The adverse effects of obesity on physical health, as well as the benefits of weight loss, are well known. Losing 5-10% of your body weight can reduce the risk of type 2 diabetes while also improving cardiometabolic risk factors (such as hypertension) and other obesity-related complications (such as osteoarthritis).
Intensive lifestyle intervention is recommended as a way to manage obesity, including reducing caloric intake and increasing exercise. But its overall effectiveness is limited by two factors. First, the weight loss effect of lifestyle intervention is average, with less than 20% of people able to lose more than 15% of their weight. Second, weight loss achieved through lifestyle intervention usually restores one-third of the body weight within a year and gradually recovers over time.
In recent years, new weight loss drugs based on GLP-1 receptor agonists have been approved for marketing, which can support the results of intensive lifestyle intervention. Semaglutide is a GLP-1 receptor agonist developed by Novo Nordisk and has been approved for the control of type 2 diabetes and weight loss. In people who are obese or overweight but do not have diabetes, semaglutide can reduce body weight by 15% over up to 2 years (compared to 2-3% for placebo). Semaglutide reduces appetite primarily by altering hunger and satiety signals in specific neural areas, thereby reducing caloric intake.
Tizepatide is a new drug developed by Eli Lilly and Company. It is a dual combination of glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor. Agonists that produce synergistic effects on appetite, caloric intake, and metabolic function. It has been approved for the control of type 2 diabetes in the United States, the European Union, Japan and other regions, and is being reviewed for use as a weight loss drug.
Results from a phase 3 clinical trial called SURMOUNT-1 released last year showed that people who were obese or overweight but did not have diabetes lost 20.9% of their body weight (placebo) after 72 weeks of treatment (15 mg injections once a week). 3.1% in the drug group), accompanied by a reduction in cardiometabolic risk factors.
The expert team suggests that using weight loss drugs after intensive lifestyle intervention can induce additional weight loss or at least prevent weight regain.
On October 15, 2023, Eli Lilly and Company, together with scientific research teams from the University of Pennsylvania and other research institutions, published a paper in the top international medical journal Nature Medicine entitled: Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT- Phase 3 clinical research paper of phase 3 trial.
Results from the phase 3 clinical trial, SURMOUNT-3, showed that treatment with Tizepatide for 72 weeks was followed by 12 weeks of intensive lifestyle intervention, including a low-calorie diet, exercise and frequent counseling. Over a total of 84 weeks, participants who were obese or overweight but did not have diabetes lost an average of 26.6% (29.2kg) of body weight, compared with only 3.8% (4.1kg) in the placebo group.
In the phase 3 clinical trial, SURMOUNT-3, a total of 806 participants, who started with an average weight of 109.5 kg, were obese or overweight adults without diabetes in a 12-week pilot lifestyle intervention. At the end of the period, which included a low-calorie diet, exercise and frequent counseling, 579 participants had lost 5% or more of their body weight. They had lost an average of 6.9% (7.6kg) of their body weight. They were then randomly assigned to receive either placebo or Tizepatide treatment lasted for 72 weeks, with a starting dose of 2.5 mg and increasing by 2.5 mg every four weeks until the maximum tolerated dose (10 mg or 15 mg) was reached.
Results showed that participants lost an average of 21.1% of their weight during 72 weeks of Tizepatide treatment. And they lost an average of 26.6% (29.2 kg) of body weight in the total 84 weeks since the start of the study. This is also the best drug weight loss effect currently achieved in clinical trials. The placebo group lost an average of 26.6% in weight during the 84 weeks. 3.8% lighter (4.1 kg).
The overall safety profile of Tizepatide in this Phase 3 clinical trial was similar to previous clinical trial results. The most common adverse events were gastrointestinal related and were generally mild to moderate in severity. Compared with placebo, the most common adverse events in the Tizepatide treatment group were nausea (39.7% vs. 14.0%), diarrhea (31.0% vs. 9.2%), constipation (23.0% vs. 6.8%), COVID -19 (23.0% vs. 25.3%) and vomiting (18.1% vs. 1.4%). Adverse events led to discontinuation of study treatment in 10.5% of participants in the Tizepatide group and 2.1% of participants in the placebo group.
Dr. Jeff Emmick, senior vice president of product development at Eli Lilly and Company, said that in this study, people who took Tizepatide after the intervention felt more significant and longer-lasting improvements in their relationship with diet and exercise than those who took a placebo after the intervention. weight loss. While intensive lifestyle intervention is an important component of obesity management, this clinical trial results highlight the difficulty some people have in maintaining weight loss with diet and exercise alone.
