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Tirzepatide’s early obesity success gave Lilly a way out of the LOE cycle
Tirzepatide (Mounjaro and Zepbound) gave Eli Lilly a way out of the cycle that traps most big pharma companies: racing to replace revenue lost to a looming loss of exclusivity (LOE). Most of the drug’s potential came from one indication, obesity, early in its patent life; in January 2025, when Sleuth published this analysis, consensus expected tirzepatide to top $70 billion in annual sales by 2030, with about 12 years of patent life still left. Durable mega-blockbusters such as Keytruda and Humira, by contrast, unlocked their revenue slowly over years of new indications.
Other blockbusters unlocked slowly or were one-off markets
Sleuth’s January 2025 chart lines up annual revenue by each drug’s year on the market. Keytruda climbs toward about $30 billion by year 15, partly on forecast, with 49 FDA approvals by year 11 in the chart’s count, and Humira reached about $18 billion by year 15 on 11 approvals. Comirnaty, the COVID-19 vaccine, was a bolus market: about $37 billion in each of its first two years, then about $5 billion by year 4. Tirzepatide had three approvals by year 3, in type 2 diabetes, obesity and obstructive sleep apnea, and the chart’s forecast puts it at about $73 billion in year 9 (2030) and above $100 billion by year 15.
That 2030 figure would be more than twice Keytruda’s size in the chart and nearly double Comirnaty’s pandemic peak. After this analysis, tirzepatide overtook Keytruda: Mounjaro and Zepbound generated $36.5 billion combined in 2025, against $31.7 billion for Keytruda.
The difference is timing. Keytruda and Humira reached their scale deep into their patent lives, while tirzepatide’s was visible within three years of launch.
Operating leverage lets Lilly fund R&D without chasing revenue
Diabetes, sleep apnea, cardiovascular risk and chronic kidney disease support the $70 billion forecast, but most of it rests on the expectation that Lilly will dominate obesity. In Sleuth’s view, the supplementary indications’ biggest contribution may be easing payer reimbursement. Positive Alzheimer’s data for the GLP-1 class would have raised the ceiling, but Novo Nordisk’s EVOKE and EVOKE+ trials of oral semaglutide missed their primary endpoints in November 2025.
In January 2025, consensus also had Lilly’s total revenue passing $100 billion by 2030 and operating margins rising above 50% by 2029, from about 32% in 2024, so Lilly can lead the industry in absolute R&D spend while improving its margins. It will keep investing in next-generation obesity assets, but it does not need anything like the more than 1,000 pembrolizumab studies behind Keytruda to unlock tirzepatide’s potential.
A long runway changes how Lilly can use R&D and BD
Sleuth’s January 2025 argument named three consequences:
- Higher-risk, longer-term R&D. More than a decade of visible growth lets Lilly focus on what its portfolio will look like in 2035 and beyond.
- No need to buy near-term revenue. Lilly does not have to rush into acquisitions to bolster revenue or chase what is popular, unlike peers facing large near-term LOEs, with BMS and Merck among the most exposed.
- Creative BD structures. Lilly’s $500 million Biotech Ecosystem Venture Fund with Andreessen Horowitz, announced in January 2025, is one example.
In 2026 through early September, Lilly announced 13 of the 29 buyouts by the top 15 pharma companies, according to Sleuth’s T15 pharma buyout map, in a year when most of those acquisitions were early-stage bets rather than bought revenue.
Sleuth’s January 2025 view was that when tirzepatide’s LOE arrives, Lilly will have had more than a decade to soften it by moving patients to next-generation obesity drugs and building a broad early-stage pipeline.
Forecasts, consensus figures and approval counts are as of January 2025; chart revenue is shown by year on the market. This page is a dated snapshot of Sleuth’s argument, with later sales, trial and deal updates current as of September 2026.
Frequently asked questions about Eli Lilly and tirzepatide
How big was tirzepatide expected to become?
In January 2025, consensus expected tirzepatide (Mounjaro and Zepbound) to top $70 billion in annual sales by 2030, with about 12 years of patent life left. In 2025 it generated $36.5 billion, ahead of Keytruda’s $31.7 billion.
Why is Lilly’s position different from other big pharma companies?
Keytruda and Humira built revenue slowly through many approvals, while tirzepatide’s scale came early from one indication. In Sleuth’s January 2025 view, that lets Lilly fund longer-term R&D and creative BD instead of buying revenue to replace LOEs.
What is the Lilly and Andreessen Horowitz venture fund?
A $500 million Biotech Ecosystem Venture Fund that Lilly and Andreessen Horowitz (a16z) announced in January 2025. Sleuth cited it as an example of the creative BD structures that tirzepatide’s long runway makes possible.
