Speaker
Dhruv Khullar
Appearances over time
1 episodes
Episodes
1
Podcasts
Quotes & moments
GLP-1 (glucagon-like peptide 1) was first discovered in the 1980s and initially studied for diabetes management.
A scientist studying Gila monsters discovered the lizard's venom contained a GLP-1-like peptide that could persist for hours, catalyzing the GLP-1 drug revolution.
Since the turn of the century, alcohol-related deaths in the United States have more than doubled.
It has been 20 years since the FDA last approved a medication specifically for alcohol use disorder.
Trial participant Mary lost 55 pounds in just 5 months on Ozempic, ultimately having to stop due to excessive weight loss, but she maintained her sobriety afterward.
Estimates suggest 1 in every 8 Americans has been on a GLP-1 medication at some point, amounting to tens of millions of people.
In some studies, half or more of people stop taking GLP-1 medications within a year of starting, limiting their long-term effectiveness.
The sticker price for GLP-1 medications can reach $1,000–$1,300 per month, making them inaccessible for many patients.
The first GLP-1 medication (exenatide) was approved around 2005–2006, meaning these drugs have a roughly 20-year safety track record, providing some reassurance about long-term effects.
Dhruv Khullar concluded that GLP-1s are not a magic bullet and work best as one part of a comprehensive set of lifestyle and behavioral changes.
Approximately 90% of drugs that make it to Phase 1 clinical trials ultimately fail before becoming approved medications, underscoring the need for caution around promising early data.
A new Eli Lilly drug called retatutride hits three GLP-1-related receptors — compared to one or two for current drugs — and has completed Phase 3 trials.
Studies show GLP-1 medications can slow or even reverse fatty liver disease and chronic kidney disease, effects that appear independent of weight loss.
GLP-1 was discovered in the 1980s, but it broke down in minutes — useless as a drug. The breakthrough came from an unexpected place: Gila monster venom, which contained a similar peptide that could persist for hours. That discovery launched one of the most consequential drug classes in modern medicine.
GLP-1s don't just reduce appetite — they appear to dampen dopamine spikes across every major addiction: alcohol, cocaine, nicotine, gambling, even social media. A neuroscientist told Khullar this suggests addiction has a single universal pathology, and GLP-1s may be part of how we fix it.
GLP-1s blunt the dopamine spikes triggered by cocaine, alcohol, and other addictive substances — but they don't drain dopamine entirely. Mice given GLP-1s and cocaine had smaller dopamine surges but maintained baseline neurotransmitter levels. The drugs moderate without eliminating the will to live.
For some patients, GLP-1s don't just moderate desire — they appear to extinguish it. Reports of anhedonia (inability to feel pleasure) and blunted mood raise serious questions about psychological side effects that remain poorly studied. A drug that makes you not care about anything is not the same as one that helps you care less about the wrong things.
Beyond weight and diabetes, GLP-1s appear to slow or reverse fatty liver disease, chronic kidney disease, and osteoarthritis — and may reduce cardiovascular and stroke risk. Some effects appear independent of weight loss, pointing to a possible anti-inflammatory mechanism. Even a physician who approached these drugs with skepticism has been repeatedly surprised by the evidence.
The GLP-1 landscape is about to get much more complex. Eli Lilly's retatutride hits three receptors versus the current drugs' one or two and has completed Phase 3 trials. Oral versions are coming. Within five to ten years, there will be many more options targeting specific side effects, muscle preservation, and different administration routes.
When a drug is powerful enough, it becomes tempting to stop addressing the social root causes — poverty, loneliness, trauma, the food environment — that produce the problem in the first place. Khullar worries that widespread GLP-1 use could reduce pressure to fix broken food systems and built environments. But he also acknowledges we've been failing at that work for decades, and people need help today.
Years before Ozempic existed, Khullar cared for a taxi driver who needed heart surgery but was too heavy to safely operate on. The surgeon said: lose weight, come back. Everyone knew that was impossible. Khullar still wonders whether GLP-1s could have given that man his shot. It's the clearest argument for why access to these drugs matters.
More than half of patients stop GLP-1 medications within a year, whether from side effects, cost, or access. The sticker price can hit $1,300 a month. The drugs also cause muscle loss alongside fat loss, raising frailty concerns — which is why high-protein diets and strength training are essential companions. These are not simple, affordable, or side-effect-free drugs.
Mary had tried rehab, AA, and Antabuse — and failed every time. Then she enrolled in a clinical trial for Ozempic. Within weeks, the craving was gone. She stopped drinking, lost 55 pounds, ended a bad relationship, and started exercising. GLP-1s didn't just treat her addiction; they gave her room to rebuild her life.
As AI reshapes medicine, doctors can no longer simply state evidence and expect compliance. The information landscape is too fragmented and too noisy. Storytelling — connecting data to real human lives — will become a core clinical skill. Physicians who can synthesize, narrate, and connect will thrive; those who can't will be replaced by an algorithm.
Aristotle preached moderation, but he lived in a world of scarcity. He didn't have Doritos, Krispy Kreme, McDonald's, TikTok, or fentanyl. Today's world is purpose-built to exploit our most basic neurological vulnerabilities. GLP-1s may be evidence that moderation isn't a moral failing — it's a biological challenge that requires biological tools.
Dhruv Khullar underwent the same MRI protocol as clinical trial participants, viewing images of food and alcohol while his brain was scanned. His brain barely reacted to alcohol images. People with alcohol use disorder's brains lit up. That visceral contrast drove home something years of medical training hadn't: addiction is largely predetermined by neurobiology, not character.
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- Health & Fitness 75%
- Society & Culture 17%
- Science 8%
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