SURPASS-PEDS: Exploring Mounjaro Clinical Data for Pediatric Patients Aged 10 Years and Older With Type 2 Diabetes
Brian Benneyworth, MD: Hello, my name is Brian Benneyworth,
On behalf of Lilly, I’d like to thank you for taking the time out of your busy schedule to join us for this exciting event.
I’m here today with Dr. Daniel Nadeau discussing a clinical study evaluating Mounjaro (tirzepatide) for pediatric patients 10 to less than 18 years of age with type 2 diabetes.
As I have practiced as a pediatric intensive care specialist, I’m eager to discuss the clinical relevance of Mounjaro for the pediatric population—especially as we think about treating patients with type 2 diabetes as early after diagnosis as possible.
In my practice, I’ve seen pediatric patients newly diagnosed with type 2 diabetes in need of options.
That’s why having another treatment to help these patients manage their type 2 diabetes is crucial.
Dr. Nadeau, welcome! Would you like to tell us a little bit about yourself?
Daniel Nadeau, MD: Sure! I am Daniel Nadeau, an endocrinologist based in Aliso Viejo, California. I am board-certified in diabetes, metabolism, and endocrinology, and I’ve been practicing endocrinology for over 20 years.
You know, it’s an honor to share these findings with you.
Brian Benneyworth, MD: Thank you for joining me, Dr. Nadeau.
I look forward to reviewing the clinical results of SURPASS-PEDS—a pivotal trial evaluating Mounjaro in pediatric patients aged 10 years and older with type 2 diabetes—and hearing your valuable perspective on this study.
Before we begin, let me provide a roadmap of what we will be covering today:
First, we’ll discuss the disease state of pediatric type 2 diabetes, including its incidence in the United States and clinical considerations.
Then we will review SURPASS-PEDS study design in detail.
We will continue by exploring SURPASS-PEDS primary and key secondary endpoint results, followed by the safety results.
Next, we will transition to the clinical results of Mounjaro in adults with type 2 diabetes, and we will review how SURPASS-PEDS fits within the SURPASS clinical program.
Brian Benneyworth, MD: And finally, we will conclude with guidance on initiating Mounjaro for appropriate adult and pediatric patients with type 2 diabetes.
Let’s get started!
First, I’d like to review the Indication and Boxed Warning for Mounjaro.
Mounjaro is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.
Mounjaro also has a Boxed Warning related to the risk of thyroid C-cell tumors.
In both male and female rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures.
It is unknown whether Mounjaro causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans as the human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.
Mounjaro is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2.
Counsel patients regarding the potential risk for MTC with the use of Mounjaro and inform them of symptoms of thyroid tumors (for example, a mass in the neck, dysphagia, dyspnea, or persistent hoarseness).
Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Mounjaro.
Now, I’d like to open our discussion by asking you:
What is the incidence of pediatric type 2 diabetes in the United States, and how has it changed over time?
Daniel Nadeau, MD: Great question.
First, there has been a significant increase in type 2 diabetes in the pediatric population in recent years.
Based on a CDC study on trends in diabetes among patients aged 10 to 19 years old in the US, the incidence of type 2 diabetes has doubled between 2002 and 2018.
That’s about a 5 percent annual increase in new cases of type 2 diabetes!
Daniel Nadeau, MD: Let’s also remember that type 2 diabetes in pediatric patients may be a more aggressive disease compared with adult-onset type 2 diabetes.
Therefore, early detection and intervention for type 2 diabetes may improve clinical outcomes.
Yet, historically, there have been fewer FDA-approved treatment options for pediatric patients with type 2 diabetes than for adults.
Brian Benneyworth, MD: Thank you for providing this context, Dr. Nadeau.
It underscores the importance of having another approved treatment option for pediatric patients with type 2 diabetes.
Now, let’s dive into the SURPASS-PEDS study.
Can you walk us through the trial design?
Daniel Nadeau, MD: Of course, Brian!
SURPASS-PEDS was a phase 3, double-blind, placebo-controlled, multicenter, multinational trial.
A total of 99 pediatric participants 10 years of age and older with type 2 diabetes, inadequately controlled with at least 1000 milligrams of metformin per day, or basal insulin, or both, were enrolled.
Regardless of whether they were in the Mounjaro or placebo treatment groups, they continued to receive either metformin, basal insulin, or both as background therapy throughout the study.
Let me now describe the structure of the study in more detail.
The first part was a 4-week screening period, after which participants entered the 30-week, double-blind treatment period.
Here, participants were randomized to receive once-weekly Mounjaro 5 or 10 milligrams, or placebo.
For those receiving Mounjaro, the dose was initiated at 2.5 milligrams for 4 weeks and then escalated by 2.5 milligrams every 4 weeks until the assigned maintenance dose was reached.
Following this, there was a 22-week open-label period during which all participants received Mounjaro plus metformin and/or basal insulin.
Of note, participants assigned to the placebo arm switched to the Mounjaro 2.5-milligram initiation dose and then continued on the Mounjaro 5 milligrams for the remainder of the study.
Those who were assigned to Mounjaro 5 or 10 milligrams continued on the same dose through week 52.
A 30-day post-treatment safety follow-up period was conducted at the end of the open-label period.
Brian Benneyworth, MD: Thank you for that thorough description of the study design!
It helps to establish the foundation for the efficacy and safety results, which we will review shortly.
But first, can you tell us about the primary and secondary endpoints?
Daniel Nadeau, MD: Yes!
The primary endpoint was the change in A1C from baseline to week 30 for the pooled Mounjaro 5- and 10-milligram doses, compared to placebo.
Several key secondary efficacy endpoints were also evaluated, as shown here.
For today’s discussion, we will focus on the following 3:
The change in A1C from baseline for the individual 5- and 10-milligram doses of Mounjaro compared to placebo
The percentage of participants who achieved an A1C of less than or equal to 6.5 percent, and
The percent change in body mass index, or BMI, from baseline at week 30
Brian Benneyworth, MD: Thank you!
So, we know that the study participants were pediatric patients with type 2 diabetes, but I would like to delve into the specifics.
Let’s take a closer look at who was eligible for this study.
Daniel Nadeau, MD: Absolutely!
Eligible study participants were pediatric patients 10 to less than 18 years of age with a diagnosis of type 2 diabetes.
They had an A1C greater than 6.5 percent and less than or equal to 11 percent at screening.
They were also receiving treatment with lifestyle measures, such as diet and exercise, and at least 1000 milligrams of metformin per day, or basal insulin, or both.
And they had a body weight greater than or equal to 50 kilograms, or about 110 pounds, and a BMI greater than the 85th percentile of the general age- and sex-matched population for that country or region.
As shown here, the baseline characteristics were similar among the treatment groups.
About 44 percent of the participants were between 10 and 14 years old, and 56 percent were between 15 and 17 years old.
Daniel Nadeau, MD: The mean A1C was 8 percent; the mean BMI was 35 kilograms per meter squared; and the mean baseline weight was 97 kilograms, or about 214 pounds; and the mean duration of type 2 diabetes was 2.4 years.
In terms of background therapies, 8 percent of patients were on basal insulin only, 23 percent were on metformin plus basal insulin, and 69 percent were on metformin only.
Brian Benneyworth, MD: Now what everybody’s been waiting for—the results!
Let’s start with the primary efficacy outcome.
What were the findings regarding change in A1C?
Daniel Nadeau, MD: Mounjaro demonstrated superior A1C reduction with both doses compared to placebo at 30 weeks.
As a reminder, all patients also received metformin and/or basal insulin as background therapy throughout the study.
Mean A1C reductions with Mounjaro ranged from 1.9 percent to 2.2 percent, compared to 0.2 percent with placebo.
Brian Benneyworth, MD: And how many patients reached the A1C target of less than or equal to 6.5 percent recommended by the International Society for Pediatric and Adolescent Diabetes, or ISPAD?
Daniel Nadeau, MD: Significantly more patients on Mounjaro achieved the ISPAD-recommended A1C target of less than or equal to 6.5 percent at 30 weeks—between 68 percent and 81 percent in the Mounjaro treatment groups compared to 28 percent in the placebo group.
Brian Benneyworth, MD: That’s notable!
For context, the A1C target recommended by the American Diabetes Association—less than 6.5 percent—is very similar to the A1C target set by ISPAD.
Daniel Nadeau, MD: Yes, I was excited to see these results!
The change in A1C through 52 weeks was also evaluated.
As a reminder, the double-blind period switched to the open-label period at week 30, during which the placebo group initiated Mounjaro 2.5 milligrams for 4 weeks and then continued on Mounjaro 5 milligrams for the remainder of the study.
Starting from a mean baseline A1C of 8.0 percent, the change in A1C at week 52 was minus 2.1 percent and minus 2.3 percent with Mounjaro 5 and 10 milligrams, respectively;
minus 2.2 percent with the pooled Mounjaro doses;
and minus 1.5 percent in the placebo-to-Mounjaro 5-milligram group.
Brian Benneyworth, MD: Now, continuing with the secondary endpoints:
What can you tell us about the changes in BMI?
Daniel Nadeau, MD: First, as you’re aware, BMI is used in pediatric patients instead of weight because they are continuing to grow, and any changes in weight need to be normalized for changes in height.
At 30 weeks, Mounjaro demonstrated superior BMI reduction across both doses compared to placebo.
The percent change in BMI from baseline ranged from minus 6.9 percent to minus 10.8 percent in the Mounjaro treatment groups compared to minus 0.5 percent in the placebo group.
Similar to the A1C results, the percent change in BMI from baseline at 52 weeks was also examined.
Starting from a baseline BMI of 35 kilograms per meter squared, the BMI percent change at 52 weeks was minus 8.9 percent and minus 15.1 percent with Mounjaro 5 and 10 milligrams, respectively;
minus 12 percent with the pooled Mounjaro doses;
and minus 4.8 percent with placebo.
As an important note, Mounjaro is not indicated for weight loss.
Brian Benneyworth, MD: Efficacy is only part of the story.
Let’s discuss safety, which is paramount, particularly in a pediatric population.
What were the most common adverse events?
Daniel Nadeau, MD: The most common adverse events occurring in at least 5 percent of patients included diarrhea, nausea, vomiting, upper abdominal pain, abdominal pain, dyspepsia, headache, oropharyngeal pain, cough, hyperglycemia, nasopharyngitis, decreased appetite, anxiety, gastroenteritis, injection-site reaction, and tonsillitis.
Treatment discontinuations due to common adverse events were 6 percent in the Mounjaro 5-milligram group, 0 percent in the Mounjaro 10-milligram and placebo groups, and 3 percent in the pooled Mounjaro doses group.
Before moving on, I would also like to highlight the Select Important Safety Information related to acute kidney injury due to volume depletion and severe gastrointestinal adverse reactions:
The majority of reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea.
Monitor renal function in patients reporting adverse reactions to Mounjaro that could lead to volume depletion, especially during dosage initiation and escalation of Mounjaro.
Daniel Nadeau, MD: In addition, use of Mounjaro has been associated with gastrointestinal adverse reactions, sometimes severe and is not recommended in patients with severe gastroparesis.
To learn more, please read the Important Safety Information.
Brian Benneyworth, MD: Dr. Nadeau, what about hypoglycemia?
That’s always a concern with antihyperglycemic medications, especially in pediatric patients.
Daniel Nadeau, MD: Agreed, Brian!
In patients with a baseline use of basal insulin with or without metformin, hypoglycemia—defined as a blood glucose level of less than 54 milligrams per deciliter—occurred in 3 out of 10 patients, or 30 percent, in the Mounjaro 5-milligram group;
in 3 out of 11 patients, or 27 percent, in the Mounjaro 10-milligram group;
and in 1 out of 10 patients, or 10 percent, in the placebo group.
And in patients with baseline use of metformin alone, hypoglycemia occurred in 2 out of 22 patients, or 9 percent, in the Mounjaro treatment groups, and in 1 out of 24 patients, or 4 percent, in the placebo group.
Severe hypoglycemia was defined as episodes requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
In this trial, there was no incidence of severe hypoglycemia reported in any of the treatment groups.
I also wanted to note that the Select Important Safety Information related to hypoglycemia with concomitant use of insulin secretagogues or insulin, as using Mounjaro with these medications may increase the risk of hypoglycemia.
For more information, please read the Important Safety Information.
Brian Benneyworth, MD: Now, let’s turn our attention to Tanner staging and height, additional considerations to keep in mind when managing pediatric patients with type 2 diabetes.
Dr. Nadeau, can you discuss these parameters?
Daniel Nadeau, MD: Yes, Tanner staging is classified into five stages—from Stage 1, which is prepubertal, to Stage 5, which represents full maturity.
Here we can see baseline Tanner stages for patients in the Mounjaro and placebo treatment groups.
In addition, let’s take a moment to review the changes in height over 52 weeks.
Daniel Nadeau, MD: Height expressed in centimeters and height standard deviation score, or SDS, which accounts for the patients’ mean height for their age and sex, were assessed across the Mounjaro and placebo treatment groups.
Brian Benneyworth, MD: Thank you for that detailed review of the SURPASS-PEDS results, Dr. Nadeau!
Now, I think it’s valuable to step back and see how these findings in pediatric patients fit within the broader clinical program for Mounjaro.
Mounjaro was previously approved for use in adult patients with type 2 diabetes, so, Dr. Nadeau, can you provide a brief overview of the SURPASS clinical program in adults to help inform our overall perspective of Mounjaro?
Daniel Nadeau, MD: I’d be happy to!
Let’s take a moment to review what we learned from the SURPASS-1 through SURPASS-5 studies.
In adults with type 2 diabetes, Mounjaro was studied as monotherapy and as an add-on to various standard-of-care medications, including oral antihyperglycemic agents and basal insulin.
We can see here that a similar study design was used in each trial, where patients were randomized to receive Mounjaro at 5, 10, or 15 milligrams; placebo; or an active comparator.
Let’s take a closer look at the 2 studies in which placebo was used as a comparator: SURPASS-1 and SURPASS-5.
In SURPASS-1, Mounjaro was studied as monotherapy in adults with type 2 diabetes who had inadequate glycemic control with diet and exercise.
In SURPASS-5, Mounjaro was studied in adults with type 2 diabetes who had inadequate glycemic control on insulin glargine, with or without metformin.
Now, let’s focus on clinical trials in which Mounjaro was studied as an add-on to various oral antihyperglycemic medications.
In SURPASS-2, Mounjaro was studied versus Ozempic® 1 milligram in adults with type 2 diabetes who had inadequate glycemic control on stable doses of metformin alone.
In SURPASS-3, Mounjaro was compared with Tresiba® as an add-on to metformin, with or without an SGLT2 inhibitor, in adults with type 2 diabetes who had inadequate glycemic control on their regimen.
Finally, in SURPASS-4, Mounjaro was evaluated versus insulin glargine as an add-on to 1 to 3 oral antihyperglycemic medications—metformin, a sulfonylurea, and/or an SGLT2 inhibitor—in adults with type 2 diabetes who had increased cardiovascular risk.
Daniel Nadeau, MD: Now, with the approval of Mounjaro for pediatric patients aged 10 years and older, let me show you a comprehensive view of A1C results across studies.
In adults and pediatric patients 10 years of age and older, Mounjaro delivered superior A1C reduction across all 6 clinical trials.
On the far left, as previously discussed, in pediatric patients with type 2 diabetes, we see superior A1C reductions with Mounjaro 5 and 10 milligrams compared to placebo when added to metformin and/or basal insulin.
Moving to the right, in adults with type 2 diabetes, we see that in SURPASS-1 through SURPASS-5, all 3 doses of Mounjaro delivered superior A1C reductions when studied across a variety of background therapies and comparators.
The A1C reduction from baseline in adult patients ranged from 1.7 percent to 2.4 percent with Mounjaro and from 0.1 percent to 1.9 percent with comparators.
Brian Benneyworth, MD: Earlier, we reviewed the safety of Mounjaro in pediatric patients with type 2 diabetes.
Now, let’s take a moment to look at the safety results from the studies in adults.
Dr. Nadeau, as a clinician specializing in adult care, could you walk us through those findings?
Daniel Nadeau, MD: Absolutely, Brian!
Let’s take a look at common adverse reactions observed in placebo-controlled trials.
In the pool of placebo-controlled trials, adverse reactions reported in at least 5 percent of patients taking Mounjaro included nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain.
Discontinuation rates due to gastrointestinal-related adverse events ranged from 3 percent to 7 percent in the Mounjaro groups versus 0 percent in the placebo group.
In placebo-controlled trials, when Mounjaro was used as monotherapy, the incidence of hypoglycemia and severe hypoglycemia was 0 percent across all Mounjaro treatment groups.
In the placebo group, the incidence of hypoglycemia was 1 percent and the incidence of severe hypoglycemia was 0 percent after 40 weeks.
In placebo-controlled trials, when Mounjaro was used as an add-on to insulin glargine, with or without metformin, the incidence of hypoglycemia ranged from 14 percent to 19 percent for patients receiving Mounjaro 5, 10, or 15 milligrams, and was 13 percent for placebo.
The incidence of severe hypoglycemia ranged from 0 percent to 2 percent in the Mounjaro groups, with no reported incidence for placebo.
Thinking back to the SURPASS-PEDS safety results, the incidence of adverse reactions reported in pediatric patients treated with Mounjaro 5 and 10 milligrams were consistent with Daniel Nadeau, MD: those described for adult patients with type 2 diabetes, with the exception of higher incidence of vomiting, abdominal pain, and hypoglycemia.
Brian Benneyworth, MD: So now we’ve reviewed the key efficacy and safety results across 6 clinical trials, let’s focus on how we get the appropriate patients started on Mounjaro.
Could you please tell us about the dosing and administration?
Daniel Nadeau, MD: Yes, I’ll start with adult patients.
There are 6 available doses of once-weekly Mounjaro—2.5, 5, 7.5, 10, 12.5, and 15 milligrams.
Patients should be initiated on the 2.5-milligram dose once weekly.
This dose is for treatment initiation only and is not intended for glycemic control.
After 4 weeks, increase the dose to 5 milligrams of Mounjaro once weekly.
If additional glycemic control is needed, increase the dose by 2.5 milligrams after at least 4 weeks on their current dose, up to a maximum dose of 15 milligrams once weekly.
I always recommend my adult patients follow the recommended dosage escalation to reduce the risk of gastrointestinal adverse reactions.
Of course, patients should be assessed for tolerability and adverse events before increasing a dose of Mounjaro.
Brian Benneyworth, MD: So, moving on to pediatric patients with type 2 diabetes, how many doses of Mounjaro are available for pediatric patients aged 10 years and older?
And how does the dosing in pediatric patients compare to the dosing in adult patients?
Daniel Nadeau, MD: Well, for pediatric patients, there are 4 available doses of once-weekly Mounjaro—2.5, 5, 7.5, and 10 milligrams.
The dosing and escalation approach is similar to that in adults.
Patients start with a 2.5-milligram dose, which is not intended for glycemic control, once weekly for 4 weeks.
Then, they continue on a 5-milligram dose for at least 4 weeks.
After that, based on individual glycemic response and tolerability, they may either remain at 5 milligrams or increase by 2.5-milligram increments after at least 4 weeks.
One important difference to note is that the maximum dose for pediatric patients is 10 milligrams administered once weekly.
Brian Benneyworth, MD: Are there any considerations and counseling tips related to the administration of Mounjaro to pediatric patients 10 years of age and older that you’d like to provide to caregivers?
Daniel Nadeau, MD: Yes, the initial conversation about starting an injectable medication is critical.
The Mounjaro pen is designed with the patient in mind — it is a single-use, once-weekly auto-injection pen, with a hidden needle.
If a demo pen like this one is available, it could be used to show patients and their parents or guardians how to prepare and inject Mounjaro before administering it for the first time.
It is important to explain that Mounjaro should be injected subcutaneously in the abdomen or thigh, or another person should inject it in the back of the upper arm.
A caregiver may give Mounjaro injections, or a patient may self-inject if a healthcare provider determines that it is appropriate.
Brian Benneyworth, MD: Thank you for providing this additional information, Dr. Nadeau!
This has been a very insightful discussion!
Before we wrap up with our key takeaways, I would like to address some of the questions that our viewers might have about the SURPASS-PEDS study.
Dr. Nadeau, you mentioned earlier that patients in both treatment arms continued to receive metformin and/or basal insulin with Mounjaro.
Please explain to the viewers our rationale for the inclusion of both metformin and basal insulin as background therapies.
Daniel Nadeau, MD: Of course, Brian!
As we all know, both metformin and insulin are standard-of-care medications for type 2 diabetes.
In clinical practice, pediatric patients with type 2 diabetes present at different stages of disease progression.
Some may be at a relatively early point in their disease course and are treated with metformin alone.
Others may have more advanced disease or more severe hyperglycemia and have already required the addition of basal insulin.
Brian Benneyworth, MD: That makes sense! And thank you for the explanation.
Another question: The maximum dose for pediatric patients 10 years and older is 10 milligrams, which is notably lower than the maximum 15-milligram dose that we use in adults.
Can you provide more information about this difference?
Daniel Nadeau, MD: Yes!
Both 5- and 10-milligram doses were evaluated in the SURPASS-PEDS trial, which included patients with a minimum body weight of 50 kilograms, or about 110 pounds.
A maximum dose of 10 milligrams was selected for the trial based on pharmacokinetic and pharmacodynamic exposure-response modeling, which predicted that this dose in pediatric patients meeting that weight criterion would provide the equivalent of adult exposure levels associated with clinically significant glycemic efficacy.
Brian Benneyworth, MD: Okay, next question is about managing hypoglycemia:
What steps should be taken to manage the risk of hypoglycemia in pediatric patients using an insulin secretagogue or insulin with concomitant use of Mounjaro?
Daniel Nadeau, MD: The risk of hypoglycemia may be lowered by a reduction in dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin.
Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on signs and symptoms of hypoglycemia.
Healthcare providers should use their clinical judgement and consider the patient’s individual needs when adjusting doses of concomitant antihyperglycemic medications.
Brian Benneyworth, MD: This next question is about mitigating the risk of gastrointestinal adverse events:
What counseling tips would you provide to mitigate gastrointestinal adverse events in pediatric patients?
Daniel Nadeau, MD: First of all, when starting Mounjaro, it is important to follow the recommended dosage escalation to reduce the risk of gastrointestinal adverse reactions.
In addition, I would advise patients to eat smaller more frequent meals, for example, splitting 3 daily meals into 4 smaller meals, and to stop eating when they feel full.
Eating bland foods like toast or crackers, and avoiding fatty foods may also help with nausea.
Brian Benneyworth, MD: Great, thank you so much for answering these questions.
As we wrap up, let’s highlight the overall key takeaways.
What would you say are the main points clinicians should remember?
Daniel Nadeau, MD: First, in SURPASS-PEDS, the efficacy and safety of Mounjaro was evaluated in pediatric patients 10 years of age and older with type 2 diabetes as an add-on to metformin and/or basal insulin.
Mounjaro was also studied in adults 18 years of age and older as monotherapy and as an add-on to various type 2 diabetes standard-of-care medications.
Daniel Nadeau, MD: In terms of results, Mounjaro demonstrated superior A1C reduction and unmatched effects on body weight across the 6 SURPASS clinical trials, including SURPASS-1 through SURPASS-5 in adults and SURPASS-PEDS.
Regarding safety, the incidences of adverse reactions reported in pediatric patients treated with Mounjaro 5 and 10 milligrams were consistent with those reported for adult patients with type 2 diabetes, with the exception of a higher incidence of vomiting, abdominal pain, and hypoglycemia.
Brian Benneyworth, MD: With the SURPASS-PEDS trial, we now have evidence supporting Mounjaro as a treatment option for pediatric patients 10 years of age and older with type 2 diabetes.
Dr. Nadeau, thank you for helping our viewers understand what this means for clinical practice!
Daniel Nadeau, MD: Thank you for having me and giving me the opportunity to share these results!
Brian Benneyworth, MD: For more information on SURPASS-PEDS, please visit mounjaro.com/hcp/peds.
Thank you for joining!
[Select Important Safety Information is read in full by voiceover]
Contraindications
Mounjaro is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with known serious hypersensitivity to tirzepatide or any of the excipients in Mounjaro. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with Mounjaro.
Risk of Thyroid C-cell Tumors
Counsel patients regarding the potential risk for MTC with the use of Mounjaro and inform them of symptoms of thyroid tumors (for example, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Mounjaro. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease.
Significantly elevated serum calcitonin values may indicate MTC and patients with MTC usually have calcitonin values greater than 50 nanograms per liter. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated.
Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.
Acute Pancreatitis
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, or Mounjaro. Observe patients for signs and symptoms, including persistent or severe abdominal pain sometimes radiating to the back, which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue Mounjaro and initiate appropriate management.
Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin
Concomitant use with an insulin secretagogue (for example, sulfonylurea) or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. The risk of hypoglycemia may be lowered by reducing the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
Hypersensitivity Reactions
Serious hypersensitivity reactions (for example, anaphylaxis and angioedema) have been reported in patients treated with Mounjaro. If hypersensitivity reactions occur, discontinue use of Mounjaro; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous serious hypersensitivity to tirzepatide or any of the excipients in Mounjaro. Use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist because it is unknown if such patients will be predisposed to these reactions with Mounjaro.
Acute Kidney Injury Due to Volume Depletion
There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, or Mounjaro. The majority of reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Mounjaro that could lead to volume depletion, especially during dosage initiation and escalation of Mounjaro.
Severe Gastrointestinal Adverse Reactions
Use of Mounjaro has been associated with gastrointestinal adverse reactions, sometimes severe. In the pool of placebo-controlled trials in adults, severe gastrointestinal adverse reactions occurred more frequently among patients receiving Mounjaro (5 milligrams 1.3 percent, 10 milligrams 0.4 percent, 15 milligrams 1.2 percent) than placebo (0.9 percent). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. Mounjaro is not recommended in patients with severe gastroparesis.
Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Mounjaro has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
Acute Gallbladder Disease
In placebo-controlled clinical trials in adults, acute gallbladder disease was reported by 0.6 percent of Mounjaro-treated patients and 0 percent of placebo-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.
Pulmonary Aspiration During General Anesthesia or Deep Sedation
Mounjaro delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Mounjaro.
Adverse Reactions in Adults
The most common adverse reactions reported in greater than or equal to 5 percent of Mounjaro-treated patients in placebo-controlled trials were nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain.
Drug Interactions
When initiating Mounjaro, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia. Mounjaro delays gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications, so caution should be exercised.
Pregnancy
Limited data on Mounjaro use in pregnant women are available to inform on drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on animal reproduction studies, there may be risks to the fetus from exposure to tirzepatide. Use only if potential benefit justifies the potential risk to the fetus.
Lactation
In a single-dose clinical lactation study, the concentration of tirzepatide in breast milk was found to be either undetectable or low compared to the maternal administered dose. There are no available data on the effects of tirzepatide on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Mounjaro and any potential adverse effects on the breastfed infant from Mounjaro or from the underlying maternal condition.
Females of Reproductive Potential
Advise females using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation.
Pediatric Use
Adverse reactions reported in pediatric patients 10 years of age and older treated with Mounjaro were similar to those reported in adults with the exception of a higher incidence of vomiting, abdominal pain, and hypoglycemia. The safety and effectiveness of Mounjaro have not been established and use is not recommended in patients less than 10 years of age.
Please see the full Prescribing Information, including Boxed Warning about possible thyroid tumors, including thyroid cancer, and Medication Guide by clicking the links within www.mounjaro.lilly.com/hcp.
Please see Instructions for Use included with the pen.
TR HCP ISI 19DEC2025
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