Mounjaro, Diabetes, and Weight Loss: The Results Are In

A new study has confirmed that tirzepatide (Mounjaro) is the most effective weight loss drug ever for people with diabetes.

In 2022, tirzepatide (Mounjaro) was approved as a type 2 diabetes medication on the strength of trials showing that it offered unprecedented glycemic improvements. Diabetes Daily said that “it may prove to be the most effective type 2 diabetes drug ever developed.” Now, thanks to data just released, we have a much fuller understanding of Mounjaro and weight loss in people with diabetes.

The results: Participants in the SURMOUNT-2 trial (PDF) lost an average of 16 percent of their body weight (about 34 pounds) over 18 months. This amount of weight loss is better than the amount triggered by semaglutide (Ozempic, Wegovy, Rybelsus) and nearly as good as the huge loss associated with bariatric surgery.

Like Ozempic, Mounjaro mimics the effects of the hormone GLP-1, which is 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. When patients with diabetes take the drug, it reduces blood glucose levels while also helping them eat less. Mounjaro has all of those positive effects, but it additionally mimics another hormone, glucose-dependent insulinotropic polypeptide (GIP). The combination appears to be even more effective.

Timothy Garvey, MD, called the study “a landmark.” Dr. Garvey is the director of the diabetes research center at the University of Alabama at Birmingham; he presented the results at a special symposium at the American Diabetes Association’s annual Scientific Sessions conference.

Type 2 Diabetes and Weight Loss

It is more difficult to lose weight when you have type 2 diabetes . No matter the therapy — diet, medication, or bariatric surgery — people with diabetes invariably lose less weight than people without. “We don’t totally understand that,” says Garvey.

Consider semaglutide, which at its highest approved dose (2.4mg), confers about 10 percent loss of body mass in people with type 2 diabetes, according to the STEP 2 trial. But the STEP 1 trial found that people without diabetes will lose 15 percent of their bodyweight. It’s a big difference, according to Garvey:

“We really want medicines in diabetes to get weight loss into the 15 percent range or higher. Why? Because we know at that degree of weight loss, it’s sufficient to prevent a broad range of obesity-related complications.”

Garvey explained that though earlier trials suggested Mounjaro’s immense potential as an obesity medication for people with diabetes, the scale of that weight loss was unclear because the trials had been designed to prioritize the evaluation of glycemic control. The SURMOUNT-2 trial answers that question.

Weight Loss and Glycemic Improvement

The new trial evaluated two strengths of tirzepatide, 10mg and 15mg, in patients with obesity and type 2 diabetes. Study participants, who began the trial with an average A1C of 8.0 percent and a weight of 222 pounds, used the drug for a total of 72 weeks.

At the highest dose of tirzepatide:

Over 80 percent of participants lost at least 5 percent of their body weight
About 50 percent lost greater than 15 percent of their body weight
About 15 percent lost more than 25 percent of their body weight

Blood sugar improvements were similarly impressive:

A1C declined by about 2.1 percent, from 8.0 percent to 5.9 percent
More than 90 percent of participants met the American consensus glycemic target of <7.0 percent
55 percent achieved normal blood sugar levels (<5.7 percent)

“To think we could normalize blood sugar levels in type 2 diabetes,” Garvey stated, “it’s very impressive to me, let me put it that way.”

And despite the powerful glucose-lowering effect, there were very low rates of mild hypoglycemia, and a complete absence of severe hypoglycemia.

There were improvements in many other metabolic parameters, too: blood pressure, HDL cholesterol, triglycerides, and waist size. “These patients need to buy new clothes,” Garvey said. Fasting insulin levels dropped by 41 percent. “That’s a big decrease … it’s really indicative of an increase in insulin sensitivity.”

Like semaglutide (Ozempic) and other drugs in the GLP-1 receptor agonist family, tirzepatide (Mounjaro) is known to cause gastrointestinal side effects, though Garvey noted that only 21.9 percent of participants complained of nausea, which is much less than the highest doses of semaglutide.

“Symptoms occur early, patients kind of deal with them, and we don’t very often have to discontinue the medicine because of the side effects. They get better over time.”

For decades, a debate has raged in the clinical research community: Which is more important for type 2 diabetes management, glycemic control or weight loss? While experts have increasingly come to a consensus on the issue that weight loss is more important, Garvey believes that Mounjaro’s results put that debate to rest:

“With a medicine like this, the point is moot … The medicine that is best for diabetes control is also best for weight loss.

“Patients with type 2 diabetes and obesity have two diseases and both warrant optimal treatment … this is a therapeutic gap that tirzepatide could fill.”

High Prices Remain Problematic

When asked about the high price of Mounjaro, and whether it might exacerbate diabetes and obesity disparities, Garvey didn’t mince words.

“This kills me. These medicines are very expensive, but these costs limit access, and insurers don’t want to open the dam up and treat everyone.

“To me, it comes down to risk stratification. If you can identify the patients that need it the most … but that would imply a rational way of dealing with disease in the US, and it ain’t gonna happen any time soon.

“I just wish we had better access, and I wish that patients in the US were paying the same as patients in other countries.”

Garvey movingly described how some trial participants were in tears at the conclusion of the trial, knowing that they couldn’t afford to continue taking the drug that had helped them so much.

Garvey, like other experts, expects tirzepatide to win approval as a weight-loss medication for people without diabetes later this year. It’s difficult to speculate, however, on the ways that the change could affect access and affordability for people with diabetes that use or wish to use Mounjaro. There have been intermittent Mounjaro shortages since it was approved one year ago, possibly due to the huge number of patients that are using the medication off-label for weight loss.

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