Eli Lilly on Thursday released late-stage data showing a 38% reduction in the risk of heart failure outcomes, as it plays catch-up with Novo Nordisk’s semaglutide which won the FDA’s cardio nod in March.
Eli Lilly’s blockbuster weight-loss treatment tirzepatide aced the Phase III SUMMIT study, demonstrating significant therapeutic benefit in patients with heart failure with preserved ejection fraction, according to a topline readout on Thursday.
At a median follow-up of 104 weeks, patients treated with tirzepatide versus placebo saw a 38% drop in the relative risk of heart failure outcomes, as quantified by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. The treatment effect was statistically significant, with a p-value of 0.026, according to Lilly.
SUMMIT defined heart failure outcomes as a composite of cardiovascular death and urgent healthcare visits and hospitalizations related to heart failure, as well as the intensification of oral diuretic medication.
Tirzepatide also met SUMMIT’s key secondary endpoints, leading to an improvement in exercise capacity and a reduction in the inflammatory marker high-sensitivity C-reactive protein. Mean body weight declined through 52 weeks of treatment, with tirzepatide-treated patients losing 15.7% of their body weight compared to 2.2% in the placebo group.
SUMMIT is a randomized, double-blinded, parallel and placebo-controlled study that assessed three doses of tirzepatide—5 mg, 10 mg and 15 mg. The trial enrolled more than 730 obese adults with heart failure with preserved ejection fraction (HFpEF), with or without type 2 diabetes. In addition to efficacy, SUMMIT also evaluated the safety and tolerability of tirzepatide in this indication.
The most commonly reported side effects in SUMMIT were related to the gastrointestinal system—such as nausea, vomiting, constipation and diarrhea—though most were mild or moderate in severity. The study found no new signals of concern. Tirzepatide’s safety profile was consistent with what previous studies have found.
Jeff Emmick, senior vice president of product development at Lilly, in a statement called SUMMIT a “first-of-its-kind trial” showing that tirzepatide “reduced severity of symptoms and improved heart failure outcomes” in HFpEF patients with obesity. Previous studies on incretin-based treatments “focused on symptoms and physical limitations,” according to Emmick.
Lilly will continue its analysis of SUMMIT’s findings, which it plans to present at an upcoming scientific conference and submit to a peer-reviewed journal. The pharma will also share these results with the FDA to seek a cardiovascular approval for tirzepatide “starting later this year,” according to its announcement.
Wednesday’s results come as Lilly plays catch-up with Novo Nordisk, whose blockbuster GLP-1 therapy Wegovy (semaglutide) won the FDA’s nod in March 2024 to reduce the risk of cardiovascular death, heart attack and stroke in obese or overweight adults with cardiovascular diseases.
Novo is also studying the potential of semaglutide in renal diseases. In March 2024, the Danish drugmaker released findings from the Phase III FLOW study, touting a 24% reduction in the risk of kidney disease progression, major adverse cardiovascular events and kidney death in type 2 diabetes patients with chronic kidney disease.
Meanwhile, Lilly is trying to expand tirzepatide into metabolic dysfunction-associated steatohepatitis (MASH) and sleep apnea. The pharma posted Phase II data in June 2024, demonstrating the absence of MASH without fibrosis worsening in at least 50% of patients. That same month, Lilly unveiled findings from the Phase III SURMOUNT-OSA program, which showed that tirzepatide could cut the apnea-hypopnea index by up to nearly 63%.
