However, the effect of weight loss through lifestyle modification on cardiovascular outcomes remains a subject of debate. The Look Action for Health in Diabetes (AHEAD) study randomly assigned 5,145 overweight or obese individuals with type 2 diabetes to either an intensive lifestyle intervention group (reduced caloric intake and increased physical activity) or a control group, with a median follow-up period of 9.6 years [7]. The intervention group experienced greater weight loss than the control group, although the difference diminished over time (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at the end of the study). Despite improved glucose control, fitness, and cardiovascular risk factors, the primary outcome (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina) did not significantly differ between the two groups (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.83 to 1.09). Interestingly, a post hoc analysis revealed that participants who lost more than 10% of their body weight in the first year had a 21% lower risk of cardiovascular events over 10 years than those with stable weight or weight gain, suggesting the importance of the magnitude of weight loss [8].

In contrast, a recent meta-analysis of 13 studies found a significantly increased risk of composite major cardiovascular events (pooled HR, 1.71; 95% CI, 1.38 to 2.12) and cardiovascular mortality (pooled HR, 1.50; 95% CI, 1.27 to 1.76) associated with major weight loss (>10%) among type 2 diabetes patients [9]. Another systematic review and meta-analysis of 14 observational studies and three clinical trials examining behavioral weight changes and cardiovascular disease in patients with type 2 diabetes showed that weight gain was linked to a significantly higher hazard of cardiovascular events and all-cause mortality compared to no weight change [10]. Moreover, behavioral interventions targeting weight loss did not demonstrate any beneficial effect on cardiovascular events. Taken together, the influence of weight loss through non-pharmacological approaches on cardiovascular outcomes remains a contentious issue.

In this issue of Endocrinology and Metabolism, a study utilizing the Rio de Janeiro Type 2 Diabetes Cohort provides valuable insights into the relationship between weight loss, physical activity, and cardiovascular events [11]. This research followed 651 individuals with type 2 diabetes for a median duration of 9.3 years. During the initial 2-year period, participants’ weight changes were assessed and categorized into groups with weight loss of 5% or more, weight loss of less than 5%, and weight gain. The researchers discovered that individuals who achieved a weight loss of 5% or more had a 48% lower risk of total cardiovascular events than those who gained weight. Notably, this study also examined the interaction between weight changes and physical activity. Among physically active participants, those who achieved a weight loss of 5% or more experienced even greater cardiovascular benefits (an 80% reduction in the risk of total cardiovascular events and a 79% reduction in the risk of major adverse cardiovascular events compared to individuals who gained weight). However, for sedentary participants, weight loss did not yield significant cardiovascular advantages. These findings hold important implications for managing individuals with type 2 diabetes. The study suggests that a weight loss goal of 5% or more, combined with regular physical activity, should be considered as a therapeutic strategy to reduce the burden of cardiovascular disease in this population. The benefits of weight loss remained consistent across various subgroups, regardless of age, sex, obesity, diabetes duration, presence of complications, or glycemic control. Nonetheless, some limitations of this study should be acknowledged. Due to the observational nature of the research, causality cannot be definitively established, and there is potential for unknown or unmeasured confounding factors. Additionally, the study cohort primarily consisted of middle-aged to elderly individuals with type 2 diabetes and pre-existing microvascular and macrovascular complications, which may limit the generalizability of the findings to other populations.

This study emphasizes the significance of establishing attainable weight loss objectives, integrating regular physical exercise, and customizing interventions based on individual patient traits. Additional research is necessary to investigate the ideal approaches and levels of sustainable weight loss, as well as to evaluate the long-term effects on cardiovascular disease and diverse health outcomes.