Mounjaro: Its Powerful Potential to Treat Type 2 Diabetes & Obesity

Coverage of the ADA Scientific Sessions is brought to you by the ADA x BT1 Collab.

Recognizing obesity as a chronic disease is critical to supporting those living with it. While addressing the metabolic and physiological issues contributing to obesity, a sustainable weight loss treatment must reduce a person’s hunger while also increasing satiety. 

Here, experts discuss the impressive impact and future potential of using Mounjaro (tirzepatide) to treat obesity and type 2 diabetes. This medication is currently FDA-approved for the treatment of type 2 diabetes, but it could in the future be a potential treatment for people living with obesity who do not have type 2 diabetes. 

Presentation: SURMOUNT-1—Results of The First Phase 3 Obesity Trial with The Novel GIP/GLP-1 Receptor Agonist

Speakers at this ADA Scientific Sessions presentation included: Donna Ryan, MD (Pennington Biomedical), Jamy Ard, MD (Wake Forest School of Medicine), Louis Aronne, MD (Weill Cornell Medicine), Lee Kaplan, MD, Ph.D. (Mass. General Hospital), Carel le Roux, FRCP, Ph.D. (University of College Dublin), Sean Wharton, MD, PharmD (Wharton Medical Clinic), Ania Jastreboff, MD, Ph.D. (Yale University School of Medicine), Sriram Machineni, MD (University of North Carolina School of Medicine), and Juan Frias, MD (Velocity Clinical Research).

Looking at Mounjaro: A New GIP/GLP-1 Receptor Agonist

“It’s just as easy to lose weight as it ever was to gain weight,” said a study participant, quoted by Ania Jastreboff, MD, Ph.D. This statement sums up the potential of Mounjaro’s ability to help people living with obesity and type 2 diabetes across the globe. 

 Mounjaro is a once-weekly injectable medication from Lilly Diabetes. It is the first and only unimolecular dual GIP/GLP-1 receptor agonist. 

• glucose-dependent insulinotropic polypeptide (GIP)
• glucagon-like peptide-1 (GLP-1)

It has proven to result in significant reductions in A1c levels and body weight. Mounjaro works in several ways:

• It increases insulin production, but only when your blood sugar is rising—which makes the risk of low blood sugar minimal.
• It decreases your liver’s production of sugar.
• It slows down the speed at which your stomach empties food into your intestine. This helps manage your blood sugars after eating while also leaving you feeling full longer.

Through a series of studies over the past few years, Mounjaro has shown to have a big impact on weight loss, A1c and cholesterol in people living with type 2 diabetes

Research Results on the Benefits of Mounjaro

Compared to long-acting insulin or sulfonylureas, Mounjaro has performed well in research.

Weight loss: The most recent SURMOUNT-1 study consisted of 2,539 participants with an average starting body weight of 231 pounds. 

• At the lowest dose—5 mg—participants lost 15 percent of their body weight over 72 weeks.
• At higher doses—10 and 15 mg—participants lost about 20 percent of their body weight over 72 weeks.
• More than half of the participants taking the higher dose lost 20 percent of their body weight compared to only 1.3 percent taking a placebo.
• Many participants lost 22.5 percent of their body weight—about 52 pounds from a starting weight of 231 pounds.
• Up to 57 percent of participants reached a 20 percent weight reduction and sustained weight loss over the 72 weeks of treatment.
• All cardiometabolic measures improved, including blood pressure, triglycerides, body mass index (BMI), A1c and cholesterol.

Other noteworthy results from SURMOUNT-1 include:

• Prediabetes: More than 95 percent of participants with prediabetes reached normal blood sugar levels.
• Insulin use: Fasting insulin levels decreased by 4-5 units on Mounjaro, an average of 47 percent less insulin. 
• Waist circumference: The reduction in waist circumference was five times greater in those taking Mounjaro compared to a placebo.
• Total fat mass changes: 8.2 percent decrease on the placebo vs. 33.9 percent decrease taking Mounjaro.

In prior years, there were several notable studies on Moujaro, including SURPASS-3, SURPASS-5, and SURPASS-2. The most recent, phase 3 of SURPASS-4 included more than 13,000 participants. 

• A1c reduction: Trial participants with A1c levels starting at/above 8.0 percent experienced about a 2.5-point reduction. For example: 9.5 percent down to 7.0 percent. According to reports from SURPASS-4, 91 percent of participants achieved an A1c of 7% or lower, while 43 percent reached an A1c of 5.7% or lower. 
• Weight loss: Mounjaro showed the most significant weight loss compared to any other diabetes medication. The average weight loss after 52 weeks was about 25 pounds, with trial participants taking the highest dose (15 mg) losing about 27 pounds, and on the lowest dose (5 mg) about 17 pounds.
• Lessened risk of hypoglycemia compared to other medications: Yes, Mounjaro can potentially cause low blood sugars but the risk appears to be very minimal compared to taking insulin or a sulfonylurea drug.
• Reduction in triglycerides and cholesterol: After 52 weeks, the highest dose of Mounjaro reduced total cholesterol by about 5.6 percent, triglycerides by 22.5 percent, LDL cholesterol by 7.9 percent, VLDL by 21.8 percent, and increased HDL by 10.8 percent.

Looking at Efficacy + Safety of Current Treatments for Obesity

When comparing the existing methods of treating obesity, the following details were highlighted.

Intensive lifestyle therapy:

• Effective in theory but long-term execution is challenging for patients.
• Most effective when used in conjunction with other treatments

Ozempic (semaglutide):

• Introduced in 2021 for the treatment of type 2 diabetes and obesity
• GLP-1 agonists may not prevent obesity, but it helps overcome physiological issues that contribute to obesity.
• GLP-1 agonists can potentially reset a patient’s entire metabolic system.
• Mounjaro still results in greater weight loss than Ozempic.
• When patients stop taking Ozempic most patients regained the weight they lost, indicating a need to take a maintenance dose.
• Maintenance doses are critical for long-term weight management.

Bariatric surgery

• 30 percent initial weight loss with surgery
• Major improvements in the last 60 years
• Significantly safer today than a few decades ago
• But still not more effective long-term than intense lifestyle therapy
• Immediately after surgery, patients experience a significant decrease in appetite.
• Long-term, the reduced absorption of calories leads to increased hunger.

Mounjaro (tirzepatide):

• Introduced in 2022 for the treatment of type 2 diabetes (and eventually, obesity)
• This dual GLP-1 and GIP treatment is proving more effective than GLP-1 agonists alone.
• Weight loss success is similar to results seen in bariatric weight loss surgery.
• There is still no one-size-fits-all successful approach and Mounjaro is no different.
• In a study that allowed patients to stop taking Mounjaro after one year, most patients regained the weight they lost, indicating a need to take a maintenance dose.
• To maintain results, research is needed to determine maintenance dose vs. treatment dose.

Side-effects and Safety of Mounjaro

The overall safety review of Mounjaro is equivalent to other similar medications for obesity and type 2 diabetes.

The vast majority of side effects experienced with Mounjaro were related to digestive symptoms and discomfort. Side effects were significant in the first few weeks when the medication dose was gradually increased to the appropriate treatment dose. 

Over time, these side effects decreased dramatically once participants reached their treatment dose.

The most-reported side effects of Mounjaro in the SURMOUNT-1 trial included:

• Nausea
• Diarrhea
• Constipation
• Dyspepsia (heartburn)
• Vomiting
• Decreased appetite
• Abdominal pain
• Eructation (burping)

 Lesser-reported side effects included:

• Headache
• Hair loss
• Dizziness
• Injection site reaction

Mounjaro’s Potential in Treating Adolescents with Type 2 Diabetes

Many medications for type 2 diabetes have proven less effective in young people. A clinical trial is underway to determine the safety and efficacy of Mounjaro in this population.

With New Tools to Treat Obesity Comes Responsibility

With dramatically increasing rates of obesity across the United States and the globe, obesity is a serious condition that calls for greater intervention and accessible treatments.

“Obesity will not go away on its own,” said Wharton. “We need to manage it. We need to understand the tools we now have and use them well.”

Wharton specifically listed those he feels are most responsible for helping the people who need help treating obesity and type 2 diabetes, including providers, public health officials, pharmaceutical companies, insurance companies and patients themselves.

“We need to take obesity seriously,” said Wharton, “and we shouldn’t let these powerful tools go to waste.”

WRITTEN BY Ginger Vieira, POSTED 06/04/22, UPDATED 12/17/22

Ginger Vieira is the senior content manager at Beyond Type 1. She is also an author and writer living with type 1 diabetes, celiac disease, fibromyalgia and hypothyroidism. She’s authored a variety of books, including “When I Go Low” (for kids), “Pregnancy with Type 1 Diabetes,” and “Dealing with Diabetes Burnout.” Before joining Beyond Type 1, Ginger spent the last 15 years writing for Diabetes Mine, Healthline, T1D Exchange, Diabetes Strong and more! In her free time, she is jumping rope, scootering with her daughters, or walking with her handsome fella and their dog.