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 unclear whether adding GIP promotes more weight loss or whether tirzepatide just works better at activating GLP-1. “We don’t have a way to decipher that biology right now,” he says.
That hasn’t stopped pharmaceutical companies from pursuing 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 injection and a pill form. In a trial of the injection version, participants lost nearly 15 percent of their weight over 13 weeks. And data released in March from an early-stage trial showed that people taking a daily pill version of Viking lost about 5 percent of their weight average just in one month.
Novo Nordisk, Eli LillyAnd Pfizer Company are all working on their own GLP-1 pills. Some patients may like to take medicine everyday via a weekly injection. The pills are also easier to manufacture than the pens used to inject Wegovy and Zepbound. The pens also need to be refrigerated.
“All of that makes these drugs more expensive,” said Laura Davisson, director of the weight management program at the West Virginia University Health System. “If we could bring oral versions to market, maybe the price would come down.”
Meanwhile, Amgen thinks a less-invasive drug could be convenient for some patients. The company is working on an injectable drug called MariTide, which is given only once a month. It also targets GLP-1 and GIP, but instead of stimulating the GIP receptor, MariTide blocks them. That’s not entirely clear Why does stimulating and blocking these receptors both seem to promote weight loss?
Amgen’s approach is based on research showing that mice lacking GIP as well as people with mutations in the receptor have lower body weights. In Results announced in FebruaryPeople taking MariTide in early-phase trials lost more than 14 percent of their body weight within 12 weeks.
Eli Lilly is hoping to create an even more powerful drug than Zepbound by adding a third mechanism involved in weight loss. The company is working on an experimental drug called retatrutide, which targets the receptors for GLP-1, GIP, and glucagon, the latter of which may help break down fat stores. In the trial data published last yearRetatrutide helped people lose more than 17 percent of their body weight, or 41 pounds, after 24 weeks. By week 48, 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 have never seen results like this in a trial of less than a year with an anti-obesity drug,” Ania Jastreboff, an endocrinologist and weight specialist at Yale School of Medicine, said in a press conference last year at the annual meeting of the American Diabetes Association.
