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Original Investigation
December 2017

Long-term Sustainability of Diabetes Prevention Approaches: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Author Affiliations
  • 1Division of Endocrinology, Metabolism and Lipids, School of Medicine, Emory University, Atlanta, Georgia
  • 2Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia
  • 3CommUnityCare Health Centers, Austin, Texas
  • 4Division of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta
  • 5Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
  • 6Department of Family and Preventive Medicine, Emory University, Atlanta, Georgia
JAMA Intern Med. 2017;177(12):1808-1817. doi:10.1001/jamainternmed.2017.6040
Key Points

Questions  How much do primary prevention strategies reduce the risk of conversion from prediabetes to diabetes, and are initial effects sustained over the long term?

Findings  In this meta-analysis of randomized clinical trials including 49 029 participants, lifestyle modification and medications promoting weight loss or insulin sensitization were associated with reduced diabetes risk by 36% to 39%. Effects of medications were not sustained after they were discontinued; effects of lifestyle modification, however, were sustained after intervention was stopped, although the effects waned over time.

Meaning  For individuals at risk for diabetes, healthy lifestyle changes, weight loss, or use of insulin-sensitizing medications slow the progression to diabetes similarly; lifestyle modification strategies are better in the long term, although strategies to maintain their effects are needed.


Importance  Diabetes prevention is imperative to slow worldwide growth of diabetes-related morbidity and mortality. Yet the long-term efficacy of prevention strategies remains unknown.

Objective  To estimate aggregate long-term effects of different diabetes prevention strategies on diabetes incidence.

Data Sources  Systematic searches of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases. The initial search was conducted on January 14, 2014, and was updated on February 20, 2015. Search terms included prediabetes, primary prevention, and risk reduction.

Study Selection  Eligible randomized clinical trials evaluated lifestyle modification (LSM) and medication interventions (>6 months) for diabetes prevention in adults (age ≥18 years) at risk for diabetes, reporting between-group differences in diabetes incidence, published between January 1, 1990, and January 1, 2015. Studies testing alternative therapies and bariatric surgery, as well as those involving participants with gestational diabetes, type 1 or 2 diabetes, and metabolic syndrome, were excluded.

Data Extraction and Synthesis  Reviewers extracted the number of diabetes cases at the end of active intervention in treatment and control groups. Random-effects meta-analyses were used to obtain pooled relative risks (RRs), and reported incidence rates were used to compute pooled risk differences (RDs).

Main Outcomes and Measures  The main outcome was aggregate RRs of diabetes in treatment vs control participants. Treatment subtypes (ie, LSM components, medication classes) were stratified. To estimate sustainability, post-washout and follow-up RRs for medications and LSM interventions, respectively, were examined.

Results  Forty-three studies were included and pooled in meta-analysis (49 029 participants; mean [SD] age, 57.3 [8.7] years; 48.0% [n = 23 549] men): 19 tested medications; 19 evaluated LSM, and 5 tested combined medications and LSM. At the end of the active intervention (range, 0.5-6.3 years), LSM was associated with an RR reduction of 39% (RR, 0.61; 95% CI, 0.54-0.68), and medications were associated with an RR reduction of 36% (RR, 0.64; 95% CI, 0.54-0.76). The observed RD for LSM and medication studies was 4.0 (95% CI, 1.8-6.3) cases per 100 person-years or a number-needed-to-treat of 25. At the end of the washout or follow-up periods, LSM studies (mean follow-up, 7.2 years; range, 5.7-9.4 years) achieved an RR reduction of 28% (RR, 0.72; 95% CI, 0.60-0.86); medication studies (mean follow-up, 17 weeks; range, 2-52 weeks) showed no sustained RR reduction (RR, 0.95; 95% CI, 0.79-1.14).

Conclusions and Relevance  In adults at risk for diabetes, LSM and medications (weight loss and insulin-sensitizing agents) successfully reduced diabetes incidence. Medication effects were short lived. The LSM interventions were sustained for several years; however, their effects declined with time, suggesting that interventions to preserve effects are needed.