New Drugs May Treat Obesity


On May 13, 2022, the U.S. Food and Drug Administration approved tirzepatide (Mounjaro), from Lilly, for the treatment of type 2 diabetes. The drug has not been approved for weight loss, but so far studies show that tirzepatide with a weight loss diet causes significant weight loss in diabetics and sent 50 percent of them into remission as long as they kept taking the drug. The most recent study found that 63 percent of 2,539 obese, non-diabetic adults who were put on a weight loss diet and received tirzepatide once a week achieved at least 20 percent body weight reduction in 72 weeks (NEJM, June 4, 2022). The patients were given either 0, 5, 10, or 15 mg of tirzepatide per day, and those given:
• 5 mg lost an average of 35 pounds
• 10 mg lost an average of 49 pounds
• 15 mg lost an average of 52 pounds
Patients receiving placebo injections lost an average of five pounds.

Higher doses of tirzepatide led to more weight loss, but they caused more side effects, mainly nausea, diarrhea, vomiting, and constipation. Other studies report similar weight loss with this class of drugs (Diabetes Obes Metab, Jun 2020;22(6):938–946). Similar drugs such as semaglutide are restricted to a maximum of two years, not to be repeated.

How These Drugs Work
These drugs mimic two hormones called GLP-1 and GIP that our bodies naturally release after a meal to help regulate appetite and food intake by making us feel full. They stimulate the body to secrete more insulin and less glucagon, which help lower blood sugar levels and are involved in sending fullness signals from the gut to the brain. You eat less, and people who take the drug often find that when they eat too much food, the food comes back up. This can lead to the most common side effects: nausea, vomiting, diarrhea and stomach cramps. A variety of other side effects and cautions are also listed, including low blood sugar levels. However, the risk of low blood sugar levels is usually only increased if the person is taking another medication known to lower blood sugar at the same time, such as sulfonylureas or insulin.

Other type II diabetes drugs in the GLP-1 agonists class include:
Dulaglutide (Trulicity), taken by injection weekly
Exenatide extended release (Bydureon), taken by injection weekly.
Exenatide (Byetta), taken by injection twice daily.
Semaglutide (Ozempic), taken by injection weekly.
Semaglutide (Rybelsus), taken by mouth once daily.

My Recommendations
Diets and food restrictions often fail miserably to control obesity. These recent studies on tirzepatide seem to show that GLP-1 agonists may help to control overweight when combined with a sensible calorie-restricted diet. If more studies show similar success rates and do not raise serious safety concerns, I expect that these drugs will soon be approved for use on general weight loss, without limiting them to diabetics. They are likely to be very expenive.