Background: Individuals at high risk for type 2 diabetes are also at an increased risk for developing cardiovascular disease (CVD). Although there are separate trials examining the effects of lifestyle interventions on absolute CVD risk among people at high risk for type 2 diabetes, a comprehensive evidence synthesis of these trials is lacking.

Objective: We will systematically synthesize the evidence on the effects of lifestyle interventions in reducing absolute CVD risk and CVD risk factors among people at high risk for type 2 diabetes.

Methods: We adhered to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) statement in reporting the details of this protocol. Randomized controlled trials of diabetes prevention that examined the effects of lifestyle interventions for at least 6 months on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes will be eligible. We will systematically search the MEDLINE, Embase, PsycINFO, CENTRAL, and Scopus databases and ClinicalTrials.gov using a mix of Medical Subject Headings and text words. Two authors will independently screen the abstract and title of the articles retrieved from the search, followed by full-text reviews using the inclusion and exclusion criteria and data extraction from the eligible studies. Article screening and data extraction will be performed in the Covidence software. The primary outcome will be the changes in absolute 10-year CVD risk, as estimated by risk prediction models. The secondary outcomes are the changes in CVD risk factors, including behavioral, clinical, biochemical, and psychosocial risk factors, and incidence of type 2 diabetes.

Results: An initial database search was conducted in July 2023. After screening 1935 articles identified through the database search, 42 articles were considered eligible for inclusion. It is anticipated that the study findings will be submitted for publication in a peer-reviewed journal by the end of 2024.

Conclusions: This study will provide up-to-date, systematically synthesized evidence on the effects of lifestyle interventions on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes.

Trial registration: PROSPERO CRD42023429869; https://tinyurl.com/59ajy7rw.

International registered report identifier (irrid): DERR1-10.2196/53517.