Drugs like Ozempic, Wegovy, Mounjaro, and Zepbound have the potential to improve the health of millions of people with obesity and obesity-related diseases, but there are multiple factors to consider in deciding whether to use these drugs, including their cost, their immediate effects, and the dearth of evidence on their long-term effects. We discussed those considerations in our past three posts in this series. This post focuses on other key factors to consider in deciding whether to make these drugs part of a weight-loss plan.

Pharmacotherapy vs. Bariatric Surgery

Weight-loss drugs offer a non-invasive intervention that can result in considerable weight loss and potentially fewer serious side effects compared to bariatric surgery. However, in some instances bariatric surgery may be a preferable treatment option, particularly if insurance coverage or cost (discussed in the third installment of this series) presents a barrier to using weight-loss drugs.

In some studies of diabetic patients, bariatric surgery has been shown to result in better blood sugar control, less diabetic medication usage, and a higher rate of diabetes remission than medical or lifestyle interventions. However, studies demonstrating better outcomes with surgery have not included the newer classes of weight-loss drugs. Bariatric surgery has also been shown to be an effective option for weight loss, but it can lead to a range of complications including nutritional deficiencies, gallstones, dumping syndrome (a collection of symptoms that can occur when your stomach dumps food too fast into your small intestine), bowel obstruction, and infection.

As with weight-loss drugs, insurance coverage for bariatric surgery varies. The setting in which the procedure is performed also varies. In 2021, most bariatric surgeries were performed in the inpatient setting (86%). The average inpatient bariatric surgery cost was $32,868, including the average amount paid by the health plan ($31,441) and the average out-of-pocket cost paid by the patient ($1,427). The remaining 14% of bariatric surgeries occurred in the outpatient setting, with an average cost of $22,675, including the average cost paid by the health plan ($21,046) and the average out-of-pocket cost paid by the patient ($1,629).

For comparison, in 2021, the average cost for a one-month supply of semaglutide was $831 (nearly $10,000 per year), including the average cost paid by the health plan ($765) and the average out-of-pocket cost ($66). Because it is common to regain weight once the treatment is discontinued, long-term and possibly indefinite use of these drugs may be necessary.

In some cases, a combination of surgery and pharmacotherapy is used to help people maintain their weight loss.

Nutritional Problems and Lean Body Mass Loss 

A healthy diet includes proper amounts of calories, quality protein, vitamins, minerals, and other nutrients. As discussed in the first installment of this series, drugs like Wegovy and Zepbound work, in part, by reducing appetite and consumption while also delaying how fast the stomach empties. Insufficient food intake or poor food choices can lead to inadequate intake of important nutrients.

When weight loss is achieved through a calorie-reduced diet, a portion of that weight loss comes from loss of lean body mass. Lean body mass includes non-fatty tissues such as muscle, bone, and organs. Losing muscle, and not just fat, is to be expected when consuming fewer calories, but this muscle loss could cause problems, particularly for older adults. Generally, muscle mass decreases with age. The more muscle someone over the age of 65 loses, the greater their risk of becoming frail or suffering a fall — the leading cause of injury for adults ages 65 and older — making it crucial for older adults to maintain muscle mass.

In a subgroup of participants studied during a clinical trial of semaglutide, participants lost an average of 23 pounds of fat mass and 15 pounds of lean body mass, including muscle and other non-fatty tissues. Individuals in a tirzepatide clinical trial saw, on average, a 40% reduction of total fat mass and an 11% reduction in total lean body mass.

At-Risk populations

According to the prescribing information for Wegovy and Zepbound, patients are advised to discontinue use of the drugs if they become pregnant. The prescribing information notes that studies suggest there may be potential risks to the fetus from exposure to the drugs. To help healthcare providers, patients, and researchers better understand the safety of weight-loss drugs during pregnancy, Novo Nordisk has established the Wegovy Pregnancy Registry. Eli Lilly is developing a similar registry for Zepbound.

Because of the potential for fetal harm, patients are encouraged to discontinue Wegovy at least two months before they plan to become pregnant. Additionally, the use of Zepbound may reduce the efficacy of oral hormonal contraceptives because of delayed gastric emptying.

Wegovy and Zepbound should not be used if a patient has a personal or family history of thyroid cancer or an endocrine system condition called multiple endocrine neoplasia type 2, also known as MEN 2.

Although Wegovy has been approved by the U.S. Food and Drug Administration for children age 12 and older, authorities are mixed on providing these drugs to children and adolescents, with some citing concerns over the lack of data on safety and efficacy (as discussed in the second installment of this series).

Discontinuing Use and Long-Term Use

Reasons cited by patients for discontinuing the use of weight-loss drugs include side effects, affordability, or limited drug availability. In a semaglutide clinical trial, about 7% of the study population discontinued treatment during the 68-week trial period due to adverse events (mainly related to gastrointestinal issues). In a 72-week tirzepatide clinical trial, discontinuations due to adverse events ranged from 4% to 7%, depending on the dose. A study analyzing electronic health records found that the majority of patients discontinued the use of weight-loss medications within one year. Clinical trials for semaglutide (Wegovy) and tirzepatide (Zepbound) have shown that long-term use is necessary to maintain the benefits of using these drugs and that patients tend to regain much of the weight they lost when they discontinue treatment.

The Bottom Line

When deciding whether to take a weight-loss drug, it is important to weigh the risks of the medication against the risks associated with being overweight or obese. Medications like Ozempic, Wegovy, Mounjaro, and Zepbound are effective for losing weight. However, there are many other factors to consider, and the long-term effects are still unknown. Ultimately, the decision to use weight-loss drugs should be made in consultation with a healthcare provider, taking into consideration individual health needs, risks, and benefits.

In our fifth and final post in this series, we will review the history of weight-loss drugs in the U.S. and consider what the future of obesity treatment may look like.