Body weight variability as a factor of cardiovascular risk

Obesity is the most significant risk factor for a cardiovascular condition that requires efficient management. Real-world clinical practice regarding lifestyle modification (LM) demonstrates bounded potential both in weight loss and weight maintenance. This lays a cornerstone of significant body weight fluctuations (variability) when inability to maintain achieved body weight leads to its regain associated with repeated cycles of «weight loss/gain». High body weight variability undermines various organs and systems, increases incidence of any coronary/ cardiovascular event and mortality risk, elevates a risk of myocardial infarction and stroke, and enhances a risk for incident type 2 diabetes mellitus. In a cohort of patients with type 2 diabetes mellitus, significant body weight variability is significantly associated with a higher risk of macro- and microvascular complications. Furthermore, a retrospective analysis from the DCCT/EDIC study in patients with type 1 diabetes mellitus revealed a direct correlation between higher body weight variability and an increased risk of renal events. Such evidence allows us to identify body weight variability as a factor associated with cardiovascular risk, and it is necessary to prioritize weight-loss strategies that mitigate it. They include regular physical activity (both aerobic and resistance trainings), caloric restriction, and metabolic surgery. Today, GLP-1 receptor agonist therapy (in particular, semaglutide 2.4 mg) is one of the most promising strategies of simultaneously conservative, persistent (up to 4 years) and efficient weight loss. However, semaglutide withdrawal (see the STEP-1 trial) led to a loss of the treatment effect (from -17.3% [the best value] to -5.6% of baseline body weight) associated with worse cardiometabolic parameters. Thus, this further highlights body weight variability as a risk factor of cardiovascular complications. Keywords: obesity, body weight variability, semaglutide, GLP-1 receptor agonist, type 2 diabetes mellitus, IHD, cardiovascular risk. For citation: Salukhov V.V., Yudina A.F. Body weight variability as a factor of cardiovascular risk. RMJ. 2025;2:14–20. DOI: 10.32364/2225- 2282-2025-2-3