An experimental drug being clinically investigated for its effects on body weight in obese and overweight people has delivered record-breaking weight loss for participants in the trial – on par with surgical options, the company behind the drug suggests. Tirzepatide, developed by American pharmaceutical company Eli Lilly and Company (Lilly), is a once-weekly injection that promotes weight loss by mimicking the effects of natural hormones called incretins. These hormones lower blood sugar after we eat, in addition to regulating metabolic processes related to digestion. In the case of tirzepatide, which is not yet available on the market pending further clinical study, the drug is a synthetic combination of two particular incretins, called GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). The former hormone, GLP-1, is the basis of the anti-diabetes medication semaglutide, which was approved in the US as a weight-loss drug in 2021, representing the first time the FDA had endorsed a new treatment for weight loss in several years. That approval was granted on the back of results described as a 'game-changer' for weight loss, but it looks like tirzepatide's formulation – thanks to the addition of GIP alongside GLP-1 – might well change the game again. In Phase 3 results from the ongoing SURMOUNT–1 clinical trial investigating the effects of tirzepatide, researchers enrolled 2,539 participants who were either overweight or obese (with one weight-related comorbidity but without type 2 diabetes). The participants received tirzepatide or a placebo over the course of 72 weeks, along with support to follow a reduced-calorie diet and increase their levels of physical activity. Tirzepatide was administered at one of three different doses (either 5, 10, or 15 milligrams in the weekly injection), but all three groups saw significant levels of weight loss over the course of the study. On the highest dose (15 mg), participants saw average weight reductions of 22.5 percent of their body weight (24 kg or 52 lb), while the 10 mg dose achieved 21.4 percent weight loss (22 kg or 49 lb), and 5 mg saw a 16 percent body weight reduction (16 kg or 35 lb). By comparison, the placebo group lost only 2.4 percent of their body weight (2 kg or 5 lb). Previously, the semaglutide weight loss trials averaged a roughly 17 percent weight loss. "Tirzepatide is the first investigational medicine to deliver more than 20 percent weight loss on average in a phase 3 study," says clinical research physician Jeff Emmick, the vice president of product development at Lilly. While the results have not yet been peer-reviewed, Lilly says they will be submitted for such consideration in the future. Meanwhile, study in the SURMOUNT-1 trial is ongoing, alongside related SURMOUNT trials, the results of which are expected to be announced in 2023 However, we do already know that tirzepatide does not agree with everyone who takes it. While the averaged weight-loss results do appear to slightly outperform treatment with semaglutide, and are about on par with the weight loss patients might expect from bariatric surgery, some participants in the tirzepatide arm experienced adverse effects. Depending on dose, up to one-third of the group on tirzepatide experienced nausea, while diarrhea was also relatively common (for 18.7–23 percent of participants). Some people also experienced vomiting and constipation, although it's worth noting only a small percentage of participants left the study due to these effects. Yet another potential barrier to stomaching tirzepatide is the issue of price – assuming subsequent research results convince the FDA to approve the drug for weight-loss patients, that is. (The drug has already been submitted for regulatory review for diabetes treatment.) As others have noted, semaglutide – sold as a weight-loss drug under the brand-name Wegovy by Danish pharmaceutical company Novo Nordisk – sells for over US$1,300 per month, and very few patients can afford such an expensive medication, especially when drugs like this are rarely covered by health insurance. If tirzepatide follows a similar pricing strategy – upon its expected but not-yet-assured future release – this could be another case of a potentially brilliant, life-changing medication that many people sadly won't be able to buy. "The drugs themselves appear to be great, but Wegovy is expensive, and the others probably will be too," neuroscience and obesity researcher Stephan Guyenet told Gizmodo. "This is especially true in the US, where Wegovy costs about four times more than in other countries. So the main question becomes one of access." Aside from the economics, the impressive results of these medications nonetheless suggest we might soon be able to transform the treatment of obesity – a complex and harmful epidemic that has resisted our control for decades. If we can realize that promise, and ensure equitable access to this new generation of obesity medications, we stand to improve the health of millions of people around the world, researchers say. "This is extremely exciting, albeit preliminary data showing bariatric surgery-level weight loss from a medication, one that likely affords numerous other metabolic benefits," Scott Kahan, the director of the National Center for Weight and Wellness in Washington, DC, told Healio. "Continued development of tirzepatide and similar agents could portend a sea change in obesity treatment, similar to how cholesterol and heart disease management was transformed by the advent of statin medications and how HIV management was transformed by antiretroviral medications." Source
