There is no doubt, that we are living in a new and revolutionary era of obesity care. The new class of drugs, termed GLP1RA, present a milestone in drug development, finally allowing doctors to prescribe medication, that will effectively help patients manage obesity. However, one question that often comes up, is what happens, when patients can either no longer access, afford or take the drug.
In their 2022 study published in Diabetes, Obesity, and Metabolism, Wilding et al. explored the effects of discontinuing semaglutide ("Ozempic/Wegovy"), a glucagon-like peptide-1 (GLP-1) analogue, on weight and cardiometabolic health. This study, an extension of the STEP 1 trial, sheds light on the chronic nature of obesity and the necessity of sustained intervention for long-term success in weight management.
Semaglutide had shown remarkable results during the 68-week treatment phase of the STEP 1 trial, with participants experiencing significant weight loss averaging 17.3%. Alongside weight reduction, improvements were seen in blood pressure, glycemic control, and lipid profiles. However, the 52-week off-treatment extension revealed a stark reality: without continued pharmacotherapy, participants regained about two-thirds of their lost weight, with cardiometabolic parameters reverting toward baseline levels.
Interestingly, participants who achieved the greatest weight loss during treatment experienced the most significant regain upon withdrawal. The findings underscore a physiological challenge: the body’s compensatory mechanisms strongly resist sustained weight loss, making ongoing pharmacological or lifestyle interventions essential.
Despite the challenges of weight regain, residual benefits in some cardiometabolic markers, such as triglycerides and cholesterol levels, persisted one year after treatment cessation. This suggests that even partial maintenance of weight loss can have meaningful health benefits.
The study highlights an essential truth about obesity: it is a chronic, complex disease that requires long-term management. Semaglutide offers a powerful tool in the fight against obesity, but like other pharmacotherapies, its benefits are contingent on sustained use. The trial’s findings have implications for treatment protocols, emphasizing the need for ongoing support—whether through continued medication, structured lifestyle interventions, or both. It also raises significant questions regarding the cost-effectiveness of lifelong medication versus a single intervention, such as bariatric surgery for the management of obesity.
Oliver's Thoughts
Weight Regain and Evolutionary Biology: This study is a testament to our biology’s resistance to change. Evolution has hardwired us to conserve energy and store fat, making sustained weight loss a battle against nature itself.
The Power and Limits of Semaglutide: While semaglutide offers remarkable results, it’s clear that no "magic pill" exists. Obesity management must be seen as a lifelong journey, not a temporary fix.
Hope in Partial Success: Even partial retention of weight loss can improve health markers, underscoring the value of persistence. Every bit of progress matters in the broader fight against obesity.
Wilding et al.'s research reinforces the importance of long-term strategies in addressing obesity, blending medical innovation with an understanding of human physiology. Semaglutide is a tool, not a cure—but in the right hands, it can be transformative. I think the advent of the new class of anti-obesity medication represents a revolution in our care for patient's suffering from obesity, yet the requirement for life-long therapy does raise serious questions regarding cost-effectiveness of the drugs versus for example metabolic/bariatric surgery. Watch this space!
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