The Exposure
Tirzepatide is the world's best-selling drug. Yet about $69B of value from its 2025 US patient cohort is exposed over the next five years — to the patients who simply stop refilling.
The Gap
SURMOUNT-1 saw 15% discontinuation. Real-world cohorts run near 50% within a year. The trial measures 72 weeks and the real-world bars 6–12 months — so the true gap is wider, not narrower.
The Gap
Retention falls fast: 86% still on therapy at twelve months in-trial, 54% in real-world diabetes, just 35% in obesity.
The Gap
Obesity loses 51 points against the trial; diabetes loses 32. And the franchise mix is tilting toward obesity — so the economics get worse, not better. (Beyond 12 months is extrapolated.)
The Cause
Among obesity patients who discontinued at the Cleveland Clinic, one reason towers over the rest: cost and insurance, at 47.6%.
The Cause
Only about 16% is the drug itself — side effects or disappointing loss. The rest is access, affordability, and supply. This is a commercial problem before it's a clinical one.
The Cause
Stated at the point of quitting, cost is 47.6%. Mined from clinical notes, it's ~13%. How you measure decides what you see — both are real.
The Unit
The unit that matters is a filled 28-day prescription: about $460 of net revenue, $189 of operating profit. A persistent year is roughly thirteen of them.
The Unit
Thirteen fills make ~$5,980 in net revenue per persistent patient-year. The engine isn't the first script; it's the refill sequence. (Net price is falling — down 13% year-over-year.)
The Model
Take two published points — 84.9% still on at 18 months in-trial, 35% at 13 months in the real world — and let exponential decay connect them.
The Model
Sum the months under each curve: about 49 patient-months in the trial world, 12 in the real one. At $460 a fill, that's $22.5K of lifetime value versus $5.5K.
The Gap, in Dollars
The naive gap is $17K per obesity patient. But a third restart within a year (−$1.3K), and some switch within the portfolio (−$1.5K). The honest closeable gap is about $14K.
The Scale
Weight the gap across indications (~$12.5K), multiply by ~5.5M US patients, and the exposure is ~$69B in revenue — about $28B in operating profit.
The Scale
Only $24–35B is Lilly-addressable. Affordability, copay, fulfillment, titration — those it owns. Prior authorization, formularies, Medicare obesity coverage — those belong to PBMs, payers, and CMS.
The Range
Captured value swings with how much of the gap closes and where net price settles — from under $6B to the mid-$30Bs. The direction is robust; the precision is not.
The Inversion
Six honest counter-arguments: price decline could swamp the gains; reinitiation may already recapture the leak; acquisition still drives growth today. Persistence matters — it isn't the only thing that does.
The Answer
Closing the gap isn't one fix; it's coordinated infrastructure across access, affordability, fulfillment, and engagement — and Lilly owns some levers and only influences others.
The battle moves from acquisition → persistence.
~50% of real-world tirzepatide patients quit within a year. Trial-controlled discontinuation is ~15%.
Cost, coverage churn and refill failures drive most of the leak — well above side-effect intolerance.
Of the ~$69B exposure, only $24–35B is Lilly-addressable. PBMs, payers and CMS hold the rest.
The winners will treat adherence as commercial infrastructure — and be honest about what they own versus what they only influence.