PURPOSE OF THE REVIEW: Incretin mimetic drugs (IMDs) induce rapid weight loss and improve cardiometabolic health. However, over 50% of users discontinue and then reinitiate therapy within two years. This drug cycling drives weight loss-regain cycling, which adversely affects body composition and metabolic health. RECENT FINDINGS: Cessation of IMD therapy leads to a rapid and near-complete reversal of weight loss and cardiometabolic improvement within one year and early IMD discontinuation is associated with increased cardiometabolic risk. Concerningly, up to 40% of the weight lost on these therapies is attributed to lean mass loss. Weight cycling compounds these effects and may worsen body composition and metabolic profiles beyond baseline. Supervised exercise programmes attenuate weight regain and may have a lasting 'legacy' effect on metabolic markers. SUMMARY: The benefits of IMDs are short-lived following drug cessation and the loss of lean mass that occurs with IMDs may increase the risk of sarcopenia. Incorporating supervised exercise programmes during and after therapy may preserve lean mass, promote healthier body composition and attenuate some of the observed metabolic rebound. Clinicians should weigh the risks and benefits of short-term, or cyclical use of IMDs, particularly in those with low initial muscle mass reserves or metabolically vulnerable cohorts.
Alexander et al. (Thu,) studied this question.