Efficacy of lifestyle weight loss interventions on regression to normoglycemia and progression to type 2 diabetes in individuals with prediabetes: a systematic review and pairwise and dose-response meta-analyses

Background: Current recommendations for weight loss in individuals with prediabetes come from individual trials and are derived from older data.

Objectives: To elucidate the dose-dependent impacts of weight loss on participants with prediabetes to determine the optimal magnitude of weight loss required for the implementation of the most effective diabetes prevention program.

Methods: We searched PubMed, Scopus, CENTRAL, CINAHL, and gray literature sources to September 2023 for randomized trials ≥6 mo that evaluated the efficacy of a lifestyle weight loss intervention on participants with prediabetes. We conducted random-effects pairwise meta-analyses to calculate relative and absolute effects. We performed a 1-stage weighted mixed-effects meta-analysis to elucidate the dose-response curves.

Results: Forty-four randomized trials with 14,742 participants with prediabetes [intervention duration range: 6-72 mo (median: 24 mo), mean weight loss range: 1%-9%] were included. Lifestyle weight loss interventions increased regression to normoglycemia by 11/100 participants (95% confidence interval [CI]: 8 more, 17 more; risk ratio: 1.51; 95% CI: 1.27, 1.80; n = 20 trials, grading of recommendations assessment, development, and evaluation = moderate], and reduced progression to type 2 diabetes by 8/100 participants (95% CI: 11 fewer, 6 fewer; risk ratio: 0.59; 95% CI: 0.51, 0.67; n = 37, grading of recommendations assessment, development, and evaluation = moderate). There were no significant or credible differences between subgroups categorized by the type and duration of intervention. Dose-response meta-analyses indicated that the risk of regression to normoglycemia increased, and the risk of progression to type 2 diabetes declined in a linear pattern within the range of weight loss from 1% to 9%.

Conclusions: Over a median duration of 24 mo, with weight loss ranging from 1% to 9%, the relationship between weight loss and the progression to type 2 diabetes, as well as the regression to normoglycemia, follows a linear pattern. Any form of lifestyle weight loss intervention, including diet, exercise, or a combination of both, can have beneficial impacts on participants with prediabetes. This trial was registered at PROSPERO as CRD42023465322.