MOUNJARO® (TIRZEPATIDE) FOR WEIGHT LOSS

Like other well-known GLP-1 drugs—such as Wegovy®, made by competitor Novo Nordisk—Mounjaro® is a once-weekly injectable medication that helps regulate blood sugar levels. Currently, it is indicated for use in patients with type 2 diabetes, but it shows promise as a weight-loss medication as well.

Clinical trials found doses of tirzepatide effective in reducing hemaglobin A1C levels and assisting with weight loss. Early data suggests that it may even reduce the likelihood of cardiovascular events such as heart attack or stroke, though a trial tackling this question has not yet concluded. 

Mounjaro® is meant to be used alongside lifestyle changes, i.e. changes to food, sleep, and exercise. It is expected that the drug will work best when accompanied by coaching and support from trained professionals. 

The recommended starting dosage of Mounjaro® is 2.5 mg. After 4 weeks, doses may be increased in 2.5 mg increments, as tolerated, up to a maximum of 15 mg once weekly. Doses are set and monitored by a healthcare provider and may be adjusted to help patients meet their blood sugar, weight loss, and metabolic health goals.

As of May 2022, Mounjaro® is FDA-approved for use in patients with type-2 diabetes mellitus and not for weight loss alone. However, there is proof that its active ingredient is safe and effective in treating overweight or obesity. Just as it does in adults with type-2 diabetes, Mounjaro® can improve blood sugar levels in adults with insulin resistance or prediabetes—and is an effective tool for weight loss among both groups.

Mounjaro® works similarly to the other drugs in the GLP-1 family, but it contains an extra molecule that may give it a slight edge. 

The medication has a dual-action design, mimicking the action of not one but two incretin hormones involved in blood sugar control: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This unique dual action makes it the first-in-class medicine that acts on both of these receptors.

According to a press release published by Eli Lilly, “GIP is a hormone that may complement the effects of GLP-1 receptor agonists. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with GLP-1 receptor agonist, may result in greater effects on markers of metabolic dysregulation such as body weight, glucose and lipids.”

Why mimic incretin hormones?

Incretin hormones are released whenever food is consumed. Among other things, they help promote a feeling of fullness by delaying gastric emptying and activating the satiety centers of the brain. They also boost insulin production in the pancreas, and suppress glucagon production, both of which help normalize blood sugar. 

All of this happens in a glucose-dependent manner, which means incretin hormones—or their imitators, i.e. GLP-1 and GIP receptor agonists—are unlikely to cause severe hypoglycemia. 

What about your natural incretin hormones? Studies have found that people with overweight or obesity may have a reduction in incretin effects, particularly if they have had frequent weight fluctuations due to yo-yo dieting. GLP-1-type medication narrows the gap, making it easier to reach your goals and lower your metabolic set point.

Is Mounjaro® really all that special? All signs point to yes.

Results of the drug’s clinical trials were making headlines even prior to its FDA approval, and for good reason: Tirzepatide has, in two separate studies, blown some of its competitors out of the water. Read more about these trials—and their outcomes—below.

SURPASS-2 clinical trial

In a 2021 head-to-head trial, Eli Lilly’s Mounjaro® was found to be more effective at controlling blood sugar and helping patients lose weight than Novo Nordisk’s Ozempic® (semaglutide). This SURPASS-2 trial took place over the course of 40 weeks and participants saw, on average, A1C reductions of up to 2.30 percentage points vs. their baseline. This was compared to a 1.86 percentage point reduction achieved with semaglutide.

Perhaps even more interestingly, the same trial concluded that reductions in body weight were greater with tirzepatide than with semaglutide: Up to 5.5 kg more weight loss was seen with the former. Researchers hypothesize that this has to do with the medications’s unique dual action. 

A summary published in the New England Journal of Medicine states, “In patients with type 2 diabetes, a single molecule combining the glucose-dependent insulinotropic polypeptide receptor and GLP-1 receptor agonist may have a greater effect on glucose levels and weight control than selective GLP-1 receptor agonists.”

SURMOUNT-1 clinical trial

In the widely-publicized SURMOUNT-1 trial, Mounjaro® was examined specifically for weight loss and the treatment of obesity. It did not disappoint: At week 72, average weight loss was 15.0% for those on a 5 mg dose, 19.5% for those on a 10 mg dose, and 20.9% for those on a 15 mg dose. This was compared to weight loss of only 3.1% in participants taking a placebo.

Other trials and research

In an earlier study completed in 2018, doses of Lilly’s tirzepatide were pitted against dulaglutide—a.k.a. Trulicity®—and “showed significantly better efficacy with regard to glucose control and weight loss than did dulaglutide, with an acceptable safety and tolerability profile.” Side effects with tirzepatide were similar to those of dulaglutide and, in general, well tolerated. 

Other trials of Mounjaro® compared tirzepatide against a placebo or against more traditional therapies, including two long-acting insulin analogs. In all cases, tirzepatide at the highest dose of 15 mg/week has outperformed its opponents in A1C reduction and in overall weight loss.

Calibrate doctors are now prescribing Mounjaro® where available and clinically appropriate. Having new, even more effective tools for our members is incredibly powerful and will continue to accelerate the way we change the way the world treats weight.

Other GLP-1 medications currently available to Calibrate members include Wegovy®, Ozempic®, Rybelsus®, Saxenda®, and Trulicity®. Calibrate doctors will prescribe whichever medication will work best for you based on your unique needs and health insurance coverage.

When you join Calibrate, you’ll complete a Comprehensive Health Intake, including blood work, that your Calibrate doctor will carefully review before customizing your treatment plan and prescribing your medication. You may be eligible for tirzepatide or semaglutide even if you are already taking another type 2 diabetes medication such as metformin.

If your Calibrate medical team determines that Mounjaro®  is the right fit for you, they’ll walk you through all of the details on dosage, how to administer the medication, when to take it, and how it will work alongside your metabolic reset plan. 

The most common side effects of Mounjaro® include:

- Nausea

- Diarrhea

- Decreased appetite

- Vomiting

- Constipation

- Indigestion

- Stomach (abdominal) pain 

Keep in mind that these are not all the possible side effects of Mounjaro®. Talk to your health care provider about any side effects of Mounjaro® that become bothersome or that don’t go away. 

The medical team can offer recommendations and supportive care for any issues that arise.  If you experience any allergic reaction such as anaphylaxis or shortness of breath, please seek immediate medical care.

Mounjaro® is FDA-approved and is safe when used as prescribed. As with all prescription medications, there are warnings and contraindications to keep in mind prior to starting treatment with Mounjaro®. Your Calibrate doctor will discuss these with you and can answer any specific questions you might have about the risks of Mounjaro® as it pertains to your own health and medical history.

The below limitations, contraindications, and warnings are sourced directly from the FDA.

Limitations of use:

Mounjaro® is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 

- Mounjaro® has not been studied in patients with a history of pancreatitis 

- Mounjaro® is not indicated for use in patients with type 1 diabetes mellitus 

Contraindications:

Mounjaro® is contraindicated in patients with:

- A personal or family history of medullary thyroid carcinoma (MTC) 

- A personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 

- Known serious hypersensitivity to tirzepatide 

Warnings & precautions:

- Pancreatitis has been reported in clinical trials. Discontinue promptly if pancreatitis is suspected.

- Concomitant use with an insulin secretagogue or insulin may increase the risk of hypoglycemia. Reducing dose of insulin secretagogue or insulin may be necessary. 

- Hypersensitivity reactions have been reported. Discontinue Mounjaro® if suspected.

- Doctors are instructed to monitor kidney function in patients with renal impairment who are reporting severe adverse gastrointestinal reactions. 

- Use may be associated with gastrointestinal adverse reactions, sometimes severe. Has not been studied in patients with severe gastrointestinal disease and is not recommended in these patients.

- Mounjaro® has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Doctors are instructed to monitor patients with a history of diabetic retinopathy.

- Acute gallbladder disease has occurred in clinical trials. If cholelithiasis is suspected, gallbladder studies and clinical follow-up are indicated. 

Mounjaro® is the “next big thing” in weight loss and diabetes pharmacology. Usually, we’re skeptical of splashy new treatments or medications that stir up buzz in the medical weight loss field, but this one is different: It has real numbers—and impressive clinical trial results—to back it up. 

Here’s what you need to know about Mounjaro® at a glance:

- Mounjaro® (tirzepatide) is a dual GIP and GLP-1 receptor agonist and the very first medication of its class. It works similarly to GLP-1 receptor agonists like Ozempic® or Wegovy® but has a dual-action design that works on a second type of receptor: Glucose-dependent insulinotropic polypeptide (GIP). 

- As of May 2022, Moujaro™ is FDA-approved for use in adults with type-2 diabetes. However, there is proof that its active ingredient, tirzepatide, is safe and effective in treating overweight or obesity.

- Participants of the SURPASS-2 clinical trial of Mounjaro® (tirzepatide) saw, on average, A1C reductions of up to 2.3% vs. their baseline. The same trial also found that tirzepatide produced 5.5 kg more weight loss when compared against semaglutide. 

- Mounjaro® is now available in many pharmacies across the United States. Keep in mind that distribution began only recently, in June 2022, and the drug may not be available everywhere at this time. 

- Calibrate doctors are now prescribing Mounjaro® to patients where clinically appropriate and insurance-eligible. You may be prescribed a different GLP-1 medication depending on your unique health history and profile.