Clinician Article

Long-term Effect of Lifestyle Interventions on the Cardiovascular and All-Cause Mortality of Subjects With Prediabetes and Type 2 Diabetes: A Systematic Review and Meta-analysis.

  • Zucatti KP
  • Teixeira PP
  • Wayerbacher LF
  • Piccoli GF
  • Correia PE
  • Fonseca NKO, et al.
Diabetes Care. 2022 Nov 1;45(11):2787-2795. doi: 10.2337/dc22-0642. (Review)
PMID: 36318674
Read abstract
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 6/7
  • Endocrine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Cardiology
    Relevance - 4/7
    Newsworthiness - 3/7


BACKGROUND: Lifestyle interventions improve the metabolic control of individuals with hyperglycemia.

PURPOSE: We aimed to determine the effect of lifestyle interventions on cardiovascular and all-cause mortality in this population.

DATA SOURCES: Searches were made through MEDLINE, Cochrane CENTRAL, Embase, and Web of Science (no date/language restriction, until 15 May 2022).

STUDY SELECTION: We included randomized clinical trials (RCTs) of subjects with prediabetes and type 2 diabetes, comparing intensive lifestyle interventions with usual care, with a minimum of 2 years of active intervention.

DATA EXTRACTION: Data from the 11 RCTs selected were extracted in duplicate. A frequentist and arm-based meta-analysis was performed with random-effects models to estimate relative risk (RR) for mortality, and heterogeneity was assessed through I2 metrics. A generalized linear mixed model (GLMM) was used to confirm the findings.

DATA SYNTHESIS: Lifestyle interventions were not superior to usual care in reducing cardiovascular (RR 0.99; 95% CI 0.79-1.23) or all-cause (RR 0.93; 95% CI 0.85-1.03) mortality. Subgroup, sensitivity, and meta-regression analyses showed no influence of type of intervention, mean follow-up, age, glycemic status, geographical location, risk of bias, or weight change. All of these results were confirmed with the GLMM. Most studies had a low risk of bias according to the RoB 2.0 tool and the certainty of evidence was moderate for both outcomes.

LIMITATIONS: Most studies had a low risk of bias according to the RoB 2.0 tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach resulted in moderate certainty of evidence for both outcomes. Differences in lifestyle programs and in usual care between the studies should be considered in the interpretation of our results.

CONCLUSIONS: Intensive lifestyle interventions implemented so far did not show superiority to usual care in reducing cardiovascular or all-cause mortality for subjects with prediabetes and type 2 diabetes.

Clinical Comments


The article is helpful to both subspecialists like myself (as an endocrinologist) and to those in general practice or general medicine as it attempts to provide long-term and outcome-based evidence on the benefits of lifestyle modification. The results are disappointing as the systematic review and meta-analysis showed that LSM has no impact on all-cause mortality and cardiovascular mortality. This does not necessarily mean that these interventions have no health benefits. Other outcomes that may be the result of diabetes prevention such as prevention of retinopathy or kidney disease leading to dialysis were not included in this analysis. Although the results were disappointing, it has to be acknowledged that the study was well conducted. Perhaps one issue that should be discussed is the long-term compliance that would typically wane after the first few years or even months of its initiation. This could have accounted for the lack of benefit of LSM.

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