Dec. 5, 2024 -- More than 1 in 8 Americans have taken Ozempic, the popular diabetes and weight loss drug. That makes it one of the most popular medications in history just seven years after hitting the market, with Ozempic and similar drugs the most popular class of medications by overall spending in the U.S. in 2023.
This surge in popularity has been relatively sudden, with the pandemic and celebrity influencers playing no small part in its marketing. In 2021, Ozempic wasn’t even on the top 20 list of best-selling drugs worldwide.
But by 2023, Ozempic reached third place on that list. And late last year, Nature forecast Ozempic would be the second most profitable drug in the world in 2024 with sales over $16 billion.
Semaglutide, the active ingredient in Ozempic, works by mimicking the hormone GLP-1, which is released in the small intestine after eating. This mechanism helps to control blood sugar, increase the secretion of insulin from the pancreas to help sugar enter cells, and regulate appetite. That GLP-1 mechanism led to its inclusion in a class that’s known as “GLP-1 drugs.”
Some analysts have forecast that GLP-1 drugs will change the world. More than half of the world’s population may be overweight or have obesity by 2035, and slowing this trend with weight loss drugs could have enormous impacts on public health.
But while Ozempic and similar blockbuster drugs offer promise, health experts note they carry significant downsides. For one thing, the drugs can have negative side effects, such as nausea, vomiting, and diarrhea. For another, people don’t continuously lose weight indefinitely, but instead usually hit a plateau, which can fall short of their weight loss goals.
Yet despite these concerns, sales of Ozempic and similar medications show no signs of slowing down, and the newer line of drugs promise even more weight loss than its predecessors, something those who have hit a plateau on current drugs could be excited about.
“What's really amazing is not that long ago, the ceiling for the percentage of weight loss with these drugs was around 10%, but now it's kind of the floor for these new medications,” said Jody Dushay, MD, assistant professor of medicine at Harvard Medical School and an endocrinologist at the Beth Israel Deaconess Medical Center in Boston.
How Does the Competition Fare?
A few promising new obesity drugs already on the market include the following:
Tirzepatide: A GLP-1 drug made by Eli Lilly and approved by the FDA for type 2 diabetes under the trade name Mounjaro and for obesity under the trade name Zepbound.
- In addition to stimulating the release of the hormone GLP, the drug also stimulates the release of a gut hormone called glucose-dependent insulinotropic polypeptide (GIP). GIP stimulates insulin secretion from the pancreas, which helps regulate blood glucose levels.
- In a large clinical analysis of U.S. adults who were overweight or had obesity and who started semaglutide or tirzepatide treatment, those receiving tirzepatide were more likely to achieve at least a 5%, 10%, and 15% weight loss at 3, 6, and 12 months, respectively.
- Data from the clinical trial showed Zepbound helped obese and overweight adults in the trial lose more weight and lose it faster than adults taking Ozempic or Wegovy.
Semaglutide (Rybelsus): An oral GLP-1 drug developed by Novo Nordisk containing the same active ingredient as Ozempic.
- FDA-approved for type 2 diabetes, it has not yet been approved for weight loss, meaning those with obesity may have trouble getting the drug covered by insurance.
- In a 68-week clinical trial involving 667 adults who were overweight or had obesity, those who took oral semaglutide lost an average of 15% of their body weight, compared to just 2.4% who were taking an inactive placebo — matching the weight loss achieved with Ozempic.
- Because it’s a peptide hormone, there’s a problem with absorption, necessitating the use of a high dose.
- Must be taken in the morning with 4 ounces of water and while fasting.
Some promising drugs in clinical trials that could be on the market within the next few years include the following:
Orforglipron: An oral GLP-1 drug developed by Eli Lilly.
- This is a non-peptide drug that can interact with receptors effectively and doesn’t have the absorption problems seen with Rybelsus. It can be taken at any time of the day and doesn’t require fasting.
- People with type 2 diabetes receiving the drug in a clinical trial achieved about a 10% weight loss in the first 26 weeks and about 14% weight loss in the first 36 weeks. This matches the weight loss achieved with oral semaglutide.
- The drug is in phase III clinical trials, with results expected in late 2025. If the results are positive, the drug could hit the market sometime in 2026.
CagriSema: A once-weekly injectable drug developed by Novo Nordisk that combines the active ingredients semaglutide, which is in Ozempic, and cagrilintide.
- Cagrilintide is a long-acting amylin analog. Amylin is a peptide hormone that helps reduce appetite and regulate blood glucose by promoting satiety (feeling full), slowing down gastric emptying, and inhibiting glucagon, another hormone that raises blood glucose levels.
- In phase II clinical trials, CagriSema showed an average weight loss of nearly 16%, with A1c reduction of a little over 2.2%. A1c tests measure the average amount of sugar in your blood over the past three months. An A1c level below 5.7% is normal, so a 2.2% reduction is significant.
- A unique property of the drug is that it doesn’t cause significant hypoglycemia, a condition in which your blood glucose level is lower than normal. Most GLP-1 drugs can lower blood glucose too much if taken with other drugs to lower blood sugar.
- Currently in a phase III study, the drug could be approved sometime in 2026 if results are positive.
Survodutide: A GLP-1/glucagon co-agonist developed by Boehringer Ingelheim.
- The drug combines the standard GLP-1 action of a drug like Ozempic with the hormone glucagon, which works to increase glucose production. This may improve weight loss while protecting against hyperglycemia.
- People receiving the drug in phase II trials achieved a weight loss of about 19% over 46 weeks.
- The FDA granted the drug a “breakthrough therapy” designation in September 2024 to treat non-cirrhotic metabolic dysfunction steatohepatitis (MASH), a chronic and progressive liver disease caused by a buildup of fat in the liver.
- The drug is in phase III studies, which are set to run through January 2026.
Retatrutide: Developed by Eli Lilly, it has shown great promise in clinical trials for significant weight reduction.
- The drug is a GLP-1/GIP/glucagon triple agonist. This means it works to activate GLP, GIP, and the hormone glucagon, which, taken together, seems to help those taking it achieve great weight loss and improved glucose levels compared to Ozempic.
- Participants with obesity in a phase II study lost up to 24.2% of their body weight over 48 weeks, compared to 2.1% for those taking a placebo. About 36%-48% of people lost more than 25% of their weight over 48 weeks. Some participants also experienced lower blood cholesterol levels and blood pressure, as well.
- Retatrutide is in a phase III trial to assess its safety and efficacy among different people who have obesity (who have sleep apnea, type 2 diabetes, and cardiovascular disease). Results are expected in early 2026.
“This is probably one of the most effective — together with CagriSema — of the medications that we are going to have. ... These will be the forerunners,” said Dimitris Papamargaritis, PhD, an expert on treatments for obesity and type 2 diabetes at the University of Leicester in the United Kingdom. “You may see even more than 20% weight loss over the estimated treatment difference compared to placebo,” he said.
“In the Retatrutide study, 100% of people lost at least 5% of their weight ... and many achieved weight loss going out to 25%,” Dushay said.
AZD5004: An oral GLP-1 drug revealed during ObesityWeek 2024 in early November 2024 and developed by AstraZeneca.
- Early findings from a study found that after four weeks of treatment in patients with type 2 diabetes, AZD5004 produced a 5.8% weight loss compared to placebo. This is in addition to a significant reduction in glucose and good tolerability of side effects.
Side Effects Remain a Problem
The most common negative side effects for the new, investigational drugs above are virtually the same as Ozempic. These can include nausea, diarrhea, dyspepsia, fatigue, constipation, acid reflux, upset stomach or stomach pain, low blood glucose, and injection site reactions for the non-oral formulations.
Most drugs in trials have about a 5%-15% dropout rate, and that number jumps up to about 20%-30% for the GLP-1/glucagon drugs — those GLP-1 drugs combined with the hormone glucagon.
“I would estimate 10 to 12 percent of people stop these drugs [due to side effects]. A much higher percentage have side effects that they tolerate,” Dushay said.
On the other hand, one beneficial side effect is that some people who lose a significant amount of weight from these drugs may find that they’re eligible for treatments not offered to overweight or obese patients.
“[The weight loss] is going to be associated with improvement of osteoarthritis ... or let patients meet the BMI threshold for getting a knee replacement ... IVF [in vitro fertilization] ... there are all these other conditions and procedures which have BMI [body mass index] cutoffs,” Dushay said. “With semaglutide we’re seeing direct effects on the cardiovascular system as well as on endothelial function. I think that’s really exciting.”
However, long-term data on the effect of weight loss drugs are lacking, experts say. People who undergo bariatric surgery for weight loss sometimes regain weight years later because the surgery can’t overcome lifestyle factors, such as poor diet and inactivity, that contribute to weight gain.
That same outcome — regaining a large of amount of weight previously lost — may happen with people who take weight loss drugs. It can be a nice bandage for a while, but after a year or two of taking the drug and then stopping, some people revert back to the same unhealthy behaviors.
Studies show this can certainly happen. In one study, which involved nearly 2,000 people who were overweight or had obesity, those who took semaglutide while altering their lifestyle were able to lose about 15% of their body weight after 68 weeks compared with a 2.4% loss for those who took a placebo. However, later in the trial a subset of people who stopped the drug still regained two-thirds of their previous weight before treatment.
Pharmaceuticals don’t necessarily solve the wider problem of obesity rates rising so sharply over the years worldwide, in part because of poor diets and inadequate exercise. What’s more, a drug that reduces calorie intake may also contribute to weak bones and muscles and possible nutritional deficiencies. Experts say more independent studies on these long-term effects are needed.
Lack of Access
Another problem: As new weight loss drugs come onto the market, they’re usually very expensive. Though highly effective for weight loss, Ozempic is only approved for type 2 diabetes, not obesity. This means insurance won’t cover the drug unless it’s specifically prescribed to treat that condition. This didn’t stop well-off celebrities and social media influencers from taking it, losing weight, and touting its benefits. Still, it could remain out of reach to the average person.
Semaglutide, the active ingredients in Ozempic, is approved by the FDA for obesity under the trade name Wegovy, which is a once-weekly injectable medication similar to Ozempic. Without insurance, Wegovy can cost as much as $1,300 per month. Whether or not your prescription of Wegovy, Ozempic, or even Zepbound is covered by insurance depends on your plan, and coverage can vary significantly between plans.
A 2024 study found that only 18% of company insurance plans with 200 or more employees cover GLP-1 drugs when prescribed for weight loss or other conditions. And among those companies, only 28% with 5,000 or more workers offer benefits that cover GLP-1 drugs for weight loss alone.
Unless they’re prescribed for heart attack or stroke, Medicare doesn’t cover current weight loss medications at all. That will hold true for any of brand-new weight loss drugs coming to market that may be more effective than Ozempic, Wegovy, or Zepbound.
“If you have Medicare, you can't get any of these newer drugs,” Dushay said.
Medicaid coverage varies by state. Some states prefer one drug over another, and Medicaid may only cover a drug if you are diagnosed with diabetes or are a certain age.
This leaves the average consumer in the hole for $1,000 or more if the drug is prescribed off-label to manage their weight. And a wider variety of available drugs in the coming years will likely not lead to lower prices.
“I’m not optimistic that prices will come down,” said Dushay. “They’re all going to be on patent for a while ... and if you modify the mechanism of administration, you get to be out of patent longer. ... I don’t think a major motivator to research these medications is lowering the cost.”
