Semaglutide
Based on Wikipedia: Semaglutide
In the summer of 2023, something remarkable happened in American medicine. A diabetes drug became the bestselling medication in the country—not because diabetes rates had suddenly spiked, but because millions of people had discovered it could help them lose weight. The drug was semaglutide, and its annual sales hit $38.6 billion, making it the most lucrative pharmaceutical product in the United States.
You've probably heard of it by its brand names: Ozempic and Wegovy.
But the story of semaglutide begins not in a boardroom focused on quarterly earnings, but in research labs decades ago, where scientists were puzzling over a hormone that seemed to hold the key to how our bodies regulate blood sugar and appetite.
The Hormone That Started It All
In the 1970s, two researchers named Jens Juul Holst and Joel Habener were studying something that might seem unrelated: duodenal ulcers. They wanted to understand the hormones our digestive system releases when we eat. Their approach was decidedly hands-on—they tested various hormones on pig pancreases to see what would happen.
What they discovered in 1988 changed everything. One hormone, glucagon-like peptide-1 (GLP-1), turned out to be extraordinarily potent. When released after eating, this hormone does several things at once. It tells your pancreas to release more insulin, which helps shuttle sugar from your blood into your cells. It tells your liver to stop releasing stored sugar. And crucially, it signals to your brain that you're full.
Think of GLP-1 as your body's natural "I've had enough" signal.
The implications for diabetes treatment were obvious. Type 2 diabetes occurs when your body either doesn't produce enough insulin or doesn't respond to it properly. If scientists could somehow enhance or mimic GLP-1's effects, they might be able to help diabetic patients control their blood sugar more effectively.
By 1993, a researcher named Michael Nauck had successfully infused GLP-1 directly into people with type 2 diabetes. The results were promising—blood sugar levels normalized. But there was a problem. Natural GLP-1 breaks down in the body within minutes. Treating diabetes would require constant infusions, which was impractical. And the side effects were significant.
Scientists needed to find a way to make GLP-1 last longer in the body.
Engineering a Better Molecule
The Danish pharmaceutical company Novo Nordisk took on this challenge. In 1998, a team led by Lotte Bjerre Knudsen developed liraglutide, the first practical GLP-1 receptor agonist—a molecule that activates the same receptors that natural GLP-1 does, but sticks around much longer. The term "receptor agonist" simply means a substance that binds to a receptor and triggers a response. It's like having a key that fits a lock and opens the door.
Liraglutide was a breakthrough, but Novo Nordisk's scientists weren't finished. A team including Jesper Lau, Thomas Kruse, and Paw Bloch set out to create an even better version.
Their creation, semaglutide, is a masterpiece of molecular engineering. The researchers took the structure of natural GLP-1 and made precise modifications to overcome its limitations.
First, they removed the first six amino acids—the building blocks of the hormone—because those aren't essential for function. Then they made two strategic substitutions. At one position, they replaced an amino acid called alanine with something called 2-aminoisobutyric acid. This seemingly minor change prevents an enzyme called dipeptidyl peptidase-4 from breaking down the drug. It's like adding a protective shield.
The cleverest modification came at another position, where they attached a long chemical chain ending in eighteen carbon atoms and a carboxyl group. This chain does something ingenious: it makes the drug molecule stick to albumin, a protein that circulates throughout your bloodstream for extended periods.
The result? While natural GLP-1 disappears from your system in minutes, semaglutide has a half-life of about seven days. You can take it once a week instead of constantly.
From Laboratory to Pharmacy
Clinical trials for semaglutide as a diabetes treatment began in June 2008. The evidence was compelling enough that in December 2017, the United States Food and Drug Administration (FDA) approved the injectable version under the brand name Ozempic for people with type 2 diabetes.
The approval was based on seven clinical trials involving over 4,000 participants across 33 countries. Some trials compared semaglutide to a placebo—an inactive injection—while others compared it to existing diabetes medications. The measure of success was HbA1c, a blood marker that reflects average blood sugar levels over the previous two to three months. Semaglutide consistently outperformed the alternatives.
But the most exciting finding came from a separate trial of nearly 3,300 participants with type 2 diabetes who were at high risk for cardiovascular problems. Over two years, those taking semaglutide had fewer heart attacks, strokes, and episodes of severe chest pain than those taking a placebo. This was significant because cardiovascular disease is the leading cause of death among people with diabetes.
Meanwhile, researchers noticed something intriguing in the trial data. Participants taking semaglutide were losing weight. Significant amounts of weight.
The Weight Loss Revolution
In March 2021, a pivotal trial was published. Nearly 2,000 adults with obesity—defined as a body mass index of 30 or higher—were randomly assigned to receive either semaglutide or a placebo injection once weekly, alongside lifestyle counseling about diet and exercise.
The results were stunning. After 68 weeks, people taking semaglutide had lost an average of 14.9 percent of their body weight. The placebo group lost just 2.4 percent. For someone weighing 200 pounds, that's the difference between losing about 30 pounds and losing less than 5.
In June 2021, the FDA approved a higher-dose version of semaglutide under the brand name Wegovy specifically for weight management. It was the most effective anti-obesity medication ever approved, though still less effective than bariatric surgery—procedures like gastric bypass that physically alter the digestive system.
How does a diabetes drug cause such dramatic weight loss? The mechanism is elegant. Semaglutide works on your brain's appetite centers, reducing hunger. It slows the emptying of your stomach, so you feel full longer. And it may alter the reward pathways that make us crave certain foods.
There's a catch, though, and it's an important one. When people stop taking semaglutide, the weight tends to come back. Studies show that within a year of stopping the drug, people regain about two-thirds of the weight they lost. This suggests that for many people, semaglutide isn't a one-time treatment but potentially a lifelong commitment.
The Side Effects
The most common side effects of semaglutide read like a list of digestive complaints: nausea, vomiting, diarrhea, constipation, and abdominal pain. For many people, these are most pronounced when starting the medication or increasing the dose, and they often diminish over time. Some also experience headaches, fatigue, dizziness, and heartburn.
But there are more serious concerns.
Gastroparesis—a condition where the stomach empties too slowly—has been linked to GLP-1 medications. Among people prescribed these drugs, about 0.1 percent were diagnosed with gastroparesis at least six months later. That might sound tiny, but it represents a 52 percent increased risk compared to people not taking these medications. Bowel obstruction is another documented risk.
The most ominous warning appears in a black box on the US prescription label—the FDA's strongest caution. In laboratory studies, semaglutide caused thyroid tumors in rodents. It remains unknown whether it has the same effect in humans, but the drug is contraindicated—meaning it should not be used—in people with a personal or family history of medullary thyroid carcinoma or a rare condition called multiple endocrine neoplasia type 2.
There have been suspicions about pancreatitis, an inflammation of the pancreas that can be serious or even life-threatening. However, a comprehensive review of studies published in 2019 did not find a significantly elevated risk.
A Pill Instead of a Shot
For many people, the idea of injecting themselves weekly is unappealing. Novo Nordisk addressed this by developing an oral form of semaglutide, which the FDA approved in September 2019 under the brand name Rybelsus for diabetes treatment.
Getting a peptide drug to work as a pill is remarkably challenging. Peptides are essentially small proteins, and your digestive system is specifically designed to break down proteins. The oral version of semaglutide uses a special absorption enhancer to protect the drug and help it pass through the stomach lining into the bloodstream.
In December 2025, the FDA approved an oral version of Wegovy for weight management, giving people who dislike injections another option.
Expanding Indications
As more data accumulated, the FDA expanded what semaglutide could be prescribed for. In March 2024, Wegovy was approved to reduce the risk of heart attacks, strokes, and cardiovascular death in adults with heart disease who are obese or overweight. A large trial of over 17,600 participants had shown that cardiovascular events occurred in 6.5 percent of those taking semaglutide compared to 8 percent taking a placebo—a meaningful reduction.
In August 2025 came another expansion. The FDA approved Wegovy for metabolic-associated steatohepatitis (MASH), a liver condition previously known as nonalcoholic steatohepatitis. In MASH, fat accumulates in the liver and causes inflammation and scarring. Left untreated, it can progress to cirrhosis or liver failure. There have been few effective treatments, making semaglutide's approval significant for people with moderate to advanced liver fibrosis.
The Economics of a Blockbuster Drug
With annual US sales of $38.6 billion in 2023, semaglutide became a pharmaceutical phenomenon. But that success created access problems.
In the United States, Wegovy carries a list price of about $1,349 per month. Ozempic costs around $936 monthly. These prices put the medication out of reach for many people who might benefit from it, particularly those without comprehensive insurance coverage. As one analysis noted, the people who could most benefit from weight loss may be unable to afford these expensive drugs.
The pricing disparity across countries is stark. The same one-month supply of Ozempic that costs $936 in the US costs $169 in Japan, $147 in Canada, and $144 in Switzerland.
High demand and limited supply led the FDA to declare shortages of Ozempic and Wegovy starting in August 2022. This shortage opened a door for compounding pharmacies—specialized facilities that can legally prepare custom versions of drugs on the FDA's shortage list.
But the compounding market became problematic. Novo Nordisk has taken action against pharmacies producing versions with impurities, incorrect amounts of active ingredient, or even no active ingredient at all. Some compounders have used salt forms of semaglutide—like sodium semaglutide or semaglutide acetate—in an attempt to circumvent patents on the base compound. These variants haven't been evaluated by the FDA for safety or effectiveness.
The situation grew more dangerous when counterfeit Ozempic pens appeared. In October 2023, fake pens surfaced in Europe, possibly containing insulin instead of semaglutide. Several people were hospitalized with hypoglycemia—dangerously low blood sugar—and seizures after using them. The FDA issued its own warning about counterfeits in the US in December 2023.
The Patent Horizon
Like all drugs, semaglutide's patent protection has limits. In Canada, the patent expired at the beginning of 2026—actually sooner than scheduled because Novo Nordisk failed to pay a required maintenance fee. In Brazil, the Supreme Court refused to extend the patent beyond 2026.
China's situation is more complex. A court ruled in 2022 that all patents on semaglutide were invalid there. Novo Nordisk appealed.
In the United States, Europe, and Japan, the core patents are expected to last until December 2031. When they expire, generic versions will likely flood the market, dramatically reducing prices—much as happened with blockbuster drugs like Lipitor and Prozac before.
Until then, semaglutide remains expensive, popular, and consequential. It represents both a genuine medical advance and a case study in pharmaceutical economics. The drug works—there's no question about that. But the question of who gets access to it, and at what cost, remains very much unresolved.
The Scientists Who Made It Possible
In 2021, the Warren Alpert Foundation Prize—a prestigious award for biomedical research—went to Jens Juul Holst, Joel Habener, and Daniel J. Drucker for their foundational work on GLP-1. Their decades of research, beginning with those pig pancreas experiments in the 1970s, ultimately transformed how we treat both diabetes and obesity.
It's a reminder that medical breakthroughs rarely happen overnight. The path from understanding a hormone's basic biology to having a medication that helps millions of people spans generations of scientific work. Semaglutide is the product of curiosity-driven research, careful molecular engineering, rigorous clinical trials, and regulatory navigation.
Whether you see it primarily as a medical triumph, an economic phenomenon, or a complex mix of both, semaglutide has undeniably changed the landscape of metabolic medicine. For better or worse, it's likely only the beginning of a new era in how we think about treating conditions that affect hundreds of millions of people worldwide.