Primary care doctors warn patients not to get caught up in Wegovymania.
The American public is jazzed about Wegovy, Ozempic, Mounjaro and Zepbound for their potential for weight loss. Their primary care physicians? Not so much.
Drugs such as these are not miracle cures for obesity, clinicians say. They often come with intolerable side effects, they cost a lot of money, and when people stop using them (which many do), they will likely gain back the weight they lost. Perhaps most important, these drugs deliver best results only when accompanied by increased physical activity and a reduced-calorie diet.
In a recent Harvard publication, Walter Willett, professor of nutrition at the Harvard T. H. Chan School of Public Health, laid out two pathways ahead. “On one, the new drugs help people with severe obesity lose meaningful amounts of weight, which then increases chances of success of lifestyle-based approaches. On the other, people don’t improve their diet, don’t increase exercise, and use the drugs to counter unhealthy habits they maintain and that may have contributed to the problem. On this path, people’s health would still be poor because good lifestyles contribute to well-being in many ways unrelated to weight control.”
“Patients do come in after seeing TV and magazine ads and talking with neighbors and friends about Wegovy and Ozempic,” says Karen Smith, M.D., FAAFP, a family physician in Raeford, North Carolina, and a board member of the American Academy of Family Physicians. “They want to lose weight, and they believe this new miracle drug will help. We have a discussion with them and ask, ‘What else have you done about weight?’”
Given that approximately 70% of American adults have obesity or are overweight, conversations such as these between primary care physicians and their patients are likely to multiply. Some Wall Street analysts predict a potential $150 billion to $200 billion opportunity for the makers of these drugs.
The red carpet
The key component of many weight-loss drugs – semaglutide – belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists, according to the FDA. It mimics the GLP-1 hormone that is released in the gastrointestinal tract in response to eating. One role of GLP-1 is to prompt the body to produce more insulin, which reduces blood glucose. In higher amounts, GLP-1 also interacts with the parts of the brain that reduce appetite and signal a feeling of fullness.
Ozempic injection and Rybelsus tablets are approved by the FDA to lower blood sugar levels in adults with type 2 diabetes mellitus, in addition to diet and exercise. Ozempic is also approved to reduce the risk of heart attack, stroke, or death in adults with type 2 diabetes mellitus and known heart disease. Wegovy injection was approved for weight loss in 2021 and is simply a higher dose of semaglutide than Ozempic.
The newest entrant in the weight-loss derby is another injectable – Zepbound from Eli Lilly and Co. Zepbound was approved by the FDA in November for chronic weight management in adults with obesity (body mass index of 30 or greater) or overweight (body mass index of 27 or greater) with at least one weight-related condition (such as high blood pressure, type 2 diabetes or high cholesterol), in addition to a reduced calorie diet and increased physical activity. Tirzepatide, the active ingredient in Zepbound, had previously been FDA-approved under the trade name Mounjaro to help improve blood sugar in adults with type 2 diabetes.
Do they work?
Overall these compounds have shown to help patients shed 10% to 22% of body weight in their first year of use, according to Harvard nutrition expert Willett. In its January 2021 approval of Wegovy, the FDA reported that its manufacturer, Novo Nordisk, demonstrated in a study that people who received Wegovy lost an average of 12.4% of their initial body weight compared to individuals who received placebo. Another trial enrolled adults with type 2 diabetes, whose average age was 55, average body weight 220 pounds and average BMI 36. In this trial, individuals who received Wegovy lost 6.2% of their initial body weight compared to those who received placebo.
In trials of Zepbound, Eli Lilly measured weight reduction after 72 weeks in a total of 2,519 patients who received either 5mg, 10mg or 15mg of Zepbound once weekly and a total of 958 patients who received once-weekly placebo injections. In both trials, patients who received Zepbound at all three dose levels experienced a statistically significant reduction in body weight compared to those who received placebo.
In addition to weight loss, these drugs have been shown to offer other health benefits. For example, in November, Novo Nordisk reported that semaglutide 2.4mg (Wegovy) delivered a statistically significant 20% risk reduction in major adverse cardiovascular events (MACE) across age, gender, ethnicity and starting body mass index. The risk reductions in MACE were evident soon after initiation, suggesting an effect of semaglutide 2.4mg beyond weight loss alone, according to the data presented at the American Heart Association Scientific Sessions and published simultaneously in New England Journal of Medicine.
Primary care perspective
Family physicians have a unique perspective when talking to their patients about overweight, obesity and weight-loss drugs, says Dr. Smith. “We have cared for many of our patients since before 2008, which is how far back our EHR goes. We review their records and try to match their BMI to life events that might have occurred through the years.”
As patients get older, for example, they might not be exercising regularly or going to the gym or taking the walks they used to take. “We try to find out if their routine has changed in any way. Perhaps they are too busy taking care of young children to the point where they’re not paying attention to themselves. Was there a job change? Has their income level shifted? Have the kids left but now they must take care of their elderly mom or dad?
“We know Ozempic by itself won’t affect any of these stressors. So there are things that have to be addressed before we rely on semaglutide.”
Yellow light
All has not been smooth sailing for the blockbuster drugs. Given their popularity, availability has been spotty, says Dr. Smith. “Some pharmacies have it, others don’t.” Prior authorization has proven to be a hassle as well, she says. “We might have to demonstrate lifestyle changes, the existence of comorbid conditions, the fact that the patient is considering bariatric surgery, a one-on-one nutritionist consultation. And despite all that, the claim may still be denied. Or the patient may say, ‘I’ll pay the $600 out-of-pocket for a prescription,’ but lack the money to get refills. And we have had patients who were successful in losing a percentage of body weight but don’t make the necessary lifestyle changes. Wegovy isn’t set up for lifelong management of obesity.”
Due to negative side effects, a good proportion of people discontinue use of semaglutide, cancelling out its long-term effectiveness for weight loss. For example, Eli Lilly reports that Zepbound use may be associated with gastrointestinal adverse reactions, sometimes severe. The most commonly reported adverse events were nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection-site reactions, fatigue, hypersensitivity reactions, eructation, hair loss and gastroesophageal reflux disease. What’s more, birth control pills may lose their effectiveness for people on Zepbound.
Then there’s the cost.
Zepbound, whose active ingredient is tirzepatide, costs about 20% less than semaglutide, according to Eli Lilly, but still comes with a list price of $1,060 per month.
In July, pharmacy benefit manager Prime Therapeutics reported that among individuals who initiated GLP-1a drugs for weight loss, the total cost of care at a one-year follow-up came to $7,727 per person. Adherence to these drugs was also poor, with just 27% of individuals taking GLP-1a drugs after one year.
“GLP-1a drugs and their use for weight loss have taken the health care industry by storm, but several issues must be resolved, including how to ensure that those who may benefit most have access while maintaining overall pharmacy benefit affordability,” said David Lassen, PharmD, chief clinical officer at Prime, in a statement. “While we hope to see additional data to refine our guidance, health plans should consider programs to help adherence to avoid medication waste and comprehensive therapy plans – which include diet and exercise – to help people on their weight loss journey.”
What’s next?
Estimates of the percentage of the U.S. population who are overweight or obese range from 30% to 70%. Whatever the real number is, most healthcare providers believe it’s too high. Now, is there any way to put a positive spin on it? Can the weight-loss drugs help? Is the U.S. losing the battle against obesity?
“At least we have data on obesity today,” says Dr. Smith. “We have identified the problem, we have mapped it out. Now it’s a question of, how do we take that information and apply it to our individual patients who are at risk of obesity and other compromising conditions?
“It’s a sensitive topic, an emotional topic. What we can do is bring it home to our patients. We tell them, ‘Here’s the data. I am here to advise you, counsel you, be compassionate about this disorder that’s all around us, and help prevent you from being in the same state of suffering you see others experiencing.
“’Let’s work together in a compassionate and understanding manner. Let’s help you get through it.’”
Sidebar:
Bariatric surgery:
New anti-obesity drugs will not replace bariatric surgery. In fact, they may drive more surgical procedures, says Marina Kurian, M.D., president of the American Society for Metabolic and Bariatric Surgery. Repertoire asked Dr. Kurian about weight-loss drugs and bariatric surgery.
Repertoire: Analysts have predicted that sales of weight-loss medications such as Wegovy could reach $100 billion by 2030. One analyst predicted that by 2030, around 15 million adults in the U.S. will be treated with an anti-obesity medication. Do you expect that the popularity and reported effectiveness of semaglutide as a weight-loss tool will have an impact on bariatric surgery?
Marina Kurian, M.D.: We believe greater adoption of the new anti-obesity medications will lead to increasing demand for metabolic and bariatric surgery. Many patients may start with medications but then turn to surgery due to compliance or cost issues or for even more robust weight loss results and improvements or remission in diseases including diabetes, heart disease and sleep apnea. Metabolic/bariatric surgery has been shown to be the most effective and durable treatment for severe obesity yet least utilized treatment in medicine. About 1% of eligible patients undergo the surgery in any given year thus far. It’s also one of the safest operations in America, with a safety profile comparable to appendectomy, hip replacement and gallbladder surgery.
Studies show that:
- Bariatric surgery may reduce a patient’s risk of premature death by 30-50%.
- Patients may lose as much as 60% of excess weight six months after surgery, and 77% of excess weight as early as 12 months after surgery.
- On average, five years after surgery, patients maintain 50% of their excess weight loss.
- Most bariatric surgery patients with diabetes, dyslipidemia, hypertension, and obstructive sleep apnea experience remission of these obesity-related diseases.
The bottom line is, obesity is a disease that must be treated and cannot be ignored. Our hope is more people will seek the treatment for them without facing barriers.
Repertoire: The Centers for Disease Control and Prevention says that obesity prevalence was 42% from 2017 to 2020. Is there any way to look at this statistic in a positive way?
Dr. Kurian: Obesity is a serious disease, and it is not at all positive that it continues to increase. Obesity is linked to diabetes, heart disease, stroke, scores of other diseases and shorter lifespans. It would be a very positive development if we could decrease its prevalence, which in turn would lead to less other disease and people living longer, healthier lives.
Repertoire: Anything to add about treatment for people with obesity considering the popularity of Wegovy and Ozempic?
Dr. Kurian: Clearly, patients should seek advice from their own doctors. However, in general terms, neither drug therapy nor metabolic and bariatric surgery should be delayed until more severe disease occurs. Patients should not be forced to wait until their diabetes or obesity becomes worse or have a heart attack or stroke before they can have metabolic and bariatric surgery or other effective treatments.