When should Mounjaro be started for adults with type 2 diabetes?
[Healthcare Professional]
Hi, my name is Dr. Ebon Bourne. Today we’re going to discuss how Mounjaro, a glucose-dependent insulinotropic polypeptide, or GIP, and glucagon-like peptide-1, or GLP-1, receptor agonist, may fit into the type 2 diabetes treatment journey.
Some healthcare professionals may reserve Mounjaro for adults with type 2 diabetes who have highly elevated glycated hemoglobin, or A1C, and notable excess body weight.
However, Mounjaro has the potential to improve glycemic control at various points in a patient’s type 2 diabetes treatment journey.
Join me as we learn how Mounjaro may help patients achieve their individualized treatment goals, as supported by clinical efficacy and safety results.
First, let’s review the Indication and Boxed Warning for Mounjaro.
Mounjaro is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Mounjaro 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 (MTC), in humans as 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 (MEN 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, 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.
Let’s start by reviewing some recommendations from the American Diabetes Association, or ADA, and the American Association of Clinical Endocrinology, or AACE.
For most adults with type 2 diabetes, ADA recommends an A1C goal of less than 7%, while AACE recommends an A1C goal of 6.5% or less. Individualized treatment plans aimed at achieving these glycemic targets should also consider weight management goals.
To achieve and maintain the intended treatment goals, pharmacological strategies that provide sufficient effectiveness should be used, with a focus on achieving glycemic goals as soon as possible.
In many patients with type 2 diabetes, a stepwise approach may not lead to sustained glycemic control. However, a proactive approach to type 2 diabetes treatment from initial diagnosis is consistent with guideline recommendations to regularly reassess patients and may help patients reach their glycemic goals.
Mounjaro is one treatment option that can be considered to improve glycemic control in adults with type 2 diabetes. Let’s learn more about the supporting clinical data.
In SURPASS-2, Mounjaro was studied head-to-head versus Ozempic® 1 milligram in adults with type 2 diabetes who had inadequate glycemic control on stable doses of metformin.
In this population, the mean baseline A1C was 8.3%, the mean duration of type 2 diabetes was 8.6 years, and the mean baseline body mass index, or BMI, was 34.2 kilograms per meter squared.
Participants were randomized to receive once-weekly subcutaneous Mounjaro 5, 10, or 15 milligrams or once-weekly subcutaneous Ozempic 1 milligram, all in combination with at least 1500 milligrams of metformin per day.
The primary objective was to demonstrate noninferiority of Mounjaro 10 and/or 15 milligrams to Ozempic 1 milligram in the mean A1C change from baseline at 40 weeks.
The key secondary objectives are also shown here.
For the primary endpoint of mean A1C change from baseline at 40 weeks, A1C reductions with Mounjaro 5, 10, and 15 milligrams ranged from 2 to 2.3%, resulting in final A1Cs of 6 to 6.3%. By comparison, Ozempic 1 milligram reduced A1C by 1.9%, for a final A1C of 6.4%.
For the key secondary endpoint of mean weight change from baseline at 40 weeks, weight reductions for the Mounjaro treatment groups ranged from 8.2 to 11.8%, compared with 6.2% for Ozempic 1 milligram. As a reminder, Mounjaro is not indicated for weight loss.
Mounjaro demonstrated both superior A1C reductions and greater weight reductions across doses versus Ozempic 1 milligram.
Now, let’s review how these results relate to A1C thresholds at 40 weeks. 82 to 86% of patients receiving Mounjaro 5, 10, or 15 milligrams reached an ADA guideline–recommended A1C of less than 7% at 40 weeks, compared to 79% of patients in the Ozempic 1-milligram group.
Significantly more patients achieved the ADA A1C target of less than 7% with the Mounjaro 10- and 15-milligram doses compared with Ozempic 1 milligram.
In addition, 69 to 80% of patients in the Mounjaro groups and 64% of patients in the Ozempic 1-milligram group had an A1C of 6.5% or less at 40 weeks.
I also want to note 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.
Weight management is an important component of type 2 diabetes treatment plans.
In a post hoc analysis, patients with a baseline BMI less than 30 kilograms per meter squared had mean weight reductions that ranged from 7.2 to 10.6% for Mounjaro 5, 10, and 15 milligrams and 6.6% for Ozempic 1 milligram.
For patients with a baseline BMI greater than or equal to 30 kilograms per meter squared, mean weight reductions ranged from 8.6 to 12.3% for the Mounjaro treatment groups and 6.1% for the Ozempic 1-milligram group. As a reminder, Mounjaro is not indicated for weight loss.
Safety results for SURPASS-2 show that the most common adverse events reported in at least 5% of patients in the Mounjaro treatment groups were mostly gastrointestinal in nature. Reports of nausea, diarrhea, and vomiting were most frequent during the dose-escalation period and tended to decrease over time. Overall discontinuation rates as well as discontinuations due to gastrointestinal-related adverse events can also be seen here.
Please note the Select Important Safety Information related to acute kidney injury. Dehydration from gastrointestinal adverse events may cause kidney problems. To learn more, please read the Important Safety Information.
The incidence of hypoglycemia in SURPASS-2 ranged from 0.2 to 1.7% for Mounjaro 5, 10, and 15 milligrams and was 0.4% for Ozempic 1 milligram. The incidence of severe hypoglycemia ranged from 0 to 0.2% for the Mounjaro groups and was 0% for Ozempic 1 milligram.
I hope you enjoyed learning about how Mounjaro may be an appropriate treatment option for your adult patients with type 2 diabetes, with potential to support their individualized treatment goals.
Now I’ll share some information about the efficacy and safety of Mounjaro across the SURPASS phase 3 registrational studies, of which this head-to-head study of Mounjaro versus Ozempic 1 milligram was a part.
The effectiveness of Mounjaro as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes was established in 5 trials. A similar study design was used in each trial. Patients were randomized to receive Mounjaro 5, 10, or 15 milligrams, placebo, or an active comparator.
In trials that allowed background glucose-lowering therapy, various combinations of metformin, SGLT2 inhibitors, sulfonylurea, and titrated insulin glargine were permitted. Comparator treatments included placebo, Ozempic 1 milligram (which we have just reviewed), titrated Tresiba®, and titrated insulin glargine.
The primary endpoint across the SURPASS studies was the mean change in A1C from baseline at 40 or 52 weeks. Mounjaro delivered superior A1C reductions across the range of background therapies and comparators studied.
Similarly, for the key secondary endpoint of mean change in weight from baseline, Mounjaro consistently demonstrated greater weight reductions versus comparators. As a reminder, Mounjaro is not indicated for weight loss.
In the pool of placebo-controlled studies, adverse reactions reported in at least 5% of patients taking Mounjaro included nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain.
Across the placebo-controlled studies, 0% of patients in the Mounjaro treatment groups reported hypoglycemia or severe hypoglycemia and 1% of patients in the placebo group reported hypoglycemia after 40 weeks when it was used as a monotherapy.
When used as an add-on to basal insulin with or without metformin, the incidence of hypoglycemia after 40 weeks for Mounjaro 5, 10, and 15 milligrams ranged from 14 to 19% and was 13% for placebo. The incidence of severe hypoglycemia ranged from 0 to 2% in the Mounjaro groups, with no reported incidents for placebo.
Thank you for taking the time to learn about Mounjaro today.
[Select Important Safety Information]
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 severe abdominal pain sometimes radiating to the back, which may or may not be accompanied by 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, severe gastrointestinal adverse reactions occurred more frequently among patients receiving Mounjaro (5 milligrams 1.3%, 10 milligrams 0.4%, 15 milligrams 1.2%) than placebo (0.9%). 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 clinical trials, acute gallbladder disease was reported by 0.6% of Mounjaro-treated patients and 0% 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
The most common adverse reactions reported in greater than or equal to 5% 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
There are no data on the presence of tirzepatide in human milk, the effects on the breastfed infant, or the effects 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
Safety and effectiveness of Mounjaro have not been established and use is not recommended in pediatric patients.
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.
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