The approval by the U.S. Food and Drug Administration (FDA) of the weight loss drug Zepbound (tirzepatide) will give millions of Americans with overweight and obesity a powerful new option for shedding excess pounds.
Zepbound, a once-weekly injected medicine with the same active ingredient as the popular type 2 diabetes drug Mounjaro, was cleared by the FDA for chronic weight management by adults with obesity, and by adults with overweight plus at least one weight-related health issue such as high blood pressure, type 2 diabetes, or elevated cholesterol.
Tirzepatide, the active ingredient in Zepbound and Mounjaro, is the first drug in a new family of medicines that target two hormones — glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) — that are involved in maintaining healthy blood sugar levels and sending signals of satiety from the gut to the brain.
By contrast, the type 2 diabetes drug Ozempic and the weight loss drug Wegovy both contain a different active ingredient, semaglutide, that targets only the hormone GLP-1.
Semaglutide has been available longer, and was considered among the most powerful options for medication-aided weight loss until tirzepatide hit the market, says Fatima Cody Stanford, MD, MPH, an obesity medicine physician, scientist, educator, and policymaker at Massachusetts General Hospital and Harvard Medical School in Boston.
“When semaglutide came out it was the highest weight loss we had ever seen with a drug — that is, until we saw the results for tirzepatide,” Dr. Stanford says.
Clinical trials highlight the dramatic weight loss results for semaglutide, as well as the even more substantial weight loss results for tirzepatide.
A landmark study published in 2021 in the New England Journal of Medicine found that weekly semaglutide shots helped people with overweight and obesity lose an average of 15 percent of their body weight over 68 weeks.
Another pivotal study, published in 2022 in the New England Journal of Medicine, found that tirzepatide helped people with overweight or obesity lose an average of 21 percent of their body weight over 72 weeks when they didn’t make any lifestyle changes.
Just last month, a study published in Nature Medicine found that tirzepatide helped people with obesity lose an average of 27 percent of their body weight over the same time frame when combined with lifestyle changes.
“When we saw the results for tirzepatide it was the first time we crossed that 20 percent threshold for average total body weight loss,” Stanford says. “Right now, if we look at every medicine that has ever come out, this is by far the most potent one that has ever been approved by the FDA.”
Read on for more of Stanford’s insights on Zepbound, including more details on how it works, how it compares with its rival weight loss medication Wegovy, and whether people using it can expect to experience side effects.
Everyday Health: How effective is Zepbound for weight loss, and how does it work?
Fatima Cody Stanford: It acts on two hormones in the body, GLP-1 and GIP. The GLP-1 portion works on influencing a portion of your brain that tells you to eat less and store less fat. The reason it’s so potent is that it upregulates the portion of your brain that tells you to eat less and downregulates the portion of your brain that tells you to eat more. Then GIP works on improving how storage of fat happens so your body doesn’t want to store as much fat.
EH: How does Zepbound compare to Wegovy? Are there some patients who might be a better fit for one of these drugs over the other?
FCS: I think a lot of the choice may have to do with what’s covered by insurance. It will also come down to what the patient needs in terms of weight loss. If the patient needs a higher degree of weight loss or a higher degree of improvement in blood sugar then they may need Zepbound. If they don’t need something as strong, then they may take Wegovy instead.
EH: Drugmaker Eli Lilly has said Zepbound will cost more than $1,000 a month, with discounts reducing the out-of-pocket price based on what type of insurance coverage people have. What do we know at this point about how much Zepbound will actually cost patients or whether insurance will cover it?
FCS: It’s an expensive drug. Many people will pay I think between $500 and $1,000 even with insurance if their plan doesn’t cover the drug. And if they try a discount program like GoodRx it might get down to $450 or so, but that’s still very pricey. Some people who have excellent private health insurance that covers the drug will likely pay about $30 for Zepbound.
EH: Do you anticipate shortages for Zepbound like we’ve seen with Wegovy?
FCS: I do anticipate shortages. I’m going based on what we went through with Wegovy. Right now, starting a new patient on Wegovy is impossible because the lower starter doses that people need to take in the beginning of treatment are not available. With these injected medicines you can’t just cut it in half like you can with a pill when you need to gradually increase the dose a patient takes and the exact dose you need isn’t available. So I would expect shortages.
EH: What do we know about side effects for Zepbound, and how these compare to Wegovy?
FCS: Overall the safety of these drugs is very similar. What’s interesting is that so far I’m not seeing as many issues with common side effects with tirzepatide. In fact, I’ve had some patients who didn’t tolerate semaglutide because the nausea was too intense or they didn’t tolerate abdominal pain or constipation — they switched to tirzepatide and were able to tolerate it. Overall the safety of these drugs is very similar.
EH: Can people be on Zepbound for life?
FCS: Yes. That’s a one-word answer!
EH: Can Zepbound be combined with other weight loss medicine?
FCS: You can absolutely combine this with other medicines as long as they’re a different category of medicine that works in a different way. I have many patients who take other drugs like metformin or phentermine for weight loss in addition to tirzepatide. Most clinicians may not have the knowledge to do this. When I look in my own clinic at my patients who are the highest responders in terms of weight loss, it’s not one agent, it’s several. I have one patient I’ve been seeing for 11 years and who has been with our clinic for 15 years, and she has lost 60.7 percent of her total weight. She did weight loss surgery, and has been on several different medications in addition to surgery to get to that amount of weight loss over a 15-year period.
EH: Do you think drugs like Zepbound will make weight loss surgery obsolete?
FCS: No. The winners are really the patients who have surgery and then who are also on a GLP-1 drug like tirzepatide or semaglutide and other things, too. These are the people who are getting to 50 percent or more in total body weight lost.
EH: One criticism with the clinical trials for older weight loss drugs is that most of the participants were white. Has there been more diversity with newer medicines like Zepbound?
FCS: It’s a problem, definitely. In my clinic, around 40 percent of my patients are Black, and so far we haven’t seen a difference in response to GLP-1 drugs in terms of weight loss. We’re seeing really great overall outcomes for these patients. I would say that compared with five years ago, companies that are testing new drugs now are doing a better job with recruiting diverse participants in trials.
EH: What else should patients know about Zepbound?
FCS: The key thing is I just want people to be mindful that the medications are definitely a tool that I will continue to use. But they are just one tool. They are not by themselves going to solve our obesity problem.
