Understanding the Long-Term Effects of Obesity Drugs: A Closer Look

A new generation of obesity drugs has emerged, boasting remarkable weight loss results for patients struggling with excess weight. However, a recent study published in the Journal of the American Medical Association raises concerns about the long-term effects of these drugs. The research focused on tirzepatide, the main component of Eli Lilly’s weight loss drug Zepbound, which gained US approval just last month. While the study revealed substantial initial weight loss, it also highlighted an alarming trend: much of the lost weight tends to return once patients discontinue treatment. These findings suggest that individuals may become reliant on these drugs for extended periods, raising important questions about their sustainability.

The study involved 670 adults who received weekly injections of tirzepatide over a period of 36 weeks. Astonishingly, the participants achieved an average weight loss of 20.9 percent during this time. Subsequently, the group was divided into two, with half continuing to take Zepbound while the other half received a placebo. After 88 weeks, those who had been on the placebo had regained nearly half of the weight they had lost, resulting in a 9.9 percent reduction from their initial weight. In contrast, the individuals who remained on Zepbound continued to experience weight loss, reaching a remarkable 25.3 percent reduction from their starting weight.

It is crucial to note that the study participants were predominantly women with a mean age of 48 and an average weight of 107.3 kilograms (236.6 pounds) at the beginning of the trial. Throughout the study, all participants were advised to consume 500 fewer calories per day than they burned and engage in at least 150 minutes of exercise per week. While these lifestyle modifications likely contributed to the initial weight loss, they did not prevent weight regain for those who ceased drug treatment. The researchers behind the study, led by Louis Aronne at Weill Cornell Medicine in New York, stressed the importance of ongoing pharmacotherapy to prevent weight regain and sustain long-term weight reduction.

The study also highlighted previous trials involving medications such as semaglutide, a key ingredient in Novo Nordisk’s Ozempic and Wegovy. Like Zepbound, these drugs fall into the category of “GLP-1 agonists,” which mimic the function of a hormone that regulates insulin secretion, slows down stomach emptying, and suppresses appetite. The results from these trials, combined with the recent study on tirzepatide, suggest that weight regain is a common challenge associated with discontinuing anti-obesity medications. The medical community should heed these findings and consider the impact when prescribing such medications.

Jeff Emmick of Lilly responded to the study, emphasizing that obesity is a chronic disease requiring ongoing treatment. Emmick pointed out that treatment is often ceased once weight goals are achieved, leading to a lack of understanding among patients, healthcare providers, and the general public. While GLP-1 agonists have shown promising results in reducing the risk of cardiovascular disease related to obesity, they have also been associated with an increased risk of gastrointestinal issues. Although severe complications are rare, experts worry about the potential long-term risks of using these drugs for years or even decades, especially considering the cost implications. Zepbound, for example, can cost $1,059.87 per month, and many insurance companies do not cover weight loss medications. Furthermore, Medicare, the subsidized insurance for the elderly, is explicitly prohibited from covering these drugs.

The study exploring the long-term effects of obesity drugs provides important insights into the challenges of weight maintenance. While these medications offer significant initial weight loss, patients may experience weight regain once treatment is discontinued. This research underscores the need for ongoing pharmacotherapy and highlights the complexities of managing obesity as a chronic disease. Moving forward, healthcare providers must carefully consider the sustainability and potential risks associated with anti-obesity medications when developing comprehensive treatment plans for individuals living with obesity.