Reasons Why Many Discontinue Popular Weight-Loss Medications（3/3）

Mutsuko Ohnishi, MD

Internal medicine physician in Boston, USA

Following up on our previous article, we're diving back into the conversation about the trending weight loss medications. In the United States, Novo Nordisk's obesity treatment drug Semaglutide (brand name Wegovy), Semaglutide for type 2 diabetes with weight loss effects (brand name Ozempic, which has a lower dose of Semaglutide than Wegovy), and Eli Lilly's type 2 diabetes treatment drug with weight loss effects, Tirzepatide (brand name Mounjaro), are currently popular. But, how many people can lose how much weight and over what duration with these treatments? And, what's the difference in effectiveness between Semaglutide and Tirzepatide? A paper answering these questions was reported in November 2023, although it is yet to be peer-reviewed.

Tirzepatide vs. Semaglutide: Which is More Effective for Weight Loss?

Truven Health Analytics, a data analysis company owned and operated by 30 US healthcare systems, collected data from a large population to compare these two drugs. Notably, this research did not receive any pharmaceutical company support.

The study began with over 40,000 overweight or obese patients who started treatment with either Semaglutide or Tirzepatide between May 2022 and September 2023. 52% had type 2 diabetes, and the remaining 48% had no diabetes recorded in their medical history, leading researchers to infer that these drugs were probably prescribed off-label for weight loss alone, according to CNN.

A year after starting treatment, Tirzepatide showed more significant weight loss effects than Semaglutide.

• Over 5% weight loss: 82% in the Tirzepatide group vs. 65% in the Semaglutide group

• Over 10% weight loss: 62% in the Tirzepatide group vs. 38% in the Semaglutide group

• Over 15% weight loss: 42% in the Tirzepatide group vs. 19% in the Semaglutide group

Both drugs reported similar gastrointestinal side effects during the trial. However, this study was limited to doses approved for treating type 2 diabetes, which may limit its conclusions. The US Food and Drug Administration (FDA) has approved high doses of Tirzepatide (brand name Zepbound) and Semaglutide (brand name Wegovy) for weight loss.

Interestingly, the longer the treatment duration, the greater the weight loss. Yet, 55% of study participants (55.7% for Tirzepatide, 54.4% for Semaglutide) discontinued their treatment during the study. Researchers stated, "Patients who achieved the desired weight loss were more likely to continue treatment. In contrast, those who did not see weight changes were more likely to stop or change their treatment," adding that "Drug shortages and difficulties in obtaining the medication might have occurred during the trial period."

A Surprisingly Large Number of People Discontinue Treatment

In addition to the above findings, Reuters reports that analysis of insurance company data revealed less than one in three patients who began weight loss drugs for that purpose continued beyond one year.

One reason people might stop using weight-loss medications is the misunderstanding that the drugs are ineffective. Many have high hopes for the "long-term effectiveness" of these medications. However, indefinite weight loss leading to dangerously thin conditions is unrealistic. No matter the method—diet, fitness, or bariatric surgery—everyone eventually reaches a weight loss plateau, including with Semaglutide and Tirzepatide. Rapid weight loss is seen after starting these medications, but it eventually plateaus.

A 2022 report in "Nature Medicine" by Dr. W. Timothy Garvey from the Department of Nutrition Sciences at the University of Alabama at Birmingham found that people taking Semaglutide reached a weight loss plateau approximately 60 weeks after starting the medication.

The reasons for this plateau are unclear, including "the body's attempt to maintain weight to protect against starvation," "metabolism slowing down with rapid weight loss," "the body conserving energy by making it harder to burn calories," and "increased tolerance to the medication requiring higher doses to continue losing weight."

Discontinuing treatment leads to weight regain and potentially worsens controlled diabetes or hypertension. According to a 2022 report by Dr. John P.H. Wilding from the University of Liverpool, patients saw an average of 17.3% weight loss during 68 weeks of Semaglutide treatment, but two-thirds of the weight loss returned one year after stopping the treatment. Blood pressure and blood sugar levels also began reverting to pre-treatment levels.

Weight Cycling Increases the Risk of New Diseases

Weight cycling, the repeated loss and regain of weight, also known as "yo-yo dieting" when caused by diet could potentially lead to serious impacts on both physical and mental health. Repetitive dieting or weight cycling might increase the risks of eating disorders, other mental health issues, obesity, type 2 diabetes, hypertension, cancer, fractures, and even a higher mortality rate.

Weight Loss Medications Are Not Miracle Cures; Effort and Dedication Required

As per NBC News (8), while drugs like Ozempic, prescribed for type 2 diabetes and off-label for weight loss, are blockbusters, very few patients continue them for years. Interviews with seven individuals who have been using Ozempic for one and a half to two and a half years revealed a consensus: Ozempic is not a shortcut to health. They note that although the medication helps in reducing weight or lowering blood sugar levels (or both, varying by individual), maintaining these changes requires effort.

Barbie Jackson-Williams, a 54-year-old resident of Iowa, started Ozempic treatment in early 2021 for weight loss and type 2 diabetes management. She noted, "Thanks to this medication, I was able to switch from pasta, a long-time favorite, to low-fat proteins and reduce sweetened iced coffee from my diet – changes that felt impossible before." "However, there are people using this medication just to lose weight, which is a mistake. They fail to realize it requires genuine effort."

Edward Matias, a 45-year-old IT professional from Connecticut, emphasized, "This is not a panacea. It's not the fountain of youth. It requires effort and dedication. Those who think they can eat anything because they're on this medication are sorely mistaken." "Despite the medication, I still need to be mindful of consuming sugar and carbs because of my diabetes. During my treatment with Ozempic, my weight dropped from about 140 kg to 104 kg."

Most of the interviewees agreed that rather than being a cure-all, Ozempic facilitated lifestyle changes, enabling them to exercise in ways they couldn't before.

Jackson-Williams added, "Losing weight made me feel more energetic, and I find myself sitting still less. I want to be active. I want to do things. I can't just sit and watch TV like I used to."

Dr. Eduardo Grunvald, an obesity medicine specialist at the University of California, San Diego, stated, "These medications should be used alongside lifestyle improvements. While treating with these drugs, it's essential to pay attention to your diet and exercise. That's what these medications are intended for."

Despite the popularity of these weight-loss drugs, discontinuing treatment based on self-judgment could lead to weight regain and worsening of diabetes or hypertension. Falling into weight cycling could nullify all efforts. Just as patients with chronic conditions like hypertension or diabetes might need lifelong medication, obesity treatment could also be a lifelong commitment for many. However, some patients might be able to discontinue the medication alongside improvements in their lifestyle. In such cases, monitoring changes in blood pressure, blood sugar levels, and other indicators through medical consultation becomes crucial.

This article is a translation of Japanese MRIC published on Jan 9, 2024