Lifestyle modification may outperform medications over time for diabetes prevention in at-risk adults, meta-analysis finds

The risk difference between lifestyle modification and medication studies was 4 cases per 100 person-years, and 25 people would need to be treated with lifestyle modification to prevent one diabetes case.


For diabetes prevention, lifestyle modification strategies may provide better long-term effects than medications after active treatment is discontinued, although their effects seem to lessen over time, a recent meta-analysis found.

The analysis included 43 randomized clinical trials that evaluated lifestyle modification and medication interventions (>6 months) for diabetes prevention in at-risk adults (49,029 participants; mean age, 57.3 years; 48.0% men). Overall, 19 studies tested medications, 19 evaluated lifestyle modifications, and five tested a combination of the two interventions.

The main outcome was aggregate relative risks of diabetes in treatment versus control participants. Researchers stratified treatment subtypes (e.g., lifestyle modification components, medication classes) and, to estimate sustainability, assessed post-washout and follow-up relative risks for medications and lifestyle modifications, respectively.

Results were published online on Nov. 6 by JAMA Internal Medicine.

Overall results at the end of both interventions were similar. Lifestyle modification interventions (mean, 2.6 years; range, 0.5 to 6.3 years) were associated with a relative risk reduction of 39% (relative risk, 0.61; 95% CI, 0.54 to 0.68), and medication interventions (mean, 3.1 years; range, 1.0 to 6.3 years) were associated with a relative risk reduction of 36% (relative risk, 0.64; 95% CI, 0.54 to 0.76). The risk difference between lifestyle modification and medication studies was 4.0 cases (95% CI, 1.8 to 6.3) per 100 person-years, and 25 people would need to be treated with lifestyle modification to prevent one diabetes case.

The treatment subtypes that achieved the largest diabetes risk reductions were combined diet and physical activity programs (relative risk, 0.59; 95% CI, 0.51 to 0.69), weight-loss medications (orlistat and combination phentermine-topiramate; relative risk, 0.37; 95% CI, 0.22 to 0.62), and insulin sensitizers (metformin, rosiglitazone, and pioglitazone; relative risk, 0.47; 95% CI, 0.32 to 0.68).

However, the effect of medications did not persist at the end of the washout or follow-up period in studies reporting this data. Lifestyle modification studies (mean follow-up, 7.2 years; range, 5.7 to 9.4 years) showed a relative risk reduction of 28% (relative risk, 0.72; 95% CI, 0.60 to 0.86), whereas medication studies (mean follow-up, 17 weeks; range, 2 to 52 weeks) showed no sustained relative risk reduction (relative risk, 0.95; 95% CI, 0.79 to 1.14).

The authors noted limitations to the review, including a high level of heterogeneity in treatment effects and variance in the definitions of diabetes used in the trials.

“Overall, [lifestyle modification] strategies provide better long-term effects than medications, although strategies to sustain intervention effects are needed,” the authors wrote. “As intervention effects decrease over time, future research should identify cost-effective, successful maintenance strategies to prevent or delay progression to diabetes.”