Semaglutide, the active ingredient in Ozempic, has been studied in humans since 2014, with its scientific roots stretching back to the mid-1980s. The drug received FDA approval in December 2017, and large-scale trials have continued well beyond that point, meaning researchers now have roughly a decade of clinical trial data and over seven years of real-world use to draw from.
The Science Behind Ozempic Started in 1986
Ozempic belongs to a class of drugs that mimic a gut hormone called GLP-1, which helps regulate blood sugar and appetite. The foundational discovery happened in September 1986, when researchers published findings showing that this hormone is produced in the intestine. By early 1987, scientists had demonstrated that GLP-1 potently stimulates insulin secretion, boosting it six-fold at concentrations that naturally circulate in the body.
Those discoveries launched decades of drug development. The first commercial GLP-1 drug, exenatide (Byetta), reached the market in 2005. Novo Nordisk, the company behind Ozempic, developed liraglutide (a daily injectable GLP-1 drug) around 2000 and then refined the molecule further to create semaglutide, which lasts long enough in the body to be injected just once a week. While the exact year semaglutide was first synthesized isn’t publicly documented, it entered human clinical trials in 2014.
Clinical Trials Ran From 2014 Through FDA Approval
Ozempic’s path to approval was built on a series of clinical trials called the SUSTAIN program. SUSTAIN 1, the first major trial, enrolled its first participants in February 2014 and completed in May 2015. It tested semaglutide against a placebo in people with type 2 diabetes who weren’t yet taking other diabetes medications.
The SUSTAIN program expanded to include seven trials in total, each comparing semaglutide against different existing treatments or testing it in different patient populations. These trials collectively enrolled thousands of participants and measured both blood sugar control and safety over periods ranging from 30 weeks to about two years. Based on this body of evidence, the FDA approved Ozempic on December 5, 2017, for improving blood sugar levels in adults with type 2 diabetes.
A Two-Year Cardiovascular Safety Trial
One of the most important studies in the SUSTAIN program was SUSTAIN 6, a dedicated cardiovascular outcomes trial. This trial enrolled 3,297 people with type 2 diabetes who were at high risk for heart attacks and strokes. Participants were followed for up to 109 weeks (roughly two years), making it one of the longer semaglutide studies completed before approval.
The trial was “event-driven,” meaning it was designed to run until enough cardiovascular events (heart attacks, strokes, or cardiovascular deaths) occurred to draw statistically meaningful conclusions. The results showed that semaglutide not only didn’t increase heart risk but actually reduced it, which became a significant selling point for the drug and set the stage for even larger cardiovascular studies.
The SELECT Trial Extended the Evidence Further
After Ozempic reached the market, Novo Nordisk launched an even more ambitious study called SELECT. This randomized, double-blind trial enrolled 17,604 patients across 41 countries between October 2018 and March 2021. Unlike earlier trials focused on diabetes, SELECT studied semaglutide in people with obesity and existing cardiovascular disease, regardless of whether they had diabetes.
SELECT tracked major cardiovascular events including heart attacks, strokes, cardiovascular death, and hospitalizations for heart failure. The trial’s results, published in The Lancet, confirmed that semaglutide reduced the risk of these events compared to placebo. This trial represents some of the longest controlled data available on semaglutide, with participants followed for several years after enrollment began in 2018.
Real-World Data Since 2018
Beyond controlled clinical trials, researchers have also tracked how Ozempic performs in everyday medical practice. The SURE program, a series of real-world observational studies, followed adults with type 2 diabetes who were prescribed semaglutide by their regular doctors rather than enrolled in a controlled experiment. These studies ran for approximately 30 weeks each and provided safety and effectiveness data from routine clinical settings, where patients often have more complex health profiles than those in tightly controlled trials.
Since Ozempic launched commercially in early 2018, millions of prescriptions have been written worldwide. This real-world exposure has given regulators and researchers a growing body of post-marketing safety data spanning more than seven years. Adverse event reporting systems continue to collect information on side effects and rare complications that may not have appeared in the original trials.
How This Compares to Other Medications
A decade of clinical trial data is substantial for any prescription drug. Most medications reach the market with three to seven years of human trial data, then rely on post-marketing surveillance to catch rare or long-term effects. Semaglutide’s evidence base is now larger than what many drugs accumulate in their first decade, partly because of the massive SELECT trial and the intense scientific interest in GLP-1 drugs for both diabetes and weight loss.
That said, the use of Ozempic and similar drugs for long-term weight management is newer territory. The weight-loss formulation, Wegovy (which contains a higher dose of the same molecule), was approved in June 2021. Questions about what happens when people take these drugs for five, ten, or twenty years are still being answered in real time, as no controlled trial has yet followed semaglutide users for that long.