Lilly's Tirzepatide: A Game-Changer for HFpEF Patients with Obesity

In a significant breakthrough for patients with heart failure with preserved ejection fraction (HFpEF) and obesity, Eli Lilly's tirzepatide has demonstrated remarkable results. In the SUMMIT trial, this innovative drug reduced the risk of worsening heart failure events by a staggering 38% compared to placebo. Let's delve into the science behind this groundbreaking medication and its potential impact on the lives of millions of patients worldwide.

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, targets multiple pathways to combat HFpEF and obesity. By activating GIP and GLP-1 receptors, tirzepatide promotes weight loss, improves insulin sensitivity, and reduces inflammation. These actions lead to a decrease in visceral adiposity, sodium retention, and plasma volume expansion, thereby mitigating myocardial injury and fibrosis. Additionally, tirzepatide enhances LV filling and tolerance, ultimately reducing the risk of hospitalizations and cardiovascular mortality.

The SUMMIT trial, presented at the American Heart Association 2024 Scientific Sessions, randomized 731 patients with HFpEF and obesity to receive tirzepatide or placebo. The primary endpoint of cardiovascular death or worsening heart failure events occurred in 36 patients in the tirzepatide group compared with 56 patients in the placebo group, with a hazard ratio of 0.62 (95% CI: 0.41–0.95; p=0.026). Broken down, researchers found that worsening heart failure events were less frequent in the tirzepatide group, but no significant difference was observed in cardiovascular death.

Tirzepatide's weight loss effect significantly contributes to its overall impact on HFpEF symptoms and outcomes. In the SURMOUNT-1 three-year study, weekly tirzepatide injections (pooled 5 mg, 10 mg, 15 mg doses) significantly reduced the risk of progression to type 2 diabetes in adults with pre-diabetes and obesity or overweight, compared with placebo, over 176 weeks. Participants treated with tirzepatide had an average weight reduction of 22.9% (15 mg dose) through the three-year treatment period for the efficacy estimandi.



Tirzepatide's dual GIP and GLP-1 receptor agonism offers long-term benefits by targeting visceral adiposity, a key driver of HFpEF pathophysiology. By reducing sodium retention, plasma volume expansion, and myocardial injury, tirzepatide can decrease LV filling pressure and improve symptoms. However, potential risks include gastrointestinal side effects, which were mild to moderate in severity in SUMMIT. Long-term data on tirzepatide's safety and efficacy in HFpEF patients are still being collected.

In conclusion, Lilly's tirzepatide has emerged as a game-changer for patients with HFpEF and obesity. Its ability to reduce the risk of worsening heart failure events by 38% is a testament to its effectiveness in targeting multiple pathways that contribute to HFpEF. With continued research and long-term data collection, tirzepatide has the potential to revolutionize the treatment landscape for this patient population and improve their quality of life.