Lilly starts first head-to-head weight loss trial of tirzepatide against Wegovy
The first head-to-head obesity trial between the two leading GLP-1 drugs could give patients a direct comparison that separate studies cannot provide.
On April 21, 2023, Eli Lilly registered a phase 3b trial called SURMOUNT-5 that directly compares its drug tirzepatide with semaglutide 2.4 mg for weight loss in adults with obesity — the first head-to-head study of the two medicines [1]. Tirzepatide is sold as Mounjaro, and semaglutide 2.4 mg is sold as Wegovy [1].
The trial aims to enroll 700 participants at 61 sites in the United States, Canada, South America and several European countries, according to its clinicaltrials.gov listing [1]. It was expected to begin on April 28, 2023, run for about 78 weeks, and had an estimated primary completion date in February 2025 [1].
Investigators will compare the percentage of weight lost from baseline after 72 weeks, the study's primary endpoint [1]. Secondary measures include the share of patients who reach certain amounts of weight loss [1]. Lilly has not said whether the study is designed to show that tirzepatide is better than semaglutide or only that it is not worse; the company did not immediately respond to a request for comment [1].
To join, a patient must have a body mass index of at least 30, or at least 27 along with a diagnosis of at least one of four weight-related conditions: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease [1]. Those criteria match the patient population Wegovy is approved for [1].
Until now, the two drugs had been tested only in separate trials. In SURMOUNT-1, tirzepatide produced weight reduction of up to 21% in patients without diabetes [1]. In its own trial, Wegovy produced an average weight loss of 15%, a 12.4 percentage point difference from placebo, in patients without diabetes [1]. Without a head-to-head study, no one could say for certain how Wegovy compares with tirzepatide [1]. Wegovy belongs to the GLP-1 agonist drug class, while tirzepatide is a dual GLP-1/GIP agonist, which theoretically could trigger a stronger weight loss effect [1].
When SURMOUNT-5 was registered, Wegovy had held FDA approval for chronic weight management since 2021, while tirzepatide was approved only to treat type 2 diabetes [1]. Lilly had started a rolling FDA submission for tirzepatide in obesity with a goal to launch later in 2023, and it said it might use a different brand name for the obesity version [1].
Three other Lilly obesity trials were close to reporting at the time: SURMOUNT-2 wrapped up on April 10, 2023, while SURMOUNT-3, which pairs tirzepatide with intensive lifestyle modification, and SURMOUNT-4, which evaluates continued treatment, had both passed their primary completion dates [1]. Lilly was also expanding manufacturing, including a $3.7 billion investment in two ingredient sites in Indiana and $1.7 billion for a diabetes and obesity drug plant in North Carolina [1].
Why it matters for patients
People choosing between these two drugs have had to compare results from separate studies, which cannot settle which medicine works better for a given person. SURMOUNT-5 is the first study designed to answer that question directly in the same group of patients, using the same eligibility rules as Wegovy's approved population [1]. Analysts expected large markets for both drugs, with UBS projecting up to $25 billion in peak sales for tirzepatide and other analysts putting it at or below $10 billion, while Cowen estimated the global obesity drug market could reach $30 billion by 2030 and an earlier Morgan Stanley estimate put it at $50 billion [1]. Demand has also outpaced supply before: both drugs went into shortage for months before the companies recently resolved those shortages [1]. How insurers would cover tirzepatide for weight loss has not been reported.
What happens next
Results from SURMOUNT-2 were expected soon after the SURMOUNT-5 registration, and SURMOUNT-3 and SURMOUNT-4 had already passed their primary completion dates, though their listings had not yet shown completion [1]. SURMOUNT-5's own primary completion was estimated for February 2025 [1]. Outcome data from the head-to-head study had not been reported.
Sources
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