Evaluating the Safety and Efficacy of Sodium-Glucose Co-transporter 2 Inhibitors in Subjects with Prediabetes: A Protocol for a Randomized Controlled Trial.

Introduction: Prediabetes is a state of subclinical glycemic impairment, bridging normal glucose tolerance and diabetes. Globally, over 30% of individuals exhibit prediabetic conditions, with a significant proportion progressing to diabetes. Prediabetes augments risks of various diseases including cardiovascular and kidney disease. While interventions like lifestyle changes have shown promise in diabetes prevention, their long-term sustainability is challenging. Alternative pharmacological treatments, such as acarbose and metformin, have demonstrated efficacy in certain populations. Sodium-glucose co-transporter 2 inhibitors, a novel class of glucose-lowering agents, have shown potential benefits for heart and kidney health in patients with diabetes. This research aims to evaluate the effectiveness and safety of dapagliflozin in individuals with prediabetes, elucidating its potential role in diabetes prevention strategies.

Research design and methods: This prospective trial is being conducted at Peking University Third Hospital. A total of 240 participants with prediabetes will be enrolled and randomly divided into two groups: one receiving dapagliflozin (10 mg/day) with lifestyle education, and the other with lifestyle education alone over a 12-week duration (with male/female = 1:1 in each group). Anthropometric, clinical and laboratory tests, including body mass index, waist circumference, fasting blood glucose, oral glucose tolerance test, insulin, lipid profile, liver and kidney function, sperm quality, will be conducted at the onset and conclusion of the trial. For adherence monitoring, participants will receive phone follow-ups at week 4 and week 8. The primary outcome is the change in 2-h plasma glucose during an oral glucose tolerance test over the study duration. Secondary outcomes encompass changes in various health metrics, including body mass index, lipid profiles, and liver function.

Planned outcomes: The proposed study is set to refine diabetes prevention strategies on the basis of its potential benefits observed in patients with diabetes.

Conclusions: This will be the first randomized controlled trial to evaluate the safety and effectiveness of sodium-glucose co-transporter 2 inhibitors compared with lifestyle education for individuals with prediabetes.

Trial registration: ClinicalTrials.gov identifier NCT05914857 (registered 24 July 2023).