It’s possible that tirzepatide is slightly more effective because it’s a dual receptor agonist. In addition to GLP-1, it also activates receptors for GIP, another hormone involved in regulating blood sugar and appetite. But McGuire says GIP isn’t well understood, and it’s not clear whether the addition of GIP is driving the greater weight loss or whether tirzepatide is simply better at activating GLP-1. “We just don’t have a way to tease out that biology right now,” he says.
That hasn’t stopped pharmaceutical companies from continuing to pursue GIP as a target. Viking Pharmaceuticals is also developing a drug that activates both the GLP-1 and GIP receptors. The San Diego company is testing both an injectable version and a pill. In a trial of the injectable version, participants They lost almost 15 percent of their weight for 13 weeks. And data published in March from an early-stage trial showed that people who took the daily pill version of Viking They lost about 5 percent of their weight. on average, in just one month.
New Nordisk, Eli Lillyand Pfizer They are all working on their own GLP-1 pills. Some patients may prefer to take a daily pill rather than a weekly injection. The pills are also easier to make than the injection pens used to administer Wegovy and Zepbound. The pens also need to be refrigerated.
“All of this makes these drugs more expensive,” said Laura Davisson, director of the weight management program at West Virginia University Health System. “If we could get oral versions on the market, maybe the prices would come down.”
Meanwhile, Amgen believes a less frequently taken drug could be convenient for some patients. The company is working on an injectable drug called MariTide that would be administered just once a month. The drug also acts on GLP-1 and GIP, but instead of stimulating GIP receptors, MariTide blocks them. It is not entirely clear Why both stimulation and blockage of these receptors appear to promote weight loss.
Amgen’s approach is based on research showing that mice lacking GIP, as well as people with mutations in this receptor, have lower body weight. Results published in FebruaryPeople taking MariTide in an early-stage trial lost up to 14 percent of their body weight in 12 weeks.
Eli Lilly hopes to create a drug even more potent than Zepbound by adding a third mechanism involved in weight loss. It is working on an investigational drug called retatrutide, which acts on GLP-1, GIP and glucagon receptors, the latter of which can help break down fat deposits. In the trial data published last yearRetatrutide helped participants lose more than 17 percent of their body weight, or 41 pounds, after 24 weeks. By 48 weeks, participants had lost an average of 24 percent of their body weight, or about 58 pounds — more than any other drug on the market.
“We’ve never seen results like this before in a trial of less than a year’s duration with an anti-obesity drug,” said Ania Jastreboff, an endocrinologist and weight specialist at the Yale School of Medicine during a press conference last year at the American Diabetes Association’s annual meeting.