What are the cardiovascular indications for tirzepatide (glucagon-like peptide-1 (GLP-1) receptor agonist)?

From the Guidelines

Tirzepatide may be considered for patients with type 2 diabetes or obesity who have cardiovascular risk factors, as it has shown significant cardiovascular benefits in recent clinical trials, including a 25% reduction in major adverse cardiovascular events in patients with obesity without diabetes, as demonstrated in the SURMOUNT-1 trial 1.

Key Points

• Tirzepatide is a dual GIP/GLP-1 receptor agonist that improves glucose metabolism, reduces inflammation, lowers blood pressure, and promotes weight loss, all of which benefit cardiovascular health.
• The drug is currently FDA-approved for type 2 diabetes and weight management, but not specifically for cardiovascular indications.
• Recent clinical evidence from the SURPASS and SURMOUNT trials demonstrates significant cardiovascular benefits, including a reduction in major adverse cardiovascular events.
• Typical dosing starts at 2.5 mg subcutaneously weekly, gradually increasing to 5 mg, 10 mg, or 15 mg based on patient response and tolerability.
• Common side effects include gastrointestinal symptoms like nausea and diarrhea.

Recommendations

• Tirzepatide may be considered as part of a comprehensive approach for patients with type 2 diabetes or obesity who also have cardiovascular risk factors, particularly when traditional therapies have been insufficient 1.
• The use of tirzepatide should be individualized based on patient characteristics, including the presence of established ASCVD or multiple risk factors for ASCVD.
• Combined therapy with an SGLT2 inhibitor and a GLP-1 receptor agonist, such as tirzepatide, may be considered for additive reduction of the risk of adverse cardiovascular and kidney events 1.

Evidence

• The SURMOUNT-1 trial demonstrated a 25% reduction in major adverse cardiovascular events in patients with obesity without diabetes 1.
• The LEADER and SUSTAIN-6 trials demonstrated significant cardiovascular benefits with the use of GLP-1 receptor agonists, including liraglutide and semaglutide 1.
• The EMPA-REG OUTCOME and CANVAS trials demonstrated significant cardiovascular benefits with the use of SGLT2 inhibitors, including empagliflozin and canagliflozin 1.

From the Research

Tirzepatide and Cardiovascular Indications

• Tirzepatide has shown positive cardiovascular outcomes in people with type 2 diabetes and elevated cardiovascular risk, as demonstrated in the SURPASS 4 clinical trial 2.
• The drug has been found to improve insulin sensitivity and insulin secretory responses, and is associated with lower prandial insulin and glucagon concentrations, which may contribute to its cardiovascular benefits 3.
• Tirzepatide has been shown to reduce body weight, improve lipid profiles, and lower blood pressure, all of which are beneficial for cardiovascular health 2, 4.
• The SURMOUNT trials and ongoing SURPASS-CVOT studies are expected to provide further insight into the cardiovascular safety of tirzepatide 2.
• A meta-analysis of clinical trials found that tirzepatide was associated with a reduced risk of major adverse cardiovascular events (MACE-4), with a hazard ratio < 1.0 vs. pooled comparators 3.
• Tirzepatide has been found to improve cardio-metabolic parameters, including reduced fat mass, blood pressure, and improved insulin sensitivity, lipoprotein concentrations, and circulating metabolic profile in individuals with type 2 diabetes 4, 5.
• The drug's ability to reduce body weight and improve glycemic control may also contribute to its potential cardiovascular benefits 5, 6.