Medically reviewed by Elizabeth Gomez, MSN, FNP-BC
For most of our lives, there has been no good weight loss drug. While the U.S. Food and Drug Administration has approved a small number of pharmaceuticals for weight loss, each has had critical drawbacks, such as moderate effectiveness, bad side effects, or a limit on how long they may be taken. Over the decades, a number of weight-loss drugs have been pulled off the market because they were eventually shown to have significant negative long-term health effects.
Bariatric surgery can work wonders, but it’s expensive and incredibly invasive, and most people don’t think of it as a viable option. That means that the vast majority of us are stuck with diet and exercise, and the cruel fact that weight loss remains incredibly hard and weight loss maintenance even harder.
Wouldn’t it be amazing if there were a drug that could help?
It may finally be true. For the first time in living memory, experts now believe that new medications can completely revolutionize the medical treatment of weight loss.
The landscape first changed in 2021, when the FDA approved Wegovy, perhaps the most promising weight-loss drug yet invented. Wegovy is a semaglutide, also known as a glucagon-like peptide-1 (GLP-1) receptor agonist. It was designed as a type 2 diabetes drug and is still used as a diabetes drug. You may know it (or take it) as Ozempic or Rybelsus.
Experts believe that Wegovy will bring monumental change to obesity treatment, but the news in late March was even more thundering: Another diabetes drug, tirzepatide (Mounjaro), showed even better results in a major trial.
This article will explore these two diabetes drugs and how they may change obesity treatment for good.
Semaglutides work for patients with type 2 diabetes by mimicking the effects of the hormone GLP-1, which is usually released by the intestine during meals. GLP-1 does a variety of things: It tells the liver to release less glucose, it slows digestion, and it provokes the feeling of fullness or satiety. Put it all together, and when patients with diabetes take the drug it reduces blood glucose levels while also helping them eat less.
Ever since semaglutides were first studied, researchers have known that they can help confer some weight loss. Scientists from Novo Nordisk further learned that by tweaking the chemistry and the dosage, these medicines could actually provoke an unprecedented amount of weight loss. In its most important trial, Wegovy was found to help obese adults lose an average of 15% of their body weight — about 34 pounds on average.
The study participants also enjoyed health benefits across the board, including improvements in blood pressure and A1C. Most tolerated the drug well. Just 4.5% of the patients stopped taking Wegovy due to gastrointestinal side effects.
This magnitude of these weight loss and cardiometabolic benefits, from a drug that carried only a minimum of side effects, was basically unheard of.
Stephan Guyenet, a neuroscientist that has worked extensively on the brain’s relationship to nutrition and eating behavior, offers an explanation for why semaglutide is so effective. Although it primarily affects the metabolic system, Wegovy and related drugs also act directly on the parts of the brain that regulate food intake. Patients feel full faster while eating and are less susceptible to food cravings between meals.
Semaglutide’s remarkable effects go beyond reduced food intake. As many dieters have intuited, and as the science shows, weight loss often results only in increased hunger and slowed metabolism. The body seems to fight to get back to its former weight. Semaglutide somehow appears to chemically lower the brain’s fatness “setpoint.” Your brain stops monkeying with your hunger and metabolism, and allows you to lose weight and keep it off.
Wegovy is actually the second drug of its class to be approved for weight loss. The first is liraglutide (Saxenda), and it is also a successful type 2 diabetes drug under a different name, Victoza. Saxenda also confers effortless, lasting weight loss, but only about half as much as Wegovy, not quite enough to be considered a true game changer.
Wegovy is extremely expensive and is likely to remain so for the foreseeable future. At the time of writing, GoodRx, an online resource for comparing prescription prices, reports a minimum price of about $1,350 in my corner of the USA, and that’s with a coupon. Given that Wegovy needs to be taken indefinitely — patients that stop the treatment can expect to gain their weight back — the lifetime cost would be staggering.
Nevertheless, Novo Nordisk has been overwhelmed with demand, to the point that it has temporarily put the brakes on advertising its new miracle drug.
Initial indications are that insurance companies are more willing to reimburse for Wegovy than they have been with the prior generation of less-effective weight loss pharmaceuticals. But it remains to be seen how accessible the drug will be and how widely it gets adopted.
As always, prices may be drastically lower in other countries — when Wegovy gets there, that is. At the moment, it seems to be available only in the United States, and it would hardly be surprising to see Novo Nordisk concentrate on maximizing the more lucrative American market before expanding.
Wegovy may be the game changer, but there’s another new drug on the horizon that may be even better.
That drug is tirzepatide, and it was also originally developed to treat diabetes. Tirzepatide has the same effect as Wegovy and other semaglutides — it mimics the function of GLP-1 — but it additionally mimics another hormone, gastric inhibitory polypeptide (GIP). The combination appears to be even more effective.
[Update: Just a few days after this article was originally published, the FDA announced that it had approved tirzepatide as a diabetes treatment. The drug will be re-named Mounjaro. It has not yet been approved specifically as a weight loss remedy. If and when it is, it may be marketed under a second, different name.]
At the end of April, pharmaceutical giant Lilly released jaw-dropping new evidence on tirzepatide’s effectiveness. In a phase 3 trial, the final and most significant hurdle for new therapies, the highest dosage of the experimental drug caused overweight or obese participants to lose 22.5% of their body weight, for an average loss of 52 pounds per person, all within a mere 72 weeks.
That’s about 50% more weight loss than Wegovy and on par with the extraordinary results that are associated with bariatric surgery. Lower doses delivered less weight loss, but the results were still impressive.
The side effects may be slightly more intense on tirzepatide — up to 33% of participants experienced some nausea, and on the higher doses 6–7% had to stop taking the drug due to such issues — but it’s easy to guess that most people would gladly put up with a little belly distress in order to lose 50 pounds.
In earlier trials, as detailed by our friends at DiaTribe, tirzepatide was found to have significant diabetes benefits for a variety of different populations, including patients both on and off insulin therapy. These trials resulted in huge decreases in A1C. And at the recent ATTD conference in Barcelona, a series of experts explained how tirzepatide has been found to amazingly boost insulin sensitivity, reduce liver fat, and improve glycemic control. Some of these results were almost too good to believe:
In one case, a 61-year-old individual had obesity and type 2 diabetes, was taking metformin, had an A1C of 10.1%, and a TITR (time in tighter range, or percent of time spent between 70 and 140 mg/dL) of less than 1% each day. After 52 weeks of taking a 15 milligram (mg) dose of tirzepatide, the subject’s TITR skyrocketed to over 98%, A1C fell by more than 5 percentage points, and they experienced a weight loss of around 50 pounds.
We can expect tirzepatide to be at least as expensive as Wegovy, and perhaps even more so. As a result, there’s no telling when tirzepatide will be available and whether most insurance companies will be willing to pay for it. And like Wegovy, it will likely need to be taken indefinitely in order to enjoy its benefits long term.
Given the astounding weight loss and metabolic improvements that these drugs confer, it is highly likely that they’ll also eventually be shown to reduce cardiovascular disease and long-term diabetic complications. But it’s possible that insurance companies will be hesitant to pay the very high prices before that link is firmly established.
Major studies of both Wegovy and tirzepatide show that these two drugs can trigger an almost unbelievable amount of effortless weight loss, approaching or equaling that found in bariatric surgery. They also result in major improvements to markers of diabetes management.
Wegovy is available today in the United States, but demand has been so overwhelming that its maker has had to intentionally slow down its rollout. Tirzepatide, marketed under the name Mounjaro, has been approved for use in diabetes so recently that we don’t know how available it will be for customers that can afford it. It is not yet indicated for non-diabetic patients.
These two drugs, simply put, could revolutionize obesity treatment and type 2 diabetes care. But, in each case, it remains to be seen to what extent insurance companies will be willing to pay for them, and if or when they’ll be widely accessible for patients in the United States and elsewhere.