For Weight Loss and Blood Sugar, Mounjaro May Work Better Than Ozempic

Drugs mimic hormones

Semaglutide belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists. It mimics the GLP-1 hormone, which is released in the gut in response to eating.

Tirzepatide also mimics the GLP-1 hormone, as well as the glucose-dependent insulinotropic polypeptide (GIP), another hormone released after eating.

The dual action of tirzepatide is thought to be the reason that some studies show it is more effective for blood sugar control and weight loss than single-acting drugs like semaglutide.

The new meta-analysis included only studies that tested the injectable forms of semaglutide and tirzepatide, which are given beneath the skin.

Of the 22 trials included in the meta-analysis, two involved direct comparisons between semaglutide and tirzepatide, the SURPASS-2 trial and another smaller trial.

The other 20 trials compared either semaglutide or tirzepatide with a common comparator, such as an inactive placebo, basal insulin, or other GLP-1 receptor agonist drugs. These studies were used to provide indirect comparisons between semaglutide and tirzepatide.

Overall, the studies included data from 18,472 patients with a diagnosis of type 2 diabetes.

The studies assessed once-weekly maintenance doses of tirzepatide of 5, 10 or 15 milligrams, or semaglutide at 0.5, 1.0 or 2.0 milligrams. Studies lasted at least 12 weeks.

Semaglutide is also marketed as Rybelsus, an oral treatment for type 2 diabetes, and as Wegovy, an injectable treatment for obesity.

Tirzepatide is not approved yet in the United States as an anti-obesity treatment.

Blood sugar reduction

The 15-milligram dose of tirzepatide had the largest effect on blood sugar, lowering HbA1c by 2% on average compared to a placebo.

Tirzepatide 10 mg lowered HbA1c by an average of 1.86%, and semaglutide 2.0 mg by an average of 1.62%.

HbA1c is a blood test used to monitor blood glucose control in people with diabetes.

Each of the tirzepatide doses lowered HbA1c more than the corresponding low, medium and high doses of semaglutide, researchers found.

A reduction in HbA1c by at least 0.5% is considered “clinically important,” according to the National Institute for Health and Care Excellence.

Body weight reduction

Reductions in body weight were greatest with tirzepatide, when compared to placebo: 24.2 pounds for the high dose, 19.3 pounds for the medium dose, and 13.6 pounds for the low dose, on average.

In contrast, people taking semaglutide lost an average of 11.6 pounds on the high dose, 9.8 pounds on the medium dose, and 6 pounds on the low dose.

When the two drugs were compared directly, the high and medium doses of tirzepatide resulted in more weight loss than all three doses of semaglutide.

The low dose of tirzepatide was more effective for weight loss than the medium and low doses of semaglutide.

“In summary, the three tirzepatide doses were more effective than the three respective semaglutide doses, with the difference between the two drugs being larger with the higher doses,” the authors said in a news release.

Negative side effects

All doses of semaglutide and tirzepatide increased the risk of nausea, vomiting and diarrhea compared to placebo. The highest dose of tirzepatide was associated with the greatest increased risk of these gastrointestinal side effects.

The highest dose of tirzepatide also had a greater risk of vomiting than the medium and low doses of semaglutide, and a greater risk of nausea than the low dose of semaglutide.

There were no significant differences between the two drugs and placebo for the risk of serious adverse events.

Real world implications

Dr. Caroline Messer, an endocrinologist at Northwell Health’s Lenox Hill Hospital in New York City, said the weight loss seen in the studies included in the meta-analysis are similar to what she has seen in the clinic.

“It’s almost double the weight loss in most of my patients [with tirzepatide],” she told Healthline. “So definitely tirzepatide is more effective.”

Dr. Jennifer Cheng, an endocrinologist at Hackensack Meridian Jersey Shore University Medical Center in New Jersey, pointed out that while tirzepatide resulted in greater weight loss than semaglutide at the higher doses, the HbA1c reduction is similar for the two drugs, with tirzepatide coming out slightly ahead.

However, “only two of the trials [included in the meta-analysis] were a head-to-head comparison,” Cheng told Healthline, meaning “only two of the 22 trials compared the drugs [directly] to each other.”

In addition, “we are still waiting on long-term cardiovascular safety data for tirzepatide,” she said, “as opposed to semaglutide, which has long-term cardiovascular safety data [showing] it helps prevent cardiovascular events.”

Messer pointed out that the head-to-head trials of the two drugs only included patients with diabetes, so the results may be different for people using the drug primarily to lose weight.

In July, drug maker Eli Lilly announced results from two trials of tirzepatide (Mounjaro) in adults who were overweight or had obesity, excluding those with type 2 diabetes. These showed that people lost around 26% of their weight after 84 to 88 weeks, using a dose of 10 or 15 milligrams.

Balancing benefits, risks and cost

In terms of deciding which drug to use for the treatment of type 2 diabetes, Cheng recommends that people talk with their doctor about the risks and benefits of each medication.

However, while clinical trials provide an overview of the average rates of side effects experienced by people, individuals may have a different experience with some drugs.

In her clinic, Messer’s patients tend to tolerate tirzepatide better than semaglutide. In addition, she said constipation is usually more of a concern than diarrhea for people taking these drugs.

Cost may also play a part in people’s decisions. The total cost of 72 weeks of tirzepatide was $17, 527, compared with $22,878 for 68 weeks of semaglutide, according to a recent study. In addition, a person’s insurance may not cover the cost of the drug, especially if it is prescribed off-label.

Eli Lilly has completed an application to the FDA for the use of tirzepatide in chronic weight management, the company announced in August.

Messer said FDA approval of this drug can help patients paying out of pocket.

“We have a lot of patients who don’t have diabetes, but are paying out of pocket [for tirzepatide], using coupons to cover the cost, and doing whatever they can to get hold of it,” she said, “just because it’s so unbelievably powerful in terms of controlling impulses and hunger.”

Doctors can still prescribe Eli Lilly’s Mounjaro off-label for obesity, but “off-label use of this medication could potentially increase demand,”said Cheng, “and lead to decreased drug availability.”

Earlier this year, the FDA added Mounjaro to its drug shortages database, citing increased demand, but most doses of the drug are now available again, agency data shows.

Takeaway

A meta-analysis of 22 studies compared tirzepatide (Mounjaro) and semaglutide (Ozempic), drugs used to treat type 2 diabetes. Tirzepatide was superior for blood sugar control, although only slightly, and also for weight loss.

Certain side effects were greater with tirzepatide, including vomiting and nausea. Experts say it is important to consider these side effects when deciding which drug to use.

Tirzepatide is not yet approved in the United States for obesity, but can be prescribed off-label for that purpose. Earlier this year, though, the drug was facing shortages due to high demand.