatment. The results will help clinicians plan a better choice of treatment and follow-up for women with GDM and inadequate glycemic control. OBJECTIVE: This study aims to evaluate the effectiveness of metformin PR in the treatment of GDM in terms of achieving glycemic control within 6 weeks, time to achieve glycemic control, and associated factors. METHODS: A randomized, double-blind, placebo-controlled clinical trial will be conducted among 80 pregnant women diagnosed with GDM who had inadequate glycemic control at a university hospital in Thailand. The women will be randomized into 2 equal groups, receiving either metformin PR or a placebo in addition to nutritional therapy and behavioral modification. Dosage adjustment will be made every 2 weeks. If the glycemic target is not achieved within 6 weeks, insulin therapy will be initiated. All the participants and the investigators are blinded to the treatment provided. The primary outcome is the rate of achievement of glycemic control, and secondary outcomes are time to achieve glycemic control, rate of insulin therapy, and factors associated with the success of metformin PR use. RESULTS: The study was funded in May 2025 when recruitment started. The study is projected to be completed in October 2026. Women with GDM who experienced inadequate glycemic control by nutritional therapy were assessed for eligibility. As of October 2025, 24 women with GDM agreed to participate and follow-ups were scheduled. The results are expected to be published in 2027. CONCLUSIONS: The results of this study will provide additional information on the use of metformin in the treatment of GDM, including the use of different formulations, rate of glycemic control, time to achieve glycemic control, and associated factors. This will help physicians better plan care for pregnant women with GDM, especially when glycemic control is inadequate, including choices of metformin formulation and dosage, follow-up schedule, and identification of women at risk of treatment failure. TRIAL REGISTRATION: Thai Clinical Trial Registry TCTR20250525007; https://www.thaiclinicaltrials.org/show/TCTR20250525007. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/79855.