Hi, it's Helaine.
This weekend I published the longest, most researched piece I've written so far. It's about why GLP-1s get serious judgement, and the internal struggle with that judgement even for those on them.
I dug into the 2,500 year history of moralizing about women's bodies, the $80B diet industry that has a vested interest in keeping the willpower story intact, the jealousy layer nobody wants to name, and the reframe of the word "shortcut," which is doing a lot of damage. Better way to look at it: it's a leveling of the playing field. There's also a section on celebrities who have gone too far, and where the body positivity movement fits into all of this.
Fun throwback moment: the Jesse Spano on caffeine pills situation turns out to be a precursor of the whole thing. I'm so excited. I'm so excited. I'm so... scared. 😳
🎧 What I'm reading and listening to
If you only have time for one piece of GLP-1 content this week, make it this one:
Ezra Klein, a longtime journalist, interviewed Julia Belluz for two hours on his podcast last Friday. Belluz is a New York Times Opinion contributor and co-author with NIH researcher Kevin Hall of Food Intelligence. She has been reporting on this drug class for years.
The conversation holds two things at once. How meaningful these drugs are for so many people. And why we are at a moment in history where so many of us need them. The American food environment has failed us in too many ways to count. We have engineered a world of hypersugary, hyperprocessed, hyperavailable food and then handed people willpower as their only defense. That part is not biology. That part is design.
A few moments that stayed with me:
1. Klein tried tirzepatide and got anhedonic.
Klein lost roughly 50 to 60 pounds at 16 and has been open about managing his weight ever since. He knows food noise the way a lot of us do. "If we had a bowl of Oreos on this table, 30 to 50 percent of my mental energy the whole time we were talking would be to not eat the Oreos." (Honestly, same bro).
He tried the lowest dose of tirzepatide. It worked. He stopped wanting to eat. He also stopped wanting much of anything else.
"It was, in a way, revelatory. The problem is, it made me quite depressed and anhedonic."
Anhedonia, the flattening of the pleasure response Klein describes, has been showing up in patient reports and in the New York Times reader survey Belluz conducted earlier this year. It's not formally listed on most GLP-1 labels, but pharmacovigilance databases show psychiatric adverse events accounting for roughly 4.5% of all reported GLP-1 adverse events, with women representing 65% of those reports (Frontiers in Endocrinology FAERS analysis).
2. Hunger lives in the brain, not the stomach.
The old story was that hunger comes from your stomach and your brain decides whether to listen. The actual story is that your brain runs the whole symphony, and your stomach is one of many inputs. 🤯
Genome-wide research has identified more than 1,000 genetic variants associated with obesity, almost all of which act in the brain, not in fat tissue (Nature Genetics multi-cohort GWAS). Kevin Hall's randomized controlled trial at the NIH found that people eating an ultra-processed diet consumed roughly 500 more calories per day than people on an unprocessed diet, with identical calorie and macronutrient profiles available (Cell Metabolism, 2019). The food itself was rewiring the eating, not the willpower.
This was one of my favorite sections of the conversation and I’m excited for more research here.
3. The benefits keep getting weirder.
Belluz outlines three buckets where these drugs seem to be helping people: weight, inflammation, and direct organ effects. Cardiovascular protection. Kidney protection. Liver protection. Possible dementia prevention. Reduction in addictive behavior. Most of it is weight independent. Nobody fully understands why.
The question Klein puts to her halfway through: if these drugs do all of this, should everyone just be on them? Should it be in the drinking water? Her answer is no, not yet. There is too much we don't know. The most aggressive experimentation is happening outside the medical system, in research-chemical territory ordered from China, with no oversight.
4. The part of the conversation I can’t stop thinking about: kids.
Klein asks Belluz to imagine being a chubby 16 year old today. Would he have asked his parents for a GLP-1? Would his whole life have been different if he had?
I’ve been asking myself this about young Helaine ever since Friday.
What we know so far: about 1 in 5 US adolescents has obesity (CDC). The American Academy of Pediatrics endorsed GLP-1s for kids 12 and older in August 2023. Prescriptions for weight management drugs in kids jumped 65% after that, but only 0.4% of eligible children actually started using them (Truveta Research). Trials are underway in kids as young as 6. In adolescents, nearly 75% on semaglutide hit 5% or greater weight loss compared with 18% on placebo (AAMC review). The long-term effects on growth, puberty, and development are not yet known. Neither is the eating disorder risk.
The question Klein asked Belluz is the zinger: if this had been available when I was younger, what would I have done? What would I have missed? What would I have been spared? Belluz, who has young kids, was honest about being scared.
Would you go on this as a kid / adolescent or encourage your child to? I want to know - answer anonymously here.
TLDR; It is too early, we need more long-term research, there is no good answer yet.
📱 If you can't make time for a two hour podcast, here is who I think is worth following
Last week the Pew Research Center reported that 40% of US adults get health information from social media influencers and podcasts. Only 17% of those creators are doctors or nurses. 53% of uninsured Americans rely on these sources entirely (Pew Research, May 7). Yikes.
If we are getting health information from our feed anyway, might as well stack it with credentialed viral sensations. So I picked a few based on my criteria, three things:
Credentials line up with what they are speaking about
No obvious financial conflicts
Willing to disagree with each other in public, sometimes loudly.
None of these people are perfect. Everyone with an audience is also growing an audience, and that creates incentives. But the criteria above mean you can listen with your guard down a little.
Dr. Spencer Nadolsky. Obesity medicine physician. The most credible day-to-day voice on GLP-1 protocols I have found.
Dr. Mary Claire Haver. OB/GYN, menopause specialist. The clearest voice in the country right now on hormones, midlife, and how GLP-1s interact with both.
Dr. Stacy Sims. Exercise physiologist focused on women specifically. Most of what you have been told about exercising and eating as a woman is based on male data. She is fixing that.
Dr. Eric Topol. Cardiologist, founder of Scripps Research Translational Institute, author of Super Agers (2025). The closest thing we have to an evidence-only voice on what GLP-1s are actually doing across the body, beyond weight loss. Heavy on the science, light on the hype.
Dr. Vonda Wright. Orthopedic surgeon. The body as you age, with a women's lens.
Some popular names you will notice are not on this list. The omissions are intentional. The most common reason is a mega financial relationship with the products being discussed.
🚫 Myth I want to bust: it doesn't matter where you inject
Open any GLP-1 forum and you will find someone insisting that the abdomen is better than the thigh, or the thigh is better than the arm, or that injecting in the wrong spot is going to wreck your absorption. The actual research tells a much calmer story.
There is one small absorption difference worth knowing. A pharmacokinetic analysis found thigh injections deliver about 12% less bioavailability than the abdomen (Diabetes Therapy population PK analysis). The researchers themselves characterized this as not clinically relevant. All three FDA approved sites (abdomen, thigh, upper arm) achieve therapeutic blood levels and produce equivalent clinical outcomes. Pick the one that hurts least, fits your routine, or you can reach.
What about the need for "rotate or else" content to avoid lipohypertrophy, the scar-like fatty tissue that builds up at the injection site? A 2024 systematic meta-analysis published in Diabetes Technology & Therapeutics put it plainly: "Despite a comprehensive literature review, we found no scientific evidence regarding the potential link between lipohypertrophy and glycemic control in patients receiving GLP-1 analogs" (Mader et al., NIH PubMed Central).
Lipohypertrophy is overwhelmingly an insulin phenomenon. Insulin is itself a growth factor and actively stimulates fat cell growth at the injection site. The 42% to 64% prevalence numbers come from insulin patients injecting multiple times a day for years.
A year of weekly GLP-1 injections is roughly 52 shots. A year of basal insulin is closer to 1,400. The science is being copy-pasted between the two, and a lot of people are being scared into rotation protocols they don't need.
The reasonable rule: don't hit the exact same spot every single week. Move around within whatever site you use. The medication is not going to stop working because you have used your left abdomen four weeks in a row.
📺 What I'm watching: Maine just layered lifestyle requirements onto GLP-1 coverage
Maine's state employee plan, covering 26,000 workers, now requires enrollment in a Virta-run lifestyle program for continued GLP-1 coverage on the weight-loss indication (Press Herald, May 7).
Coverage is getting cut everywhere, and we have talked about why. The interesting part is what Maine is doing instead of cutting. The logic is that GLP-1s work best when combined with lifestyle change, so the plan will cover the drug if you are also doing the lifestyle work. It is the first state to layer real lifestyle requirements on top of coverage as a condition of access. I like this and worth watching where this goes.
One ask before you go. If this has been useful, the best thing you can do is forward it to one woman you think needs to read it. And if you have not subscribed to the Substack, that is where the deeper conversation is happening this week.
See you next week.
Helaine
Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.