5HT: 5 Healthyish Things, a special microdosing GLP-1s edition

Time for a short history lesson 🤓. In the 1990s, Dr. John Eng, a government researcher, discovered Gila monsters have a special hormone in their venom: Exendin-4. The hormone acts similarly to a hunger-regulating hormone in humans, which helps control blood sugar levels called glucagon-like peptide-1. Yup, what we (and even your mom) now affectionately refer to as GLP-1.

A key difference is the Gila monster exendin-4 breaks down much slower than the human version of GLP-1—lasting hours instead of just a few minutes. And that longer half-life makes it a way better starting point for drug development. Seeing the potential to commercialize the discovery, Eng patented the molecule in 1995 and later licensed it to a biotech startup called Amylin, which used his Gila monster research to create a synthetic hormone called exenatide. 

Fast forward a decade: The Food and Drug Administration (FDA) approved exenatide, the first GLP-1 mimicking drug, to treat type 2 diabetes in 2005 and opened the door to a new class of medications. Over time, they’ve evolved (and blown up) to target obesity, too. 

Aand hit the fast forward button again ⏩ Today, one in eight U.S. adults have tried a GLP-1, according to 2024 research, and studies consistently show GLP-1s are extremely effective at lowering blood glucose and achieving weight loss.

Thank you, Gila monster! 🦎

Now, let’s move on to a science lesson 🧑‍🔬. To wrap your head around how GLP-1s work, knowing how GLP-1 (a naturally occurring hormone) functions in the human body is helpful. GLP-1 is a hormone your small intestine makes, and it does some pretty cool stuff like:

• 1️⃣ Boosts insulin. GLP-1s nudge your pancreas to release more insulin, helping your cells turn food into energy and reducing blood sugar.

• 2️⃣ Blocks glucagon. GLP-1s act as a bouncer to glucagon, the hormone that tells your liver to release sugar.

• 3️⃣ Slows digestion. GLP-1s slow gastric emptying, meaning less glucose (sugar) is released into your bloodstream from the food you eat.

• 4️⃣ Signals fullness. GLP-1s talk to the part of your brain that controls appetite, helping you feel full sooner (and stay that way longer).

GLP-1 medications work by mimicking the hormone. They latch onto GLP-1 receptors to trigger the same effects. (Similar to melatonin and insulin.) Visualize it like this: The medication hops into the sidecar and rides shotgun with your body’s own GLP-1.

As a side note, it’s worth saying we weren’t built for a world flooded with ultra-processed food, empty calories, and constant exposure to metabolic stressors. GLP-1s, IMO, help us counter that nonsense in a way that’s pretty miraculous.✨

According to Pew Research, three-quarters of Americans have reportedly heard of GLP-1 drugs, but with names like Mounjaro and Rybelsus, it’s hard to know what’s what. (And don’t get me started on orforglipron. 😵‍💫) 

Currently, two pharma giants dominate the GLP-1 space: Novo Nordisk and Eli Lilly. Others—like Amgen, Pfizer, Altimmune, and Structure Therapeutics—are working on next-gen versions and may not be far behind. 

Novo Nordisk is the company behind Ozempic, the OG GLP-1 made famous by celebrities (yes, even Oprah) and powered by the active ingredient semaglutide. Eli Lilly, on the other hand, uses tirzepatide in its blockbuster drugs. The two are often compared in clinical trials—but while they duke it out, here’s how their biggest drugs stack up 👇: 

There’s a reason why GLP-1 has been dubbed “the miracle drug.” In fact, there are a few. Let’s start with weight loss.

More than 2 in 5 U.S. adults (42.4%) live with obesity today (up from 13% sixty years ago). Obesity is a condition linked to many “comorbidities” (a rude way of saying “other conditions”) like diabetes, cardiovascular diseases, and depression, and research shows even losing just 5-10% of your body weight can reduce chronic disease risk. So when we give people a real way to manage their weight, we’re also helping them prevent serious health issues and invest in their health and lifespan. 

And in a country where healthcare costs have skyrocketed, the financial upside of reducing obesity is massive—not just for individuals but for employers, too. A quarter of U.S. employers report obesity has the largest impact on overall health costs. Thankfully, new research suggests GLP-1s could cut long-term healthcare expenditures.

So, just how miraculous are we talking? In a 72-week trial of adults with obesity or overweight (but without diabetes), participants on 15mg of Zepbound lost 20.9% of their body weight on average. Even those on the lowest dose (5mg) saw a 15% drop. Study after study of Zepbound, Wegovy, and other GLP-1s show similarly dramatic drops.

Plus, GLP-1s are really great at multitasking. Because while GLP-1s dominate headlines for weight loss, there’s also a growing range of ancillary benefits found in studies. Let’s break them down. 👇

• 🫀 Heart health: A meta-analysis of people with type 2 diabetes found GLP-1s reduced the risk of major cardiovascular events—like heart attack, stroke, and cardiovascular death—by 14%.

• 🧠 Brain health: A real-world study of 160,000 adults with type 2 diabetes found those on GLP-1s had a 45% lower risk of developing Alzheimer’s and other dementias compared to those on other diabetes medications. (Given my personal focus on this, I was shook).

• 🦠 Gut health: A 2025 systematic review found GLP-1s can shift gut bacteria linked to better metabolic health in animal and human models (though effects varied by drug, population, and study duration.)

• 🛡️ Inflammation control: Research shows GLP-1s can reduce inflammation and cellular stress across multiple organs—including the heart, kidneys, and lungs—which matters because chronic inflammation drives many major diseases. (Planning another special edition planned on this topic.)

• ⬇️ Cancer risk reduction: A study published in The Lancet found GLP-1s were linked to a 48% lower risk of obesity-related cancers compared to other diabetes medications.

• 🫂 Mental health: A 2025 systematic review found GLP-1s were associated with reduced depression and psychological distress, improved emotional well-being, and greater day-to-day functioning in people with obesity and type 2 diabetes.

• 🫁 Lung health: A 2024 review suggests GLP-1s may support respiratory health by reducing airway inflammation, modulating immune response, and promoting weight loss in people with asthma and other lung diseases.

🫱 Addiction support: A 2024 study found people with alcohol use disorder on semaglutide had fewer alcohol-related medical visits, suggesting GLP-1s may help reduce alcohol use and cravings. (Lots more research happening here).

That said, there are side effects we know about—and long-term risks we still don’t fully understand.

The most common issues are GI-related: nausea 🤢, vomiting 🤮, diarrhea 💩, and constipation 🚽. Among these, nausea is by far the most frequent. According to Dr. Saundra Nguyen, assistant professor of internal medicine at Baylor College of Medicine, these effects can improve as your body adjusts—or worsen with higher doses. FWIW, I haven’t experienced any, but I know plenty of people who have.

As more studies emerge, so do more serious (though rarer) side effects. A 2025 study in Nature found GLP-1 use increased the risk of low blood pressure, fainting, joint pain, kidney stones, kidney inflammation, and drug-induced pancreatitis. There’s also nuance around cancer risk. JAMA research shows a potential increase in kidney cancer risk, but the same study also found that GLP-1s may reduce the risk of 10 other obesity-related cancers.

Muscle density 💪 and bone health 🦴 are other areas of concern. A study in The Lancet found that 25–39% of weight lost while taking GLP-1s came from muscle, not fat—higher than the 10–30% range seen with non-drug calorie restriction. However, researchers suggest this loss is likely due to the amount of weight lost rather than a direct side effect of the drugs themselves. (This is one that I’ve been very concerned about, though I’m relatively sure the numbers ultimately are pretty consistent with any dramatic loss of weight.)

In another study out of the University of Colorado, fracture risk increased in people with obesity (but not diabetes) who were prescribed a GLP-1 compared to those who weren’t. Since rapid weight loss is already known to reduce bone density and muscle mass, it’s likely GLP-1s don’t cause the problem outright but potentially accelerate it.

An example of early signals being misinterpreted as causation: In 2023, reports surfaced saying GLP-1s were causing suicidal thoughts. But, after a full review, the European Medicines Agency found no causal link between GLP-1 use and suicidal or self-injurious behavior.

Taking a step back, it doesn’t seem we’ve discovered some terrible side effect/legitimate reason not to use these things. So far, it seems almost all the bad is tied to the same good—a lot of weight loss. People have also been taking GLP-1s for 20 years, so not like a hot second.

Nonetheless, this is one heck of a mass clinical study we’re doing right now on the general population—and it’s totally plausible we could find something that stops everyone from using it (or think even harder about the trade offs) in the future–so there is absolutely some risk. Bottom line: We need more long-term research to really understand causation and long-term risk. Right now, it’s a lot of IDKID. 🤷‍♂️

Okay, I promised you a GLP-1 microdosing special edition—so let’s get into it. 👉 Microdosing has been buzzy for a while now, especially in the world of mushrooms and other psychedelics. There’s also an underground movement of folks who use microdose prescription drugs like stimulants (Adderral/Ritalin), antidepressants, "benzos" (like Xanax), and others. Now, GLP-1s are the latest drug to join the trend.

“Microdosing Ozempic” has taken off online—covered everywhere from The New York Times to Goop—and has become especially popular in the SoCal community (because, duhhh), the menopause community, and apparently among Gen Z. What a spread. The basic idea: Take a smaller “sub-therapeutic” dose (see chart above) of a GLP-1 to get subtler benefits with fewer side effects (or potentially less long-term risk, too).

People are microdosing for various reasons—from reducing side effects and managing cost (these drugs are expensive and rarely covered by insurance—though some employers are pitching in) to improving access or simply wanting to lose a smaller amount of weight. And while there’s still no clinical research confirming its safety or efficacy, several doctors told The Hollywood Reporter their patients have experienced benefits like improved clarity, reduced compulsive behavior, and modest weight loss.

Reddit has also blown up about GLP-1s. There are tons of threads 💬 with people giving and asking for advice on microdosing—from dosage to mitigating side effects (which we’ll get into below)—essentially becoming a community for microdosers to trade tips and experiences. 

Search interest in “microdosing GLP-1” has surged ↗️ especially in the past few months.

One of the first times I personally heard about microdosing weight-loss drugs was when our favorite biohacker, Bryan Johnson, posted about his plan to microdose tirzepatide on X—driven not to lose weight but for longevity benefits. 

About a month later, he halted his experiment, citing an increased resting heart rate, lower HRV, and worse sleep. For him, the hit to sleep quality outweighed any theoretical benefit of microdosing GLP-1s. Of course, this is just one uber-optimized personal story (and a very edge one at that).   

While some experts remain skeptical, others say microdosing a GLP-1 drug is not inherently more dangerous than taking a standard dose—if you have a legitimate prescription and are working with a doctor. (There could be, however, more risk involved with compounded GLP-1s since they lack FDA approval.) This also seems like a good time to remind everyone I’m not a doctor but a friend with health benefits 😆.

Speaking of anecdotal evidence, let’s get into mine. I’ve been on a weight loss journey this year. And, if you’ve been a 5HT reader for a while, you’ve been on that journey with me. (Whether you like it or not 😆.)

Even though I live pretty healthyish, I’ve gained about 20lbs+ since having kids…and also because of stressful work and the ridiculous amount of breakfast tacos in Austin. 😋 With my bad back (another journey 5HT readers have been forced to be on), some elevated heart biomarkers, and just getting older generally, it became clear I needed to take action.

I lost about 10 lbs on my own early in the year (through, duh, eating better and working out more). Then, I got a prescription for GLP-1s from my PCP and started microdosing the peptide in February. I’ve been administering 1.25 mg of tirzepatide weekly, a quarter of the standard therapeutic dose. Since then, I’ve lost another 15 lbs—and I’m basically at my goal weight. 🙌

FWIW (because I know we’ve got some sticklers here, lol), the Journal of Psychopharmacology defines a “true” microdose as just 1% of an active dose. Buuut since most people talking about GLP-1 microdosing just mean a smaller-than-prescribed dose, that’s what I’m referring to here.

Four months in, the experience has been suuuper interesting. The wildest part is I don’t think about food anymore. Like, the food noise is just gone. Logically, I know I need to eat, but eating is not something on my mind 24/7. I still enjoy food when I eat it. I just eat a lot less. As someone who grew up the biggest kid in the class, I still have constant food noise. But not on tirzepatide. It’s all pretty… zen?

The only thing that’s not zen is giving myself a shot every week. 💉 I’m not part of the 30% of people afraid of needles, but I wouldn't say I’m a big fan of injecting myself, either. 😅 That said, the results have been worth the weekly poke.

I’ve been lucky not to experience side effects so far—but I’ve also been pretty proactive about minimizing the risk. Here’s what I’ve been doing:

• 🏋️‍♂️ Exercise: I strength train hard three days a week in my at-home gym to preserve muscle mass and go rock climbing a fourth day.​ (Doctors say exercise—particularly strength training or bodyweight exercises—can help preserve bone density for those taking GLP-1s.)

• 🦠 Gut support: I’ve added fermented foods to my meals (I basically have kimchi or sauerkraut with my breakfast every day) and probiotics to my supplement stack (check my latest probiotic regimen) to support digestion and counter potential GI side effects.

• 🍗 Protein intake: I’ve kept my protein intake sky high—aiming for one gram per pound of body weight (shout out Pioneer Pastures—my go-to protein shake) to preserve lean muscle and boost satiety. 

• 🧪 Health monitoring: I’ve been getting regular bloodwork to make sure my body’s responding well.​ I haven’t done a DEXA scan yet (I should), but I did do a Prenuvo for a full-body baseline.

Of course, everyone’s body reacts differently. So, if you’re on GLP-1's full dose or low dose, here’s what Harvard Health recommends to curb tummy problems:

• Vomiting: Stay hydrated and eat smaller, more frequent meals.

• Nausea: Avoid strong smells; try crackers, mint, or ginger-based foods/drinks ~30 minutes post-dose

• Diarrhea: Double down on water and skip dairy and high-fiber foods until it eases.

• Constipation: Boost fiber and fluids.

Further recommendations backed in Diabetes Therapy include dosing at night to sleep through peak side effects, monitoring your electrolytes, and skipping high-fat or sugary meals. Of course, if you’re dealing with any side effects, the best thing to do is talk to your doctor 🩺.

So I was at a kiddo pool party recently… and felt really good 😎. I’m down 25 lbs, I’ve added muscle, and I feel really confident in my skin for the first time in a while. (I’ve always been confident, but this sure helps.)

While there, I found myself looking around at all the other people who looked great too (yes—men compare themselves too). And I couldn’t help but wonder: How many of them are on GLP-1s? How many are thinking about it?

I’m genuinely happy with how my experience has gone and did my homework before committing. That said, I would cautiously recommend it to others. IMO it’s probably not worth any long-term risk if you don’t actually need to lose much weight.

As far as whether I’m going to keep taking them, IDKID. My original plan was a 6-month experiment, and now that I’m basically at my goal weight, I’m leaning toward stopping. Honestly, more evidence for dementia & Alzheimer’s prevention could sway me in the future, but for now, I think my next challenge will be maintaining without ‘em, and that sounds like a pretty great challenge.

Anyway, yes, I’ve personally felt the benefits—improved appetite control ✅, a clearer head ✅, and real weight loss ✅—all at a low dose. But as I shared earlier, I’m also hyper-aware that we still don’t know a lot. What if we do find a crazy smoking gun? 🤷‍♂️ Plus, taking prescription drugs forever isn’t what I’d recommend.

It comes down to weighing risk vs. reward and making the best choice for your health. I’m happy with my progress—and for now, it feels like enough. So, I think I’ll hit pause, coast where I am, and stay curious about what the science says next.

Again, I’m not a medical expert. Buuuut, from the research I’ve seen, anecdotes I’ve read, and personal experience I’ve had, it does seem like many people could benefit from GLP-1s. I am ultimately more and more convinced this is, in fact, a miracle pill with the potential to transform everything—and I’m not even sure we’re talking about GLP-1s and their potential impact—on our healthcare system, costs, consumer goods, etc.—enough.

The conversation is clearly shifting from “Should we be taking these?” to “How should we be taking these?” Because, at this point, GLP-1s have moved from hype to habit. 

According to IQVIA, of the 15.5M obesity-related GLP-1 prescriptions filled in 2024, 83% were renewals. Access is also expanding—through employer-sponsored plans and DTC models (I still can’t get over whoever coined it “pharm to table” 😆), and it will only grow as demand continues to rise, prices drop, and pills hit the market (that’s going to be massive).

Looking ahead, I expect more studies to roll out (hopefully on microdosing!), more players to enter the space (already happening), more innovative products and form factors, and eventually, more personalized GLP-1 therapies tailored to individual genetics, metabolism, and goals (think: GLP-1s meet precision medicine). 

Imagine a world where almost everyone is taking GLP-1s—from your mom to Stacy’s mom, who will now really have it going on. (Sorry). In that world, I think microdosing won’t just be an edge-case experiment—it could be the default. Only time (and research) will tell. For now, happy microdosing—or not.

Okay, so if you're micro-interested in microdosing 😜, the first step is to talk to a real doctor—ideally one familiar with GLP-1s and your goals (i.e., weight loss, appetite control, metabolic health, etc).

You’ll need a prescription, and insurance typically won’t cover it unless you have a pre-existing condition. Now that compounded GLP-1s are mostly off the table, you can expect to pay $350/month (plus doctor visits) out of pocket. Your doc should ask you to get labs, so plan for that, too. Popular virtual clinics to consider are Ro, Hims & Hers, Found, Noom Med, LillyDirect (where I get mine), and now Novocare Pharmacy.

And don’t forget: Micro literally means less. Be okay with getting slower results. (That’s the point 😉.)