Semaglutide, Tirzepatide, CagriSema, Oh My! Emerging Treatment Options for Obesity and Type 2 Diabetes
At ATTD 2023, a panel of experts discussed the latest medications for weight loss and the treatment of obesity. The panel highlighted two FDA approved drugs, as well as a promising combination therapy in development.
Although effective and safe treatments for obesity exist, weight loss medications are rarely prescribed for adults with obesity.
Part of the reason, according to Dr. Mojca Jensterle Sever of the University of Ljubljana, is that “obesity is still perceived as a lifestyle disease.” But because obesity is a disease that requires clinical intervention to provide meaningful benefits, medications should be considered in certain individuals.
A panel of experts at the ATTD 2023 conference in Berlin, Germany, discussed effective medications that can prevent and treat obesity. Semaglutide (Wegovy) and tirzepatide (Mounjaro) and the investigational combination of semaglutide and an amylin analogue (CagriSema) have shown impressive results in studies of people with obesity. Although semaglutide is approved for treatment of obesity, tirzepatide and CagriSema are still in clinical trials and not yet approved for obesity.
The STEP programme clinical trial further looked at the benefits of semaglutide such as delayed gastric emptying in women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, and obesity, as well as healthier eating habits, better portion sizes and overall less food cravings.
The GLP-1 medication semaglutide has been shown to be effective and safe across a broad population of people with overweight and obesity, leading to 10-20% weight loss which is usually needed to see the benefits. Specifically, semaglutide reduced total fat mass and visceral fat mass (generally considered to be unhealthy fat) and increased the proportion of lean body mass in adults with overweight or obesity.
The first goal in obesity treatment is to achieve weight loss but perhaps most importantly, individuals need to maintain that weight loss and prevent weight gain, said Jensterle. These medications should continue to be taken after weight loss to maintain a healthy weight.
Juan Frias, Medical Director of the National Research Institute in Los Angeles, discussed tirzepatide, a dual GIP/GLP-1 under investigation for people with obesity resulting in significant weight loss. Studies showed that 91% of people who took tirzepatide (at 15 mg) lost at least 5% of their weight and 57% of people achieved at least a 20% weight reduction after 72 weeks. The results show the promise that tirzepatide may hold if approved for people with obesity.
Additionally, the SURMOUNT-1 trial found that 95% of people with obesity who also had prediabetes and took tirzepatide reverted to normal glucose levels. People also experienced improvements in their fasting glucose, A1C, blood pressure, waist circumference, and normal levels of insulin while taking tirzepatide.
Dr. Julio Rosenstock, director of the Dallas Diabetes Research Center, expanded on the results of tirzepatide, explaining that the SURPASS-3 trial showed that it leads to greater time in range. Taking 15mg tirzepatide resulted in study participants achieving a 91% time in range compared to 75% with long-acting insulin.
CagriSema, under investigation for people with obesity as well as type 2 diabetes, has also shown weight loss (up to 15.6% reduction) as well as improved A1C (up to 2.18% reduction) in its phase 2 clinical trial. CagriSema is a combination medication that includes semaglutide and a drug called Cagrilintide. This means that it mimics the action of amylin, a hormone produced by the pancreas that makes people feel "satiety," or “fullness,” after eating a meal.
Ultimately, the panelists emphasized, obesity is not the result of lifestyle choices but rather a disease that requires clinical intervention and should be viewed as a treatable disease. The results that these drugs have achieved demonstrate the importance, and sometimes the necessity, of medication in treating obesity.
Additionally, these anti-obesity drugs “have moved the goalpost for type 2 diabetes and should be considered initial therapy, allowing to attain ‘diabetes reversal or remission’ which may no longer be the ‘impossible dream to reach,’” said Rosenstock.