What are the cardiovascular benefits of Mounjaro (tirzepatide) for diabetes?

From the Guidelines

Mounjaro (tirzepatide) is recommended for people with type 2 diabetes due to its significant cardiovascular benefits, including reducing major adverse cardiovascular events, as evidenced by recent studies 1. The medication, a GLP-1/GIP dual receptor agonist, has been shown to improve several cardiovascular risk factors, such as promoting substantial weight loss, reducing blood pressure, improving cholesterol profiles, and reducing inflammation markers associated with cardiovascular disease. Some of the key benefits of Mounjaro include:

• Reducing major adverse cardiovascular events, including heart attack, stroke, and cardiovascular death
• Promoting substantial weight loss, typically 15-20% of body weight
• Reducing blood pressure, with an average systolic reduction of 5-10 mmHg
• Improving cholesterol profiles by lowering triglycerides and LDL cholesterol while raising HDL cholesterol
• Reducing inflammation markers associated with cardiovascular disease These benefits occur through multiple mechanisms, including improved insulin sensitivity, reduced fat accumulation in the liver and heart, enhanced cardiac function, and beneficial effects on blood vessel health, as noted in recent guidelines 1. Mounjaro is typically started at 2.5 mg weekly by subcutaneous injection, with gradual dose increases up to 15 mg weekly as tolerated, and its cardiovascular benefits appear to increase with longer duration of treatment, with significant improvements observed within 6-12 months of consistent use 1. It is essential to prioritize the use of GLP-1 RAs with demonstrated cardiovascular benefits, such as Mounjaro, in people with type 2 diabetes and established ASCVD or multiple risk factors for ASCVD, as recommended by recent guidelines 1.

From the Research

Cardiovascular Benefits of Mounjaro for Diabetes

• The studies 2, 3, 4, 5, 6 provide information on the effects of tirzepatide (Mounjaro) on cardiovascular events in patients with type 2 diabetes.
• According to the study 3, tirzepatide was found to have a low risk of major adverse cardiovascular events, with a hazard ratio < 1.0 vs. pooled comparators for MACE-4 events (nonfatal myocardial infarction, non-fatal stroke, cardiovascular death, and hospital admission for angina).
• The study 3 also reported that tirzepatide tended to reduce MACE-4 events over a 2-year period, although the number of events was low.
• Another study 4 mentioned that the cardiovascular protection of tirzepatide is being tested in the SURPASS-CVOT trial.
• The study 6 stated that Eli Lilly is developing tirzepatide for the treatment of cardiovascular disorders in type 2 diabetes mellitus, among other indications.

Mechanism of Action and Efficacy

• Tirzepatide is a dual GIP/GLP-1 receptor co-agonist that has been shown to improve glycaemic control and reduce body weight in patients with type 2 diabetes 2, 3, 4, 5.
• The study 3 reported that tirzepatide was more effective in reducing HbA1c and body weight than the selective GLP-1 RA semaglutide and titrated basal insulin.
• The mechanism of action of tirzepatide involves the activation of GIP and GLP-1 receptors, which are key mediators of insulin secretion and food intake regulation 3, 6.

Safety and Tolerability

• The studies 2, 3, 4, 5, 6 reported that tirzepatide was generally well tolerated, with a safety profile consistent with that of GLP-1 receptor agonists.
• The most common adverse events associated with tirzepatide were gastrointestinal events, including nausea, diarrhea, decreased appetite, and vomiting 2, 3, 4.