Today, Explained – "Skinny and Sad on GLP-1s"

Vox | February 13, 2026 | Host: Jonathan Hill with Sydney Lupkin & Dr. Sarah Lavelle

Episode Overview

This episode dives into the booming world of GLP-1 medications (like Ozempic and Wegovy), their rapid rise thanks to celebrity endorsements and aggressive marketing, the controversial role of compounding pharmacies, and an unexpected psychological side effect: a loss of motivation and pleasure, or "flatness," some users report. Jonathan Hill hosts a discussion with NPR pharmaceuticals correspondent Sydney Lupkin and clinical psychologist Dr. Sarah Lavelle, exploring how these drugs are sold, who gets them, their regulation, and what it actually feels like to be on them.

Key Discussion Points & Insights

1. GLP-1 Drugs Go Mainstream

• Super Bowl Ad Blitz: Many weight loss drug commercials (including from celebrities like Serena Williams and Charles Barkley) aired during the Super Bowl, most advertising not official generics, but "compounded" versions made by pharmacies, not big pharma.
• [00:33] "Most of those ads, including Serena's, were for companies that offer knockoff versions of the popular drugs. So how is that legal?"
  —Jonathan Hill

The Economic Driver

• GLP-1s remain wildly popular; demand keeps growing.
• Many seeking these drugs feel desperate after lifelong weight struggles; stigma persists, but relief is found through these treatments.
• [01:52] "As someone who's talked to hundreds of patients who have taken both brand name and compounded GLP1s... they want to be taking them... this is a tool and it's really helped me."
  —Sydney Lupkin

2. Compounded GLP-1s: Is This Legal or Safe?

• What is Compounding?
  • Compounding pharmacies customize medications, initially for rare, individual patient needs (e.g., allergies to ingredients in commercial drugs).
  • FDA allows compounding "copies" ONLY if the official drug is in shortage.
  • Ongoing demand and past shortages led telehealth companies (Ro, Hers, Hims) to mass-market compounded GLP-1s, often at lower prices than official versions ($1,400+/month for WeGovy).
• Legal Gray Zone:
  • As shortages eased, official supply returned, but companies kept selling compounded versions, claiming legality by customizing doses. Debate rages over whether this is lawful.
  • [05:21] "Companies...think they're working within the parameters of the law. And there's some definite debate about whether that's true."
    —Sydney Lupkin

Pills Enter the Market

• Newly-approved oral GLP-1s hit pharmacies just a month ago, but telehealths quickly offered compounded versions.
• Legal pushback was swift: FDA warns it's illegal to mass-produce such compounds now that supply is back; companies like Hims pulled their pill offerings after HHS referred the issue to the Justice Department.
  • [08:00] "FDA will take swift action against companies mass marketing illegal copycat drugs ... the FDA cannot verify the quality, safety, or effectiveness of non-approved drugs."
    —Weight Loss by Hers Rep quoting FDA commissioner

Are Compounded GLP-1s Safe & Effective?

• Regulation is patchy:
  • Small compounders only get state board oversight, not FDA scrutiny.
  • No standardized US Pharmacopoeia (USP) "recipe," as would exist for approved generics.
  • Risks cited: incorrect dosing (too weak = ineffective, too strong = dangerous), unknown contaminants, long-term effects unknown.
  • [09:42] "If it's too strong and you don't know it, that can be really risky."
    —Sydney Lupkin

3. The Psychology of Weight Loss and "Flatness"

Reports of Emotional Numbness

Dr. Sarah Lavelle observes a concerning trend:

• Some patients on GLP-1s experience a "flat affect"—not classic depression, but a blunting of joy, motivation, and anticipation.
• [13:26] "I started noticing...they all kind of have this kind of flat affect ... not even excited to go out with my friends. What's so different about these patients? These three in particular had been on GLP1s."
  —Dr. Sarah Lavelle

What’s Really Happening?

• The drugs seem to dull the brain’s reward signaling — not just appetite, but also pleasure and motivation across activities.
• GLP-1s show potential for treating not just overeating, but also addictions (e.g., gambling, shopping, alcohol), supporting the "reward blunting" hypothesis.
  • [15:18] "You're also not getting, oh, I'm gonna see my friend later, or ooh, I can't wait to go to this concert. You're kind of dampening this anticipatory response."
    —Dr. Sarah Lavelle

Not Depression, Not Sadness

• It's not "sad" so much as "blah"—a flat, beige, indifferent state that doesn’t meet definitions of clinical depression.
• [17:05] "By altering their desire for food, some people say they've lost their desire for everything else. And what's left is a long lasting state of meh, blech, numb, flat, take it or leave it."
  —Jonathan Hill

Clinical Nuance: Not One-Size-Fits-All

• For some, especially those desperate for weight loss after binge eating disorder, GLP-1s can be transformative and psychologically hopeful.
• For others (e.g., those prone to or recovering from anorexia), the same drugs can be dangerous, eliminating food thoughts entirely in a way that supports unhealthy behaviors.
• [18:25] "If you are 100 pounds overweight and you're extremely upset about it and you've given up all hope, I think GLP1s can be not just this physical lifesaver, but this light at the end of the tunnel for you. Right? But then ... people with anorexia... it's their dream drug. ... That's a huge problem."
  —Dr. Sarah Lavelle

Risks of Coming Off:

• Discontinuing the drugs can result in overwhelming cravings, greater than before, unless carefully prepared for—possibly reinforcing self-blame.

Societal Implications

• Prevalence: 1 in 8 adults now reports using GLP-1 drugs; more may follow if affordability increases.
• Will "Flatness" Become Widespread?
  Dr. Lavelle is cautious, not alarmist, likening the adjustment to concerns over widespread Prozac use in the past. She notes:
  • Society may find balance over time.
  • Not everyone should take these drugs; careful selection and monitoring are key.
  • The dampening of reward may explain why users struggle with motivation to exercise or pursue healthy food, potentially complicating the intended outcomes.

Notable Quotes & Memorable Moments

• [01:52] Sydney Lupkin:
  "I've talked to people who have said, you know, I have struggled to lose weight my entire life and this changed my life."

• [05:21] Sydney Lupkin:
  "The list price for WeGovy is like $1,400 a month. So all of a sudden people could get it for cheaper."

• [08:00] FDA Warning (voiceover):
  "The FDA cannot verify the quality, safety, or effectiveness of non-approved drugs."

• [15:18] Dr. Sarah Lavelle:
  "You're dampening this anticipatory response ... It’s not just changing your appetite and metabolism. ... What kind of positives might that be dulling?"

• [17:05] Jonathan Hill:
  "By altering their desire for food, some people say they've lost their desire for everything else. And what's left is a long lasting state of meh, blech, numb, flat, take it or leave it."

• [18:25] Dr. Sarah Lavelle:
  "I think GLP1s can be not just this physical lifesaver, but this like light at the end of a tunnel for you ... but ... people with anorexia ... it's their dream drug ... to me that's a huge problem."

• [21:49] Dr. Sarah Lavelle:
  "I'm not willing to be fearful of that ... Not everybody should be on it, but there's some people who are gonna really benefit ... There are some, just like Prozac."

Timestamps for Important Segments

• 00:33: Super Bowl GLP-1 ads and introduction to compounded drugs
• 01:52: Patient stories and the life-changing impact of GLP-1s
• 05:05-06:17: Compounding vs. generics, legal loopholes, and economic pressures
• 08:00: FDA and HHS crack down on compounded GLP-1 pills
• 09:42: Risks and uncertainty around compounded drugs' safety and effectiveness
• 13:26: Dr. Lavelle introduces the "flat affect" symptom in GLP-1 patients
• 15:18: Theory: Dopamine and reward dampening by GLP-1s
• 18:25: Nuanced effects — GLP-1s as blessing for some, danger for others
• 20:16: Preparation needed for patients discontinuing GLP-1 therapy
• 21:49: Societal impact, normalization fears, and finding balance

Conclusion

The episode presents a balanced yet sobering picture: while GLP-1s offer hope and assistance to many battling obesity and binge eating, the route they're delivered (compounded, sometimes questionably legal) carries risks. More importantly, an unforeseen psychological toll—emotional blunting or loss of motivation—may soon shape both individual and societal experiences as these drugs proliferate. The need for careful regulation, individual assessment, and attention to mental health outcomes is clear: "Skinny" may come at the price of "sad"—or, more aptly, of feeling nothing at all.