Compound
Everything we've written on Semaglutide — 18 articles covering the mechanism, the evidence, comparisons, and practical considerations.
18 articles
Metabolic healthCagrilintide and the amylin story — why CagriSema is generating interestFor about a decade, obesity pharmacology was a field that kept almost delivering. The compounds that made it through the regulatory process were real drugs with real effects, but the effect sizes were modest by the standard of what the clinical need demanded — five percent body weight, eight percent, numbers that mattered medically but didn't shift the felt experience of treatment from incremental to transformative. Then the GLP-1 receptor agonists arrived at full dose in obesity indications, and the conversation changed. Fifteen to twenty percent body weight reduction in clinical trials was a number that made physicians and patients alike recalibrate their model of what was pharmacologically achievable. The question that immediately followed — among researchers, clinicians, and the industry watching closely — was not whether this was sufficient, but what would come next.8 min readMetabolic healthFood noise — the obsession with eating you can't think your way out ofIt starts before breakfast is over. You're still eating and already thinking about lunch — what you'll have, whether that's too much, whether you should have eaten what you just ate, what you'll do to compensate. By mid-morning there's a quiet negotiation running in the background: if you skip the afternoon snack, you can have a real dinner. If you have the good lunch, maybe just a small dinner. You're not even hungry. You're just... in it. The loop is running whether you want it to or not.8 min readMetabolic healthGLP-1s and alcohol — the off-label effect nobody planned forYou started semaglutide for your weight, and somewhere around week six you noticed something nobody warned you about. The glass of wine you poured at the end of the workday sat on the counter. Not because you decided not to drink it. You just forgot it was there. The craving that usually showed up around 6 PM — specific, familiar, a little impatient — didn't. And then the next night, same thing. And the night after that. You mentioned it to a friend who was also on a GLP-1 and she laughed and said she'd stopped buying wine entirely because she kept letting bottles go bad.7 min readMetabolic healthThe GLP-1 family tree — from Exenatide to RetatrutideIn 2005, a diabetes drug derived from gila monster venom got approved by the FDA and most people shrugged. Endocrinologists noticed. A handful of researchers noticed. The broader world did not. Seventeen years later, the cultural conversation around weight and metabolism would be transformed by a molecule descended from that same biological lineage — and suddenly everyone wanted to understand where it came from. The GLP-1 family tree is the answer to that question. It's a story of pharmaceutical iteration, each generation solving problems the last one left behind, each generation expanding what the biology could be asked to do.9 min readOrigins and discoveryThe history of GLP-1 research — from Habener and Drucker to OzempicIn 1987, a paper appeared in the Proceedings of the National Academy of Sciences describing the structure of proglucagon — the precursor protein that the body cleaves into multiple peptides depending on which tissue is doing the cleaving. Joel Habener's laboratory at Massachusetts General Hospital had worked out the sequence and identified, buried inside it, two peptides that looked like distant relatives of glucagon. They called them glucagon-like peptide-1 and glucagon-like peptide-2. The paper was read by people who study pancreatic hormones. It was not a cultural event. Nobody wrote about it in a newspaper. The molecule's future wasn't legible yet from what Habener's group knew at that point.9 min readWomen's hormonal healthGLP-1s in perimenopause — when nothing else is workingYou are eating the way you ate at thirty-five. You're training four days a week, sometimes five. You sleep reasonably well, you don't drink much, you track your food on and off and it's not dramatic. And the weight is still going in the wrong direction, or it isn't moving at all, or it's moving to your abdomen and waist in a way it never did before and no amount of core work touches it. You've been told it's stress. You've been told it's perimenopause and to just wait it out. You've been told your labs are normal. And you're standing in a body that feels like it's operating on entirely different rules than the one you've lived in for the last two decades.4 min readMetabolic healthWhy the scale stops moving on a GLP-1 — and what to do about the plateauThe first three months were real. The number moved every week — sometimes every few days. Clothes fit differently. People asked if you'd done something different. You had more energy in the afternoon. And then, somewhere around month four or five, the scale stopped. You're eating the same way. You haven't quit the medication. The number just sits there, stubborn and unmoved, and the quiet voice that says maybe this is it, maybe this is as far as it goes, gets a little louder every week.4 min readMetabolic healthWeight regain after stopping a GLP-1 — what's biological, what's behavioral, what to doYou lost thirty pounds over nine months. You ate less without fighting yourself about it, which was new. The background noise of food — the constant low-level negotiation between wanting something and deciding not to have it — went quiet in a way it never had before. And then, for whatever reason — cost, the medication becoming unavailable, your provider recommending a break, your own decision — you stopped. The quiet lasted maybe three weeks. And then the noise came back.3 min readMetabolic healthMicrodose GLP-1: who it's actually for, and what "microdose" really meansYou lost the weight. Not all of it, but enough — and then life happened, or the stress came back, or perimenopause shifted the whole calculus, and slowly the scale started moving in the wrong direction again. Not dramatically. Five pounds, then eight. The cravings that had gotten quiet started getting louder. You've heard about GLP-1 medications, but the idea of full-dose — the nausea, the muscle loss concerns, the appetite suppression so aggressive you stop eating enough protein — feels like more than the problem warrants. There should be something in between, and you're not sure whether that's a real clinical option or just wishful thinking.5 min readMetabolic healthMicrodose vs full-dose GLP-1 — picking the right intensity for the right goalYou've done the reading. You know GLP-1 receptor agonists exist. You know they work. But the conversation around them — the before-and-afters, the celebrity speculation, the prescribing provider ads — all seems to point at one thing: the full dose, the dramatic weight loss, the transformation narrative. And that's not quite what you're looking for. Or maybe it is, and you're not sure. You're trying to figure out whether the intensity of the intervention matches the intensity of your situation, and nobody has given you a framework for that.7 min readMetabolic healthThe history of obesity drugs — from amphetamines to OzempicIn 1933, a Stanford biochemist named Maurice Tainter published results showing that dinitrophenol — a yellow industrial chemical used in explosives and pesticides — produced dramatic weight loss by uncoupling the mitochondria, turning metabolic energy into heat instead of ATP. Within a year, an estimated 100,000 Americans were taking it. By 1938, it had killed enough people from hyperthermia, cataracts, and peripheral neuropathy that the newly empowered FDA used it as a case study for why drug regulation existed. The drug was pulled. The people who had sold it moved on to other things. The demand that had driven its adoption — the urgent, intractable desire for an effective treatment for obesity — did not go anywhere.8 min readMetabolic healthThe Ozempic moment — when a diabetes drug rewired the cultural conversation about weightLate 2022, something shifted. Elon Musk tweeted that he'd lost weight with Wegovy and fasting. A few weeks later, similar admissions began surfacing from entertainment and media figures who'd previously said nothing — or who had attributed the transformation to discipline and training. The script had been running for decades: public figures lost dramatic amounts of weight, credited hard work and the right salad, and nobody pressed too hard on the math. Then, suddenly, the math was on the table. The drug was real. The name was everywhere.8 min readOrigins and discoveryThe decades arc of peptide research — what's changed and what's recurredIn 1921, Frederick Banting was a twenty-nine-year-old Canadian surgeon with a research idea that his department chairman at the University of Toronto considered unpromising. The idea was that insulin — the pancreatic secretion that had been hypothesized for decades to regulate blood sugar — could be isolated and used to treat diabetic patients who would otherwise die. Banting had read a paper about the pancreatic islet cells and had a method in mind for isolating their secretion without contaminating it with the destructive enzymes produced by surrounding tissue. His chairman, J.J.R. Macleod, gave him a laboratory, a summer, a young biochemist named Charles Best, and a collection of experimental dogs. By the end of that summer, the extract worked in dogs. By January 1922, Leonard Thompson — a fourteen-year-old diabetic patient near death in Toronto General Hospital — received the first injection in a human being. By the end of the century, the compound that Banting and Best partially purified in that summer laboratory had been re-engineered through recombinant DNA technology, was being produced by bacteria carrying a human gene, and was keeping approximately nine million Americans alive.11 min readMetabolic healthPeptides for diabetes and blood sugar — the incretin revolution and beyondYou eat the sandwich and your energy crashes an hour later. Not dramatically — you don't lose consciousness, you don't shake. But there's a particular kind of slump, a fogginess that settles in, a craving for something sweet that doesn't quite match your hunger, and you find yourself in the afternoon with less to give than you should. Blood sugar dysregulation at its subclinical edges doesn't announce itself with crisis symptoms. It shows up as a pattern: the energy inconsistency, the difficulty losing weight despite reasonable effort, the fasting glucose trending upward at each annual physical, the waistline that keeps expanding regardless of what you do. And then one day a number crosses a threshold — fasting glucose over 100, HbA1c at 5.7 — and what was subclinical becomes a diagnosis.11 min readMetabolic healthPeptides for fat loss — what research has explored, by mechanismYou have done the things. You track what you eat. You work out. You drink water. And yet the number moves slowly if it moves at all, and the distribution of fat on your body seems indifferent to your effort in ways that feel not quite fair. The conventional answer is that you're not in a sufficient caloric deficit, and that may be technically true, but it sidesteps the part where caloric deficit is harder for some bodies than others — where hunger signals are different, where metabolic rates differ, where fat distribution is being regulated by hormonal signals you can't control with willpower.10 min readImmune modulationPeptides with chronic kidney disease — what changes when the kidneys aren't working at baselineYour creatinine has been creeping for three years. You're at stage 3b now, eGFR in the low forties, already on an ACE inhibitor and a statin, watching your potassium and phosphate at every appointment. You've read about GLP-1 agonists in the context of metabolic health and wondered if they apply to you. You've heard about peptides in various wellness contexts and wondered what, if any, of that conversation is relevant to someone whose kidneys are already compromised. Your nephrologist is focused on slowing the progression. The peptide conversation isn't one you've been able to have with her in any structured way.9 min readMetabolic healthSema vs Tirz vs Retatrutide — picking your incretinYou've been told there are options now. Your provider mentioned semaglutide, then mentioned tirzepatide, then someone in the waiting room mentioned something called retatrutide, and you left with three names written on your phone and no clear sense of which one is actually right for you. The differences are not cosmetic. The mechanism, the evidence base, the regulatory status, and the practical access path diverge in ways that matter — and chasing the highest weight-loss number from a clinical trial abstract is not the same as making the right decision for your specific situation.10 min readMetabolic healthSemaglutide vs. tirzepatide: how to actually decide between themYou've done enough research to know that both medications are weekly injectables, that both work through GLP-1, that both have produced results in trials that made headlines. And now you're at the actual decision point — which one, and why — and the information available online tends to either oversimplify it ("tirzepatide is stronger, tirzepatide wins") or hedge so thoroughly it says nothing useful. The honest answer is that it depends on specific things about you, and those things can be named.6 min read