Ozempic / Wegovy and Mounjaro / Zepbound (and their base components semaglutide and tirzepatide) are currently the “hottest” medications on the market. You don’t have to be a doctor or pharmacist to get to this conclusion; the stock market tells the story. Sales of Ozempic / Wegovy (based on semaglutide) from Novo Nordisk and Mounjaro / Zepbound(based on tirzepatide) from Eli Lilly and Company have exploded thanks to Americans’ weight-loss craze. Investors are pouring their money into the two leading manufacturers that developed these medications because everything points towards even more growth over the next few years.
To illustrate, compared to an increase of 42% in the S&P 500 market index from the end of February 2023 to the end of August 2024, Eli Lilly’s share price almost tripled, and Novo Nordisk went up 175%. There are a few reasons for the exceptional growth in Novo Nordisk and Eli Lilly’s share prices and a good reason why Eli Lilly is outperforming Novo Nordisk so markedly.
To understand what’s going on, it’s essential to know how these treatments gained so much popularity so quickly. The following few sections will summarize the histories of Ozempic and Mounjaro.
How did Ozempic gain its reputation?
Ozempic (generic name: semaglutide) was first marketed as a drug for managing diabetes in adults living with type 2 diabetes who were not responding adequately to controlled diets and for whom the primary medication (Metformin) wasn’t working.
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA). GLP-1 is a hormone produced in the gut. It is released in response to food, prompting the release of insulin from the pancreas and blocking the release of glucagon. Insulin’s job is to keep blood glucose from rising too high after eating. Glucagon keeps blood glucose levels from dropping too low. It stimulates the conversion of glycogen stored in the liver to glucose, which can be released into the bloodstream. When blood glucose levels fall too low, the pancreas releases more glucagon. The two hormones work together to stabilize blood glucose levels.
In people with type 2 diabetes, GLP-1 slows digestion and stimulates increased natural insulin production. This means that Ozempic does not act like other treatments for diabetes, such as insulin injections or oral insulin, which are external sources.
Ozempic was first released in 2017 and quickly became popular because it was easier to manage for most patients. Compared to daily doses of insulin or Metformin, it required just one weekly injection from a single dosing pen, suitable for a whole month. People with diabetes who forget to take their scheduled medication could be at severe risk of hyperglycemia. Hence, a more straightforward schedule for administering the vital medicines was a big plus.
How did Mounjaro gain its reputation?
Mounjaro (generic name tirzepatide) was released in 2021. It combines the same GLP-1RA in semaglutide with a glucose-dependent insulinotropic polypeptide (GIP). Have another look at the top left corner of the diagram above describing how these glucose levels are controlled. GLP-1 and GIP are two incretins that increase the release of insulin. The formulation of tirzepatide provides both GLP-1 and GIP, acting as a backup mechanism in case one doesn’t work adequately and boosting each molecule’s total efficiency. It’s garnered the term “twincretin,” the trials showing that it provides better A1C benefits than pure GLP-1 without adding any gastrointestinal side effects.
Initially, Mounjaro was going head-to-head against Ozempic. The two drugs are similar in that they are both taken as weekly injections, giving them the same profile in terms of the benefit they represent over daily medication. In all probability, once Mounjaro reached the market, the main selling points that pushed its popularity were the growing shortage of Ozempic on the shelves in pharmacies and the marginally better comparative results that came out of the SURPASS-2 trials which tested Mounjaro against semaglutide directly.
In SURPASS-2, between 82% and 86% of participants given tirzepatide had achieved an HbA1c level below 7.0%, compared to 79% of those given semaglutide. It is not a dramatic improvement, but it is enough to sway doctors to begin prescribing Mounjaro.
How did diabetes medications Mounjaro and Ozempic morph into Zepbound and Wegovy as weight loss treatments?
What makes diabetes drugs so unique when it comes to weight loss?
It started with Ozempic back in 2019. As feedback from clinical trials was being analyzed, many of the people with diabetes enrolled in the trials were reporting an unexpected and very welcome side effect. They were losing substantial amounts of weight, and the more overweight they were, the more they were losing. This led Novo Nordisk to sponsor a full round of testing of Ozempic (STEP 1 trials), examining its ability to induce weight loss.
The conclusions drawn from STEP 1 were that for overweight or obese adults, a weekly subcutaneous injection of semaglutide plus moderate diet and exercise was likely to produce substantial, sustained, and clinically relevant weight loss. Novo Nordisk extended the STEP trials and, with the results coming out of STEP 5, took the steps necessary to get FDA approval for Wegovy, which has a maximum strength of 2.4 mg compared to 1 mg for Ozempic.
To say that the publication of these trial results caused a wave of interest among consumers is an understatement. Within weeks, social media platforms were awash with posts from people who were overjoyed by the results of using Ozempic for weight loss. In some cases, leading personalities in the entertainment and information sectors climbed onto the bandwagon to publicize their own experiences with Ozempic, and shelves of pharmacies all over the country were swept clean. It even got to the point where people who had been taking Ozempic for their diabetes for several years were unable to get their prescriptions filled because the production of the drug couldn’t keep up with demand.
And then along came Mounjaro!
The management at Eli Lilly and Company was well aware of the dramatic impact of semaglutide in this new sector of weight control. So immediately after FDA approval of Mounjaro as a treatment for diabetes in 2021, the company began its own series of tests to see how Mounjaro stacked up as a weight-loss drug.
In SURPASS-2 trials, tirzepatide in three different strengths was tested against weekly injections of semaglutide, which is only available in Ozempic in a 1.0 mg dose. Reductions in body weight with tirzepatide were dose-dependent, as shown in the table:
Weight loss |
||
| Semaglutide 1.0 mg | ||
| Mounjaro 5 mg | 16.7 lb (7.6 kg) | 12.6 lb (5.7 kg) |
| Mounjaro 10 mg | 20.5 lb (9.3 kg) | |
| Mounjaro 15 mg | 24.7 lb (11.2 kg) | |
At all doses, tirzepatide was superior to semaglutide.
Why must Ozempic and Mounjaro be prescribed “off-label” for losing weight?
Until very recently, the FDA only approved both of these diabetes medications as treatments for people with type 2 diabetes. Doctors can use their judgment to prescribe either for weight loss, as we have described more fully. However, this affects the cost to consumers because most insurance companies do not reimburse patients for off-label drugs they purchase.
Novo Nordisk and Eli Lilly and Company have taken quite different routes to get their respective products into customers’ hands as registered weight-loss solutions.
How can you get semaglutide as a prescribed weight-loss medication?
Novo Nordisk brought a higher-dose version of Ozempic onto the market in 2022 with the brand name Wegovy. Wegovy delivers 2.4 mg of semaglutide in a weekly injection. The STEP 5 Trial was launched in 2018, with the final report being published in March 2021. The study’s purpose was to establish whether, and on average, how much weight was gained or lost over thirty months by subjects receiving the semaglutide. Participants were adults who were clinically obese (with a body mass index of 30 or higher) or overweight (BMI between 27 and 30 with at least one weight-related comorbidity) and with a history of at least one self-reported unsuccessful dietary effort to lose weight.
From early October 2018 to February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (152 participants) or placebo (152 participants.) All subjects were instructed to follow the same routines of a healthy diet and physical exercise, and it was a double-anonymized study, meaning that neither the supervising medical staff nor the participants knew whether it was a placebo or a drug.
The results speak for themselves:
| Control group (injecting placebo) | Semaglutide(injecting 2.4 mg) | |
| Number of participants at the start = 304 | 50% | 50% |
| Percentage of subjects who lost at least 10% of body mass | 1.3% | 61.8% |
| Percentage of subjects who lost at least 15% of body mass | 7.0% | 52.1% |
| Percentage of subjects who lost 20% or more of body mass | 2.3% | 36.6% |
| Average reduction in waistline | -0.6% | -16.7% |
| Average weight loss | 6.4 lb (2.9 kg) | 35.5 lb (16.1 kg) |
| Improvement in diastolic blood pressure | –5.7 mmHg | –1.6 mmHg |
One of the STEP programs’ more notable features was how few patients dropped out. In most drug trials, an average of 30% of drug trial participants drop out for various reasons. In the Step 5 trial, only 7% of participants left the program. This was probably due to the mild and rare side effects of Wegovy, the reduced risk factors, and the visible improvements in weight and waist that participants could experience for themselves.
Wegovy was approved by the FDA in mid-2021 for patients with a BMI greater than 30 or those with a BMI between 27 and 30 who have a relevant comorbidity such as high blood pressure, diabetes, or high cholesterol.
How can you get tirzepatide as a prescribed weight-loss medication?
You can’t get Zepbound from IsraelPharm right now due to a worldwide drug shortage.
At the beginning of October 2023, the FDA finally approved using Zepbound (tirzepatide) as a treatment for chronic weight management. However, it only started to reach the shelves of pharmacies in the first quarter of 2024, and supplies quickly ran out due to overwhelming demand. The conditions for which it has been approved are very similar to the ones for Wegovy, namely for people with obesity (BMI of 30 or greater) or people who are overweight (BMI 27 – 30) with at least one weight-related condition like high blood pressure, high cholesterol levels, obstructive sleep apnea, or cardiovascular disease.
What conclusions can we draw about the differences between Ozempic/Wegovy and Mounjaro/Zepbound?
As we said at the beginning, both Novo Nordisk and Eli Lilly have become the rage on the stock market, thanks in no small part to their participation in one of the biggest markets in the world – the demand for weight-loss treatments. There is an epidemic of obesity worldwide, and it’s pretty easy to foresee that the volume of annual sales of weight-control drugs could easily reach $100 billion by 2030, and Eli Lilly and Company and Novo Nordisk will, in all probability, control 80% of that market between them.
It’s a bit harder to understand why Eli Lilly has outstripped Novo Nordisk regarding share price performance. It may be that the impact of the new drug Zepbound is expected to both boost Eli Lilly’s share of the market and take a chunk out of Wegovy’s sales. This is not an area in which we can claim expertise, so let’s leave it with the saying that most advisors on investment end with … “past performance is no guarantee of future results.”
