In the 1980s, Researchers identified a hormone in the human gut called GLP-1 that stimulates the release of insulin to control blood sugar levels, a discovery that ultimately led to a new class of diabetes drugs known as GLP-1 receptor agonists, the first of which was approved in 2005.
The drug doesn’t just keep blood sugar levels in check; interestingly, it also appears to suppress appetite, and some people who take it have experienced modest weight loss. This discovery led the U.S. Food and Drug Administration to approve the first GLP-1 drug for weight loss in 2014. Called liraglutide and sold under the brand name Saxenda, the once-weekly injection helped study participants lose an average of about 3 percent of their body weight.
At the time, Novo Nordisk, the manufacturer of Saxenda, was working on developing a better GLP-1. This new drug, semaglutide, was first approved as a diabetes treatment in 2017 under the brand name Ozempic, and then approved as a weight-loss drug in 2021 as Vigovy. In clinical trials for this drug, subjects given Vigovy lost about 15% of their initial body weight, which was quite a breakthrough.
Semaglutide will be followed by Eli Lilly’s tirzepatide, which is due for approval as the diabetes drug Munjaro in 2022 and the weight-management drug Zepbound in 2023. In a study of Zepbound, patients taking the highest dose lost about 21% of their weight. A head-to-head comparison of Wegoby and Zepbound published earlier this month found that Zepbound was more likely to lead to greater weight loss.
These drugs are now wildly popular and therefore in short supply, resulting in huge profits for the companies that manufacture them. The success of these drugs has created a frenzy among pharmaceutical companies searching for the next blockbuster weight loss drug. Researchers are now racing to develop new anti-obesity drugs that are more effective, more convenient, and have fewer side effects than those currently on the market. Existing drugs can cause unpleasant side effects such as nausea and headaches, causing some people to stop taking them.
There are other drawbacks, too. In the U.S., it can cost more than $1,000 a month and may not be covered by insurance. It must be injected subcutaneously once a week. While most people who stick with it see good results, some lose very little weight. Not to mention the lack of GLP-1 makes it difficult for patients to start and stick with it as prescribed.
More drugs on the market not only mean more choices for patients but also more profits for the companies that sell them. “It’s a very exciting and busy time in the field of obesity right now,” says Darren McGuire, a cardiologist and professor of internal medicine at the University of Texas Southwestern Medical Center.
Semaglutide and tirzepatide activate GLP-1 receptors in the pancreas to stimulate insulin production and control blood sugar levels in people with type 2 diabetes. The drugs also slow gastric emptying and interact with GLP-1 receptors in the brain to suppress hunger, which results in people eating less and having fewer food cravings while taking them.
Tirzepatide may work a little better because it’s a dual receptor agonist; in addition to GLP-1, it activates receptors for GIP, another hormone involved in regulating blood sugar and appetite. But Maguire says GIP is not well understood, and it’s unclear whether adding it helps increase weight loss or whether tirzepatide is just better at activating GLP-1. “We don’t have a way to figure out the biology of it right now,” he says.
