After the weight loss injection semaglutide, a second active ingredient originally approved for diabetics is now also showing great effectiveness against obesity: tirzepatide. This drug combines chemical components of two intestinal hormones that affect satiety and sugar metabolism. In a phase 3 clinical study, severely overweight test subjects achieved a reduction in body weight of around 26.6 percent after twelve weeks of an introductory diet and lifestyle changes and 72 weeks of taking tirzepatide; the pure weight loss in the tirzepatide phase was 18 .4 percent. Blood counts and blood pressure also improved more in the tirzepatide group than with a placebo. According to the team, this confirms that people with obesity can significantly lose weight and thus improve their health with this type of medication.
People who are very overweight and obese often find it difficult to lose weight permanently. The reasons for this are not only a lack of diet discipline, but also biological factors. Studies suggest that the hormonal control of hunger and satiety is out of balance in people who are very overweight. The changed intestinal flora of those affected could also help to increase appetite and promote the yo-yo effect. “The renewed weight gain after a diet and lifestyle change is partly due to ongoing adjustments to the metabolism, through which the hunger hormones of those affected increase and the satiety hormones decrease,” explain Thomas Wadden from the University of Pennsylvania and his colleagues. “Energy consumption also decreases disproportionately in relation to weight loss.” As a result, it is more difficult for people who are very overweight to burn additional calories, for example through exercise.
Tirzepatide mimics two intestinal hormones
In recent years, however, it has been shown that some active ingredients originally developed to combat type 2 diabetes can at least partially break this vicious circle. These drugs, including the active ingredient semaglutide, which is approved under the drug names Ozempic and Wegovy, mimic the body's own intestinal hormone that influences sugar metabolism and the feeling of satiety. This glucagon-like peptide-1 (GLP-1) acts on both the insulin-producing cells in the pancreas and the brain, helping to regulate hunger and blood sugar levels. Clinical studies have shown that obesity patients lose weight steadily and sustainably with this “weight loss injection” – at least as long as the active ingredient is injected once a week. The current study focused on another, more advanced active ingredient: tirzepatide not only mimics the effect of the GLP-1 messenger, but also that of a second intestinal hormone, the glucose-dependent insulinotropic peptide (GIP).
In previous studies, this combined effect led to a weight reduction of a good 20 percent in 72 weeks - more than with semaglutide. Tirzepatide under the trade name Mounjaro is already approved for the treatment of type 2 diabetes in the USA and the EU, and approval for the treatment of obesity is in progress. Wadeen's team has now investigated whether tirzepatide's weight loss success can be increased if it is combined with a diet and consistent lifestyle changes. To do this, the 806 participants initially underwent a classic diet for twelve weeks, during which they received intensive advice and instructions on how to change their lifestyle. Those who stayed after this preparation phase and who lost at least five percent of weight during these three months were allowed to take part in the next study phase, which lasted 72 weeks. In this test, half of the test subjects received a placebo, the other half received a dose of tirzepatide once a week, which was gradually increased from the initial 2.5 milligrams to 10 to 15 milligrams. Neither participants nor researchers knew who would get what.
26.6 percent weight loss after 84 weeks
After a total of 84 weeks, it was found that the test subjects who had received tirzepatide had lost an average of around 21.5 kilograms in weight, which corresponds to around 26.6 percent of their initial body weight. Of this, around 18.4 percent occurred in the study phase with weekly tirzepatide administration. On average, over the entire study period, the BMI decreased by almost eight points and the waist circumference by 14.6 centimeters. The test subjects in the placebo group, however, only lost weight by 3.8 percent over the course of the study, as Wadden and his team report. Similar to the other preparations, tirzepatide mainly caused side effects in the digestive tract, including nausea, diarrhea or constipation. They mainly occurred when the dose of the active ingredient was increased and then subsided again.
“These results provide solid evidence that tirzepatide is not only an effective therapy for people with type 2 diabetes, but also helps effectively achieve significant, life-changing weight loss when combined with calorie-restricted diet, exercise and counseling,” says Co -Author Gitanjali Srivastava of Vanderbilt University. Similar to previous studies on tirzepatide, the weight loss achieved with the active ingredient was significantly higher than that achieved with GLP-1 active ingredients such as semaglutide. This confirms that the mimicking of the intestinal hormones GLP-1 and GIP associated with tirzapatide has a greater weight-promoting effect. “These new therapies are rapidly changing the field of obesity treatment – and more are already in development,” says Srivastava. Both semaglutide and tirzepatide offer people who are very overweight the chance to lose weight better and more efficiently than with diets and common methods alone.
Source: Thomas Wadden (University of Pennsylvania, Philadelphia) et al., Nature Medicine, doi: 10.1038/s41591-023-02597-w