A Weekly Shot for Type 2 Diabetes Yields Long-Term Weight Loss
Dr. Michael Fulks comments on drugs targeted for weight loss in patients with type 2 diabetes.
Last year we blogged about semaglutide, a GLP-1 receptor agonist, originally approved as an Rx for type 2 diabetes mellitus (DM) as a highly effective treatment for obesity when given subcutaneously on a weekly basis. Called Wegovy, the drug was quickly approved for weight loss at BMI of 27+ if associated with a complication like DM, hypertension, or a BMI 30+.
Now, there is a similar drug called tirzepatide (Mounjaro), a GLP-1 agonist that is already approved for type 2 diabetes and has additional GIP agonism as well. Both agonists increase insulin release and reduce glucagon secretion, which explains their effectiveness against DM but not weight loss. What we do know is that GLP-1 agonists delay gastric emptying and increase satiety as well as affecting adipose metabolism. GIP agonists also appear to have direct CNS actions on appetite.
An article published in the New England Journal of Medicine on a 72-week study of tirzepatide for weight loss was conducted in a similar manner to the earlier semaglutide weight loss study. Participants were two-thirds female without type 2 diabetes and an average age of 45 and weight of 230 pounds (BMI 38). The results are nothing less than astounding. At the higher dose levels (10 or 15 mg weekly), the mean weight loss was approximately 20% with a 34% reduction in fat mass. The weight loss probably exceeded that shown for semaglutide and was associated with an almost 90% trial completion rate for the active treatment arm. Chief side effects are nausea, diarrhea, and constipation, which typically resolved after the initial 20-week dose escalation period, and rarely caused participants to discontinue treatment.
Tirzepatide will almost certainly be approved soon for weight loss, probably with BMI requirements like those for semaglutide, as it is both a safe and highly effective drug. Unfortunately, each of these drugs is likely to cost >$10,000 a year. Both future FDA approval – which impacts insurance coverage – and patient acceptance for even lower BMIs is unclear, but I expect wide use given that currently >40% of adults in the US have a BMI ≥30 and type 2 diabetes is epidemic. Now, if we could only reduce the cost of this drug class, we might make a bigger dent in the #1 health problem in the US.
About the Author
Michael Fulks, MD, Consulting Medical Director, is board-certified in internal and insurance medicine. After leaving practice, he served as a medical director, creating or editing several underwriting manuals and preferred programs. More recently, Mike has consulted for CRL participating in its mortality research on laboratory test results, BP and build, and in the development of risk-scoring tools for laboratory and non-laboratory data.