Read Part 1 of the story here.
Recently, we learned about the science behind the semaglutide, the active ingredient in the diabetes drug Ozempic and its sister weight-loss drug, Wegovy. But what's the actual difference? Or is there one? And how do you parse the whirlwind of information (and misinformation) if you are hankering to visit the seemingly magical land of Oz-empic, where pounds melt away like the Wicked Witch of the West? Our Stanford Medicine experts are here to help answer those questions and more.
Ozempic versus Wegovy versus up-and-coming Mounjaro
Ozempic was approved by the Food and Drug Administration in 2017 as a treatment for Type 2 diabetes. In 2021, the FDA approved another medication, Wegovy, to facilitate weight loss in people with obesity or those who were overweight and have at least one weight-associated condition (think high cholesterol or high blood pressure). Both Wegovy and Ozempic contain semaglutide, but in slightly different doses. The drugs are injected weekly under the skin of the upper arm, abdomen or thigh, and they're not cheap: A monthly supply of either drug hovers around $1,000 if not covered by insurance.
As an approved diabetes treatment, Ozempic is often covered by health insurance when it is prescribed for people with the condition. In contrast, Wegovy is often not covered, to the consternation of many obesity medicine specialists.
"Weight loss drugs in general are often not covered by private insurance," said Sun Kim, MD, associate professor of endocrinology and member of the Stanford Diabetes Research Center. "People without diabetes have been trying alternative ways to get these drugs."
It's possible to order semaglutide injections online, usually through a telehealth visit with a doctor, and some doctors prescribe Ozempic off-label (meaning for a purpose -- weight loss -- other than for which it was approved) to people desperate to lose weight. "Last winter there was a huge shortage of Ozempic, and many of the phone calls to our clinic were from people with diabetes who were having trouble accessing it," Kim said.
In 2022, another drug, Mounjaro, was approved by the FDA for the treatment of Type 2 diabetes. The active ingredient in Mounjaro is a drug called tirzepatide, which targets both the GLP-1 receptors and the receptor for a similar hormone, GIP. "This is the first drug that targets both gut hormones," Kim said, "and it will be very popular."
We know these drugs work, but is it ethical to use them strictly for weight loss? The answer is surprisingly unclear, in part because obesity is often considered to be a kind of moral failing rather than a disease. That view is wrong, said Dan Azagury, MD, associate professor of surgery and medical director of the Stanford Lifestyle and Weight Management Clinic.
"Obesity is very stigmatized," he said. "I treat people who have been struggling with obesity their entire lives -- they've tried everything. It can be a life-threatening condition. The idea that these drugs should be saved for people with diabetes implies that there is some kind of hierarchy of disease, and that people with obesity should just close the refrigerator. I've never had a patient say 'What's this diet thing? I've never tried that before.'"
Kim doesn't have a problem with people using these drugs for weight loss, either. "Losing weight is challenging for all of us but beneficial for most people with weight-related co-morbidities. I do think that, in times of shortage, people with diabetes should be prioritized."
The dark side of semaglutide
The FDA estimates that about 70% of Americans have obesity or are overweight and are at risk of serious health complications including heart disease, stroke and diabetes. As Kim said, losing weight is a winning proposition for many of us. But despite people's desires for a quick, easy fix, these medications are intended to be used indefinitely.
"We have to think of obesity as a chronic disease," Kim said. "Someone with high blood pressure doesn't expect to stop taking blood pressure medications once normal blood pressure has been achieved. If you stop taking semaglutide, you generally regain the weight back."
"Regardless of the obesity intervention, we don't want our patients to yo-yo on their weight," said obesity medicine specialist Shebani Sethi, MD, clinical assistant professor of psychiatry and behavioral sciences. "There are negative consequences, both psychological and physiological from repeatedly losing and regaining significant amounts of weight."
Not all pounds are created equal, either.
Sethi, who is the director of the Metabolic Psychiatry Clinic, said that the impact on a person's lean mass, or muscle, can be significant. "Ideally, we want most weight loss to be fat mass alone, and some lean mass muscle loss is common in weight loss interventions, however, in a sub-analysis from a clinical trial, as much as 39% of the weight lost on semaglutide was lean mass, a much higher percent of lean mass loss, compared to most other weight loss techniques. Therefore, we advise a resistance training program when starting these medications. And then if one goes off the medications, the weight you regain is not going to be muscle, it will be fat (increasing the risk of something called sarcopenic obesity, in which an individual has decreased muscle mass and increased fat tissue). So, you have loss of muscle mass, strength and function, which can be especially worrisome in the elderly."
The medications also have side effects, including nausea, vomiting, diarrhea, constipation and abdominal pain. And their long-term safety for people with a family history of pancreatic cancer or pancreatitis (insulin is made in the pancreas) is not clear.
Even without these downsides, however, the out-of-pocket cost is prohibitive for most people unfamiliar with the red carpet.
"There is still a huge problem with access for people with obesity," said Azagury. "Bariatric surgery has been around for decades, but we still operate on only about 1% of people who would qualify for the procedure even though the health benefits are very clear. Now we have a non-surgical option that is a real game-changer. It is changing the way we can provide care for these people, and we need to lower the barrier for people to access this care. We need insurance coverage for weight loss drugs."
But here's where the rubber meets the road: Despite decades of evidence that lugging around fewer pounds is a net win for people and insurers, a recent study calculated that if Medicare covered the cost of Wegovy for only 10% of the 42% of people in the United States over 60 who are estimated to have obesity, it would cost the insurer nearly $27 billion per year -- nearly 20% of its total budget. (Notably, that number doesn't take into account the money Medicare would likely save on obesity-related health care as the country's collective pounds vanish.)
What's the skinny?
It's clear we're looking at a new frontier in weight-loss medications, which can give surgical weight-loss treatments a run for their money in terms of percent of body weight lost. But they can come with significant drawbacks for your muscle mass and your pocketbook. They also don't address the causes of overeating that plague many people.
"These drugs aren't a cure for emotional or stress eating," said Sethi. "The psychological stress behind these behaviors doesn't necessarily go away. But some amount of weight loss can jump-start other ways for people to improve their health."
Whether you choose diet, exercise, counseling, medication or surgery (or a combination!) expert advice can help you get to your goal safely.
"It is important to treat the disease as a whole," Azagury said. "At the clinic, we screen people for eating disorders, discuss levels of physical activity and talk about treatment options with them. Having multiple tools to address weight loss is not a luxury; it's a necessity."
Finally, it's possible to be both realistic and cautiously optimistic.
"These medications alone are not a cure for obesity in this country," Sethi said. "People body shame and fat shame too much in our society. But particularly for people with severe obesity, these medications can give them momentum to make lasting, long-term changes. It can give them hope."
Photo by Cozine