The myth-busts, hot takes, explainers, and tools worth keeping.
⚡Myth Buster· 1
⚡Myth Buster2:01:00
Why Big Pharma Avoided Weight-Loss Drugs for Decades
A history of failed and dangerous weight-loss drugs, from amphetamines to fen-phen, explains why the industry and even Novo Nordisk itself long dismissed obesity treatment.
Fen-phen's 1990s heart damage scandal scared pharma away from weight-loss R&D for decades
As recently as 2005 Novo Nordisk's own CEO said obesity was a social problem, not a drug opportunity
A roughly 10% body weight loss threshold was seen as the minimum needed for a commercially viable drug
“obesity is primarily a social and cultural problem it should be solved by means of a radical restructuring of society there is no business for…”
“researchers thought it was actually impossible to create a weight loss drug that was both safe and effective”
#obesity stigma#fen-phen#weight loss drug history
◆Hot Take· 1
◆Hot Take3:26:00
Is Pharma Actually the Villain of Healthcare?
Ben and David argue that pharma companies, despite their reputation, are the only part of the healthcare value chain actually taking innovation risk, while insurers and PBMs post suspiciously stable profits.
Pharma is only about 13.3% of total US healthcare revenue
Pharma net income is volatile, reflecting real R&D risk, while insurer profits stay flat even through crises like COVID
Health insurance in the US functions more like guaranteed access than true risk-bearing insurance
“Pharma as a whole of the medical pie only occupies about 133% of Revenue”
“health insurance in the US is not insurance it's access it's 100% right”
#healthcare economics#pharma reputation#insurance industry
✶Explainer· 3
✶Explainer34:00
Why a Charitable Foundation Controls Europe's Largest Company
The unique Danish foundation-controlled ownership structure set up in 1924 still governs Novo Nordisk today and holds the world's largest charitable endowment.
Nordisk Insulin was set up as an operating company 100% owned by a foundation
The foundation's dual mission: sell insulin at cost in Scandinavia, profit from exports to fund research
The foundation still controls 77% of voting shares and holds a $120B endowment, the largest charitable foundation in the world
“this operating company is 100% owned and controlled by a foundation that they also set up”
#corporate structure#foundation ownership#Denmark
✶Explainer2:15:00
Semaglutide: Twice as Effective and Once-a-Week
Semaglutide's longer half-life and doubled efficacy versus liraglutide turned GLP-1s from a niche diabetes drug into the cultural phenomena Ozempic and Wegovy.
Semaglutide only needs weekly injection versus daily for liraglutide
It roughly doubles weight loss efficacy to 15%+ long-term BMI reduction
Ozempic (diabetes) and Wegovy (weight loss) are the same molecule, marketed under different names
“it is twice as effective as L glutide for weight loss so we're talking 15% plus long-term BMI reduction”
#semaglutide#Ozempic#Wegovy
✶Explainer1:26:00
Untangling the US Drug Pricing Maze: PBMs and Rebates
A breakdown of how manufacturers, distributors, pharmacies, PBMs, and insurers interact to set the real price of a drug in America.
Three PBMs (Express Scripts, CVS Caremark, OptumRx) control about 80% of the US market
Manufacturers pay rebates off list price, but net prices are opaque to consumers
Eli Lilly has publicly said rebates account for roughly 75% of insulin's sticker price
“my favorite quote from one source that we talked to described rebates as a uh game of hide the sausage”
“there's essentially three that cover about 80% of the market and those are Express Scripts CVS KARK and optim RX”
#PBM#drug pricing#US healthcare system
❝Story· 9
❝Story05:30
The 1921 Toronto Discovery That Started It All
Banting, Best, and McLeod isolate insulin at the University of Toronto, transforming type 1 diabetes from a death sentence into a manageable disease.
Frederick Banting, Charles Best, and John McLeod extracted insulin from dog pancreases in 1921
Before insulin, the only 'treatment' for diabetes was the starvation diet
Banting and McLeod won the 1923 Nobel Prize, controversially excluding Best
“it was literally called the starvation diet and it was just attempt to prolong your life as long as possible but like you are going…”
“two years later when the Nobel committee Awards them the 1923 Nobel Prize in physiology or medicine for the discovery of insulin it is Banting…”
#insulin history#diabetes#Nobel Prize#Toronto
❝Story18:30
How a Nobel Laureate's Wife's Diagnosis Founded Nordisk
August Krogh's wife Marie is diagnosed with diabetes, sending him to Toronto and setting off the chain of events that becomes Nordisk.
Marie Krogh, one of Denmark's first female physicians, self-diagnoses diabetes in 1920
August Krogh had nominated Banting and McLeod for the Nobel Prize
The Kroghs' trip to Toronto secured Scandinavian rights to produce insulin
“in 1920 the same summer that he wins the Nobel Prize his wife Marie Crow is diagnosed with diabetes”
#Novo Nordisk history#August Krogh#founding story
❝Story39:30
The Bitter Sibling Rivalry: How Novo Was Born From a Firing
Two brothers fired from Nordisk storm out and found rival company Novo, kicking off 65 years of fierce head-to-head competition.
Harold and Thorvald Petersen were early Nordisk employees who clashed with Hagedorn
Thorvald was fired, Harold resigned in solidarity, and they founded Novo down the street
The rivalry drove decades of competing insulin innovation until the 1989 merger
“we will show you and they storm out of the building and go down the street and they found a new insulin company a Novo…”
“for the next 65 years these two companies would compete in Blood Sport head-to-head hated each other”
#rivalry#company founding#competition
❝Story52:00
World War II Splits Novo and Nordisk's Fortunes
Nazi occupation of Denmark freezes Nordisk's export revenue while Novo becomes the sanctioned insulin supplier for occupied Europe.
Nordisk's licensing revenue from Allied countries collapsed overnight under occupation
Novo was directed by Germany to massively expand production for occupied Europe
After the war, Denmark required Novo and the Petersens to repay wartime profits
“they are now essentially the official Nazi sanctioned insulin provider for all of Nazi occupied Europe”
#World War II#insulin history#business ethics
❝Story1:14:30
Genentech, Eli Lilly, and the Race for Human Insulin
Genentech's 1980 recombinant DNA breakthrough with Eli Lilly creates the first genetically engineered drug and triggers a biotech investing frenzy, while Novo's rushed response flops.
The first genetically engineered drug ever produced was human insulin
Novo rushed out a chemically modified pig insulin as a stopgap, which was a commercial flop
Nordisk's patient wait-and-see approach let it pass Hoechst to become the #3 global insulin player by 1984
“in 1984 Nordisk passes the German company H to become the number three Global player in insulin”
#Genentech#biotech history#human insulin
❝Story1:32:00
1989: Bitter Rivals Novo and Nordisk Finally Merge
After a decade of on-and-off talks, Novo and Nordisk merge their operating companies and foundations in a 62/38 split, forming Novo Nordisk.
The merger combined roughly $1B in insulin revenue and 50% global market share
Management believed the combined company would still eventually need to merge with a larger pharma giant
That expected further merger never happened thanks to unanticipated organic growth
“in January 1989 the Novo Nordisk merger is finally announced and it's a dual merger of both the operating companies and their respective foundations”
#merger#company history
❝Story1:37:30
When the Foundation Board Said No to a Sale
In 2004 Novo Nordisk management had a deal to merge with Serono, but the foundation board rejected it, a decision that preserved the independent company that would later develop Ozempic.
Management and the operating board were aligned to sell, but foundation approval was required
The foundation board twice rejected management's business case in 2004
In hindsight this decision was essential to Novo Nordisk's later independent GLP-1 success
“so they go to the foundation board expecting that everybody's going to see the light and just agree here and the foundation board is like…”
“100% chance if this ownership structure were not in place we would not be doing this episode today”
A scientist's persistence against an internal ultimatum leads to liraglutide, the breakthrough molecule that would eventually lead to Ozempic.
Natural GLP-1 only stays active in the body for about 5 minutes, stumping the industry
Knudsen faced a company ultimatum to produce a viable drug candidate within a year or the program would be shut down
She grafted a fatty acid onto GLP-1 to extend its half-life to 13 hours, creating liraglutide
“management actually gives her an ultimatum and they're like you either need to crack this and get an actual drug candidate in the pipeline within…”
#GLP-1#drug discovery#scientific persistence
❝Story1:51:30
The Poisonous Lizard That Also Led to a GLP-1 Drug
Completely independent of Novo's research, American researchers discovered a GLP-1 analog in Gila monster venom, leading to Eli Lilly's Byetta.
Researchers at the VA and University of Toronto identified a GLP-1-like hormone in Gila monster venom
This became Byetta, the first GLP-1 drug ever approved, in 2005
Byetta required two daily injections, limiting its adoption compared to later drugs
“a hormone contained in the Venom of the Gila monster lizard literally the lizard called The Gila monster which has poisonous venom one of the…”
#parallel discovery#Byetta#drug history
▲Takeaway· 1
▲Takeaway2:41:00
How Insulin Stopped Being a Great Business
Regulatory price caps, biosimilar competition, and GLP-1 cannibalization converged to destroy insulin's once-durable profitability just as Novo Nordisk's growth shifted to GLP-1s.
US officials alleged 600%+ insulin price increases from 2001-2019 in lockstep among competitors
Biosimilar insulin arbitraged away much of the remaining margin
GLP-1 drugs reduce demand for insulin, further squeezing the category
“us officials alleged that Novo Nordisk increased prices more than 600% between 2001 and 2019 in lock step with competitors to the detriment of diabetics”