Tirzepatide shows substantial reductions in weight and waist circumference reductions in a comparison trial with semaglutide.
Tirzepatide (Mounjaro, Eli Lilly) may surpass semaglutide (Wegovy, Novo Nordisk) for weight loss in patients with obesity and no diabetes, according to new research in the NEJM.
The phase 3b study randomly assigned 751 adults with obesity but without diabetes to receive either tirzepatide (10mg or 15mg) or semaglutide (1.7mg or 2.4mg) subcutaneously weekly for 72 weeks. Patients were given the maximum tolerated dose of the medication.
The study, which was sponsored by Eli Lilly, found that patients on tirzepatide lost 20.2% of their body weight over the study period on average, compared with 13.7% in the semaglutide group. This equated to 22.8kgs and 15kg, respectively.
Almost 65% of patients in the tirzepatide group lost 15% of their body weight, compared with 40% of the semaglutide group. Similarly, waist circumference shrunk by 18.4cm in the tirzepatide group compared with 13cm in the semaglutide group, on average.
Patients in the tirzepatide group were more likely than those in the semaglutide group to lose 10%, 15%, 20% and 25% of their weight, the study found.
“With both treatments in our trial, as weight reduction increased, greater improvements occurred in cardiometabolic risk factors, including blood pressure, glycemia and lipid levels,” the authors wrote in NEJM.
Dr Ted Wu, endocrinologist and director of the Diabetes Centre at the Royal Prince Alfred Hospital in Sydney, emphasised that both drugs were highly effective.
“We are seeing levels of weight loss that we could only barely imagine five years ago – so it’s not as if there’s a dud between these two,” he said.
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This study offered new insights into the efficacy of both drugs at higher doses, he said.
In particular, he noted that patients in the tirzepatide group were twice as likely to lose 25% of their initial body weight (32% vs 16%) – which was the weight loss expected after bariatric surgery.
This study also added to the body of research that suggested nausea and vomiting were independent of weight loss, he said.
While tirzepatide was associated with a greater weight loss, patients appeared to experience fewer side effects. Most side effects were mild to moderate and gastrointestinal, and happened as patients were escalating their dose.
Around three in four patients overall experienced side effects, and gastrointestinal side effects led to discontinuation in 2.7% of the tirzepatide group and 5.6% of the semaglutide group. Patients in the tirzepatide group were more likely to have injection-site reactions though (8.6% vs 0.3%), and serious adverse effects were similar in both groups (4.8% vs 3.5%).
According to a statement from Eli Lilly, the company expected the findings to be considered by PBAC “as it responds to a request from the Federal Minister for Health and Aged Care for advice on a path to equitable access to obesity management therapies”.
It also said supply had increased dramatically thanks to investments in manufacturing globally.
Dr Wu said the cost and availability of these medications would play a role in which one patients should take.
He said he expected PBAC to take a staged approach to the introduction of these agents for obesity, if it did approve the medications at all.
“These are two great options, and people can have different side effect profiles on different medications. And it actually does come down to patient preference,” Dr Wu said.
Dr Wu has been on advisory boards and been a speaker at events for both Eli Lilly, Novo Nordisk, as well as a number of other pharmaceutical companies.
A spokeswoman for Novo Nordisk said semaglutide had “robust data” supporting its benefits.
“In combination with diet and exercise, Wegovy (semaglutide) is the only obesity medicine indicated to reduce the risk of major cardiovascular events such as death, heart attack, or stroke in adults with known heart disease and with either obesity or overweight and without Type 1 or Type 2 diabetes,” she said.
“These significant CV events were assessed regardless of change in weight in the landmark SELECT trial.”
“Semaglutide has a cumulative exposure of over 33 million patient-years since 2018.”
This article has been updated to include comments from Novo Nordisk.
