Thanks to decades of research, we now know that diet, exercise and other lifestyle modifications are essential for general wellness but don’t move the needle much when it comes to managing obesity. And now that we are recognizing obesity as a disease, treating it with pharmaceuticals is gaining acceptance. The rise in popularity of newer anti-obesity medications (AOMs) such as semaglutide (Ozempic, Wegovy) has demonstrated their power—people with obesity can lose more than 20% of their body weight with these drugs, resulting in major health benefits.

Research shows that Wegovy reduces risk for heart attack, stroke and cardiovascular death by 20% in heart disease patients who are overweight or have obesity. Over the next decade, the drug’s widespread use could prevent up to
1.5 million heart attacks and strokes and 43 million cases of obesity.

Bottom Line asked Angela Fitch, MD, FACP, FOMA, president of the Obesity Medicine Association and chief medical officer of the health-care company knownwell, to explain how these drugs work…

Semaglutide (Ozempic, Wegovy): The hot new obesity drug is neither new nor designed as a weight-loss drug. Semaglutide branded as Ozempic was FDA-approved as a treatment for type-2 diabetes in 2017, thanks to its ability to boost insulin secretion and keep blood sugar levels stable. In 2021, the same drug, rebranded as Wegovy and at a slightly higher dose, was FDA-approved for people who have obesity or who are overweight and have health problems related to their excess weight.

Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, a medication that mimics the naturally occurring gut hormone GLP-1 that makes people feel full after eating. Like the synthetic thyroid hormone taken by people with hypothyroidism, semaglutide provides GLP-1, reducing the drive to eat while triggering insulin release to combat or help reverse diabetes. Semaglutide also slows the rate at which the food you do eat passes through the stomach into the small intestine.

Result: Almost 40% of people taking semaglutide lose 20% or more of their body weight. By comparison, only 5% of people lose 20% or more of their weight using diet and exercise alone.

How it is taken: Weekly self-­injections under the skin of the upper arm, abdomen or thigh.

Common side effects: Nausea is quite common. Diarrhea, vomiting, constipation and stomach pain also can occur, as can low blood sugar levels in people with diabetes who are taking other medications to manage their blood sugar.

On the horizon: Oral semaglutide, in a class of drugs called oral GLP-1 receptor agonists, now is available as a diabetes treatment under the brand name Rybelsus, but it is expected to be approved for weight loss at a higher dose and under a different name. Taken daily on an empty stomach, you must wait at least 30 minutes to eat, drink or take any other oral drugs. You can swallow the pill with only a few sips of water—no more than four ounces.

Tirzepatide (Mounjaro) is another GLP-1 receptor agonist to treat diabetes. But unlike semaglutide, it includes the hormone glucose-dependent insulinotropic polypeptide (GIP, formerly known as gastric inhibitory peptide) that further dampens appetite. On the fast-track to be approved as an AOM, Mounjaro will hit the market this year.

Result: 60% of people taking tirzepatide lose 20% or more weight.

How it is taken: Weekly self-injections.

Common side effects: Nausea, diarrhea, vomiting, constipation, stomach pain.

On the Horizon

Retatrutide. In trials, 80% of people with obesity lost 20% of their body weight on retatrutide, a number previously unheard of with AOMs. Retatrutide adds a third agonist—a glucagon agonist—along with a GLP-1 agonist and GIP agonist, earning it the nickname “Triple G.” (Glucagon is a pancreatic hormone that regulates blood sugar levels.)

Bonus: Retatrutide is effective at helping people with obesity and non-alcoholic fatty liver disease (NAFLD), an often-silent condition affecting 10% to 20% of Americans. Being overweight or having high blood pressure, type-2 diabetes, prediabetes or high cholesterol can cause fat to accumulate in the liver, which can lead to cirrhosis, permanent scarring and hardening of the liver. Retatrutide reverses NAFLD in 90% of patients. It will be several years before this injectable receives FDA approval.

Orforglipron and danuglipron. These AOMs are in a class of drugs called oral small-molecule GLP-1 receptor agonists. Unlike oral semaglutide, you needn’t wait 30 minutes to eat after swallowing orforglipron or ­danuglipron. They also don’t require refrigeration during transit (Ozempic and Wegovy do), making them easier and less expensive to mass produce.

Frequently Asked Questions

Who can take AOMs? The best candidates have a body mass index (BMI) of 30 or greater…or a BMI of 27 or greater plus at least one weight-related health complication such as high blood pressure, type-2 diabetes or sleep apnea.

Will I need to take the drugs forever? AOMs must be taken indefinitely. In theory, some individuals may be able to take temporary breaks, holding weight gain at bay with large amounts of exercise and dietary diligence, but as the weight creeps back up, medication would need to be resumed. Your doctor will want to see you every four to six weeks for the first six to nine months to conduct blood work to assess your cholesterol levels, kidney issues, thyroid function and diabetes status. If your AOM dulls your appetite so significantly that you’re not getting sufficient nutrients, you may need to take a multivitamin. Once your weight loss stabilizes, you can have annual or ­biannual check-ups.

Will insurance cover the cost of the drugs? With a diabetes diagnosis, insurance (including Medicare) will cover most GLP-1 receptor agonists. But coverage is trickier if you don’t have diabetes. Between 30% and 50% of employers offer coverage for medications to treat obesity. The bipartisan Treat and Reduce Obesity Act, before Congress for over a decade, aims to guarantee AOM coverage, but until that act passes, most people will need to pay out of pocket—typically more than $1,000 per month.

What about the scarier-sounding side effects? There are a few that you may have heard about…

Ozempic face and Ozempic butt—the wrinkling, gauntness and sagginess sometimes seen in the faces or glutes of people who’ve quickly lost substantial weight. These occur as the skin struggles to keep pace with a changing body.

Stomach paralysis. A few cases of AOM-related gastroparesis and intestinal blockages have made headlines. Patients who experience vomiting of undigested food that was eaten several hours earlier, severe constipation, abdominal pain, nausea and heartburn should speak with their doctors—this probably isn’t the right drug for them.

Cancer risks. AOMs carry a black box warning for medullary thyroid cancer, but this risk has been observed only in animal studies. If you have a personal or family history of medullary thyroid ­cancer/multiple endocrine neoplasia type II, GLP-1 receptor agonist medications are not recommended.

Surgical complications. Slowing transit time through the gastrointestinal tract means food remains in the stomach longer. When under anesthesia, this can cause the food to enter the lungs. If you are planning to have a surgical procedure, tell your doctor and anesthesiology team that you are taking an AOM.

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