Tirzepatide gets a big win in obesity-related heart failure

Eli Lilly's tirzepatide has been shown to significantly cut cardiovascular risks in patients with obesity and a form of heart failure with few treatment options, in another big win for the GLP-1 receptor agonist class.

The results from the SUMMIT trial of tirzepatide in obese patients with heart failure with preserved ejection fraction (HFpEF) showed that Lilly's drug cut the risk of cardiovascular mortality and worsening heart failure events by 38% over a median follow-up of roughly two years.

The data – presented at the American Heart Association (AHA) congress in Chicago over the weekend and simultaneously published in the New England Journal of Medicine – also showed that treatment with the dual GLP-1 and GIP agonist alleviated heart failure symptoms, like shortness of breath and fatigue.

Discussing the results, lead SUMMIT investigator Milton Packer of Baylor University Medical Centre in Dallas, noted that HFpEF is the most common form of heart failure and is closely linked to obesity, which is becoming an epidemic in the US and worldwide.

"Obesity contributes to worsening heart failure, and while tirzepatide causes considerable weight loss, research is lacking on its effects on cardiovascular outcomes," said Packer. "This is the first trial that tested the effect of any medication on major heart failure outcomes in patients with HFpEF and obesity."

Lilly said it has already started submitting the SUMMIT data to regulators in the hope of extending the labelling for tirzepatide, which it sells as Mounjaro for type 2 diabetes and Zepbound for obesity.

Approval would help the company in its head-to-head market battle with main rival Novo Nordisk in the GLP-1 category, whose semaglutide is already approved for cardiovascular risk reduction in adults with type 2 diabetes and overweight/obesity with established heart disease, and also showed a benefit in heart failure in the STEP-HFpEF trial.

Novo Nordisk recently pulled its FDA application for semaglutide as a HFpEF treatment in order to compile additional follow-up data, and has said it expects to refile early in 2025.

Data on hard outcomes like cardiovascular risk reduction is expected to unlock reimbursement coverage for GLP-1 drugs, with some insurers reluctant to cover them simply for weight loss.

In the 731-patient SUMMIT study, participants were randomly assigned to either tirzepatide at a dose of between 2.5mg and 15mg per week or placebo, on top of their current heart failure treatment.

After a median follow-up of two years and a maximum of three years, cardiovascular death or worsening heart failure events occurred in 9.9% of the tirzepatide group and 15.3% of those taking placebo.

Most of the benefit came from reduced risk of hospitalisation for heart failure, which fell 56% with Lilly's drug.

Meanwhile, tirzepatide-treated patients saw their weight reduce by around 12% compared to the placebo group, and they had an average 6.9-point improvement over control on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), which measures symptoms.

They also improved their six-minute walking distance test at one year by an average of 18.3 metres compared to placebo.