Show Notes
GLP-1 drugs like Ozempic and Mounjaro have transformed the treatment of obesity as well as diabetes, help treat heart disease, kidney disease, sleep apnea, and maybe even Alzheimer’s. But they are far from the only medicine with more than one use. Aspirin, colchicine, minoxidil, and Viagra were all found to treat more conditions than expected, and about a third of drugs end up with a second approved use. In this episode, Jacob and Saloni explore the idea of drug repurposing: taking a medicine made for one disease and finding it works against others. They trace how GLP-1 drugs emerged from an adorable Gila monster, why some drugs have multiple uses, why so many of those uses go untested, and how patents, competition, prizes, and platform trials shape whether we ever find them. Hard Drugs is a podcast from Works in Progress about medical innovation presented by Saloni Dattani and Jacob Trefethen.
You can watch or listen on YouTube, Spotify, or Apple Podcasts. Chapters:
(00:00) - Introduction
(13:20) - The origins of GLP-1 drugs
(46:07) - GLP-1s for everything?
(01:03:33) - Promiscuous drugs
(01:25:04) - Why isn't drug repurposing more common?
(01:56:39) - How to fix the incentives
Click here to view the episode transcript.
Saloni’s substack newsletter: https://www.scientificdiscovery.dev/ Jacob’s blog: https://blog.jacobtrefethen.com/ Acknowledgements: Aria Babu, editor at Works in Progress Graham Bessellieu, video editor Abhishaike Mahajan, cover art Atalanta Arden-Miller, art direction David Hackett, composer Correction: Saloni misdescribed the mechanism of immortal time bias - it comes from the pre-prescription time being counted in the treatment group, not the control group. Blogs Julia Rohrer (2018). The uncanny mountain: p-values between .01 and .10 are still a problem https://www.the100.ci/2018/02/15/the-uncanny-mountain-p-values-between-01-and-10-are-still-a-problem/ Abhishaike Mahajan (2025). Mapping the off-target effects of every FDA-approved drug in existence (EvE Bio) https://www.owlposting.com/p/mapping-the-off-target-effects-of Videos George Davey Smith (2026). Does the shingles vaccine prevent dementia? https://www.youtube.com/watch?v=qlTnnQytOJ0 Articles & reports Radwan Darwish et al. (2025). History of glucagon-like peptide-1 receptor agonists. https://doi.org/10.1016/j.phrs.2025.108045 Brian L. Furman (2012). The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent. https://doi.org/10.1016/j.toxicon.2010.12.016 Eric Budish, Maya M. Durvasula, Benjamin N. Roin, Heidi L. Williams (2026). Missing markets for innovation: evidence from new uses for existing drugs. NBER Working paper. https://www.nber.org/system/files/working_papers/w34222/w34222.pdf Babak Sahragardjoonegani, Reed F Beall, Aaron S Kesselheim, Aidan Hollis (2021). Repurposing existing drugs for new uses: a cohort study of the frequency of FDA-granted new indication exclusivities since 1997. https://pmc.ncbi.nlm.nih.gov/articles/PMC7780607/ BMJ (2020). Covid-19: The inside story of the RECOVERY trial https://www.bmj.com/content/370/bmj.m2670 Stephan Guyenet (2021). The future of weight loss https://worksinprogress.co/issue/the-future-of-weight-loss/ Kevin Hickey, Erin Ward (2024). The Role of Patents and Regulatory Exclusivities in Drug Pricing https://www.congress.gov/crs-product/R46679 Alex Kesin (2025). The three-thousand-year journey of colchicine https://worksinprogress.co/issue/the-three-thousand-year-journey-of-colchicine/ Natália Coelho Mendonça (2024). The promise of SGLT2 inhibitors https://worksinprogress.co/issue/the-future-of-kidney-treatment/ Samy Suissa, Laurent Azoulay (2012). Metformin and the risk of cancer: time-related biases in observational studies https://doi.org/10.2337/dc12-0788 Nicholas Reville (2026). Proposing an NIH High-Leverage Trials (HILT) Program. Center for Addiction Science, Policy, and Research (CASPR) https://caspr.org/policy/papers/HILT/ Web Smiths
More from Hard Drugs
What if treating diseases was as simple as telling your cells to stop making a harmful protein? That’s the premise of siRNA, a technology that silences genes without changing DNA. Just a single dose of siRNA can last for months. Better, it can be reprogrammed to silence a different gene or mutation by simply switching its sequence. In this episode, Jacob and Saloni explore why it took so long for siRNA to be turned into drugs, why most siRNA drugs so far have targeted liver diseases, and whether they could eventually be used to treat many diseases, from infections to heart disease to rare diseases to cancers. Hard Drugs is a podcast from Works in Progress about medical innovation presented by Saloni Dattani and Jacob Trefethen.
Malaria is caused not by a virus or bacterium, but by a complex, shape-shifting parasite that has evolved alongside us for millennia. This has made vaccine development a brutal challenge. In this episode, Jacob and Saloni are joined by Katharine Collins, who co-invented the second malaria vaccine, called R21, during her PhD. They discuss the gruelling process of reverse-engineering a vaccine and eureka moments along the way. They ask whether the biggest barriers to new vaccines are scientific or financial, and what it will take to finally eradicate one of natureʼs most vicious killers. Hard Drugs is a podcast from Works in Progress about medical innovation presented by Saloni Dattani and Jacob Trefethen. Timestamps: 00:00 Introduction 05:08 Our favourite parasites 10:12 How to invent a vaccine during your PhD 34:18 Why is it called the R21 vaccine? 37:32 Moving from the bench to billions of doses 41:43 The vicious life cycle of malaria parasites 46:15 Malaria research IN MICE 53:03 The murderer in malaria research 55:51 Would you volunteer to get infected by malaria? 1:08:21 Why did the first malaria vaccine take so long? 1:18:26 Could we have had the vaccine sooner? 1:40:48 Vaccine versus vaccine: which one’s better? 1:46:53 If we did this again today, could we make better vaccines? 2:04:55 Conclusion and our reasons for pessimism and optimism You can watch or listen on YouTube, Spotify, or Apple Podcasts. Saloni’s substack newsletter: https://www.scientificdiscovery.dev/
Heart disease is the leading cause of death worldwide, but it’s also one of medicine’s biggest success stories. Since the 1950s, the risk of dying from cardiovascular disease has fallen dramatically, thanks to public health efforts, emergency care, medical innovation, and surgeries. In this episode, Jacob and Saloni explore the cholesterol revolution: from statins discovered in fungi to new drugs that cut LDL cholesterol by 60% and last for months, driven by breakthroughs in genetics, monoclonal antibodies, RNA therapies, and modern medicinal chemistry. They talk about how cholesterol travels through the bloodstream, how it causes atherosclerosis and heart disease, and why it took nearly a century for scientists to form the consensus that lowering cholesterol saves lives. Hard Drugs is a podcast from Works in Progress and Coefficient Giving about medical innovation presented by Saloni Dattani and Jacob Trefethen. You can watch or listen on YouTube, Spotify, or Apple Podcasts. Chapters: 0:00:00 Introduction 13:35 The decline in heart disease mortality 31:02 Surprising facts about cholesterol 55:40 The lipid hypothesis: 7 lines of evidence for the harms of LDL cholesterol 1:22:15 How cholesterol works 1:30:40 The discovery of statins 1:48:44 Should everyone be on statins? 1:57:10 PCSK9 drugs and beyond 2:22:56 Summary Saloni’s substack newsletter: https://www.scientificdiscovery.dev/
Hepatitis B is a tiny virus that causes hundreds of thousands of deaths from liver disease and cancer each year. The vaccine against it became the first of many milestones: it was the first viral protein subunit vaccine, the first recombinant vaccine, and the first vaccine to prevent a type of cancer. In this episode, Jacob and Saloni follow the trail of strange jaundice outbreaks that scientists traced to a stealthy liver virus, how scientists turned one viral surface protein into a lifesaving shot for newborns, and how it was all built upon breakthroughs in immunology. Hard Drugs is a new podcast from Works in Progress and Coefficient Giving about medical innovation presented by Saloni Dattani and Jacob Trefethen.
Before vaccines became routine, they were risky experiments. In this episode, Jacob and Saloni travel back to the world of smallpox, cowpox, and cow-based “vaccine farms” to see how scientists stumbled toward the first vaccines against infectious diseases: smallpox, rabies, TB, polio, and more. Through the stories of milkmaids and aristocrats, secret lab notebooks, microscopes and cell culture, they explore how trial and error turned gruesome folk practices into the science of immunization, and how it all began with a single pustule. Hard Drugs is a new podcast from Works in Progress and Coefficient Giving about medical innovation presented by Saloni Dattani and Jacob Trefethen. You can watch or listen on YouTube, Spotify, or Apple Podcasts. Saloni’s substack newsletter: https://www.scientificdiscovery.dev/