Association of Magnitude of Weight Loss and Weight Variability with Mortality and Major Cardiovascular Events Among Individuals with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis

Background: Weight management is strongly promoted for overweight or obese patients with type 2 diabetes (T2DM) by current guidelines. However, the prognostic impact of weight loss achieved without behavioural intervention on the mortality and cardiovascular (CV) outcomes in diabetic patients is still contested.

Methods: We searched the PubMed, Embase, and Cochrane Library databases for studies that investigated the association of weight loss or weight variability with mortality and CV outcomes. Results of studies that measured weight loss by percentage weight loss from baseline and stratified it as > 10% and 5-10% or studies that computed weight variability were pooled using random effects model. Study quality was evaluated using the Newcastle-Ottawa Scale.

Results: Thirty eligible studies were included in the systematic review and 13 of these were included in the meta-analysis. Large weight loss (> 10%) was associated with increased risk of all-cause mortality (pooled hazard ratio (HR) 2.27, 95% CI 1.51-3.42), composite of major CV events (pooled HR 1.71, 95% CI 1.38-2.12) and CV mortality (pooled HR 1.50, 95% CI 1.27-1.76) among T2DM patients. Moderate weight loss showed no significant association with all-cause mortality (pooled HR 1.17, 95% CI 0.97-1.41) or CV outcomes (pooled HR 1.12, 95% CI 0.94-1.33). Weight variability was associated with high hazard of all-cause mortality (pooled HR 1.54, 95% CI 1.52-1.56).

Conclusions: Large weight loss and large fluctuations in weight are potential markers of increased risk of mortality and CV events in T2DM patients. Maintaining a stable weight may have positive impact in these patients.