What are the indications for Mounjaro (tirzepatide) in adults with type 2 diabetes?

Mounjaro (Tirzepatide) Indications

Mounjaro is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 1, 2

Primary FDA-Approved Indication

• Glycemic control in type 2 diabetes: Tirzepatide is indicated for adults with type 2 diabetes as adjunctive therapy to diet and exercise for improving blood glucose control 1, 2, 3

Clinical Scenarios Where Tirzepatide Should Be Prioritized

Patients Requiring Substantial Glycemic Reduction

• Consider tirzepatide when target HbA1c is not achieved with current therapy, particularly when substantial reduction is needed (tirzepatide reduces HbA1c by 1.87-2.59%) 4, 5
• Tirzepatide can be considered as first-line treatment beyond metformin for newly diagnosed type 2 diabetes patients requiring medication 4

Patients with Obesity or Overweight

• Prioritize tirzepatide for patients with type 2 diabetes who need significant weight loss, as it produces mean weight reduction of 8.47 kg, with up to 67% of patients achieving ≥10% weight reduction 4, 5
• This weight loss benefit exceeds that of GLP-1 receptor agonists like semaglutide 1 mg 5

Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• Tirzepatide is preferred for glycemic management in patients with MASLD or high risk for liver fibrosis, as it reduces hepatic steatosis 6, 4
• The American Diabetes Association recommends dual GIP/GLP-1 receptor agonists (tirzepatide) for patients with type 2 diabetes, MASLD, and overweight/obesity 6

Patients Requiring Low Hypoglycemia Risk

• Tirzepatide carries low risk of severe hypoglycemia when used as monotherapy or with metformin (risk increases substantially only when combined with insulin or sulfonylureas) 4, 1
• When adding tirzepatide to existing insulin or sulfonylurea therapy, reduce doses of these medications to minimize hypoglycemia risk 4

Positioning in Treatment Algorithm

As Alternative to Insulin

• Tirzepatide is preferred over insulin in adults with type 2 diabetes without evidence of insulin deficiency 6
• If insulin is already being used, combination therapy with tirzepatide is recommended for greater glycemic effectiveness and beneficial effects on weight and hypoglycemia risk 6

Comparison to Other Incretin-Based Therapies

• Tirzepatide demonstrated superior glycemic control and weight loss compared to GLP-1 receptor agonists (dulaglutide 0.75 mg and semaglutide 1 mg) in head-to-head trials 1, 5
• Unlike DPP-4 inhibitors (which should not be added to metformin per ACP guidelines), tirzepatide provides meaningful clinical benefits 6

Important Safety Considerations

Cardiovascular Safety

• Tirzepatide showed no increased risk of major adverse cardiovascular events in pooled analyses 4
• Serious adverse events occurred less frequently with tirzepatide compared to insulin (RR 0.79) 4

Gastrointestinal Effects

• Most common adverse events are gastrointestinal (nausea, diarrhea, decreased appetite, vomiting), typically mild to moderate in severity 1
• Delayed gastric emptying is a class effect that may persist with chronic use 4

Dosing Adjustments

• When initiating tirzepatide in patients on insulin or sulfonylureas, reassess and reduce doses of these medications to minimize hypoglycemia risk 4
• Available as 5 mg, 10 mg, and 15 mg once-weekly subcutaneous injections 1, 5

Clinical Context

While tirzepatide is only FDA-approved for type 2 diabetes, it is under investigation for obesity, cardiovascular disorders, heart failure, non-alcoholic steatohepatitis, and obstructive sleep apnea 2. The current evidence base from SURPASS 1-5 trials demonstrates marked reductions in cardiometabolic risk parameters including blood pressure, visceral adiposity, and triglycerides 5.