Dr. Michael Fulks, Consulting Medical Director, discusses recent articles on several new obesity drugs that are hoped to be cheaper and more effective.
I have previously blogged on GLP-1 receptor agonists like semaglutide (Wegovy) which are the first effective, low risk (but high cost) drugs resulting in substantial ongoing weight loss. Sales have been brisk, but costs are high. Administration has required weekly injection although semaglutide will soon be available for weight loss as a daily pill taken (still inconveniently) ½ hour before any food or drink in the morning.
A recent news article in Nature by Saima Sidik updates things with discussion of two recent articles that appear in NEJM covering trials with new GLP-1 receptor agonists, retatrutide and orforglipron.
Retatrutide is a new peptide GLP-1 agonist also impacting other gut receptors in addition to GLP-1 further decreasing appetite and resulting in gradual weight loss. It appears to be more effective than semaglutide with an average weight loss at higher doses of almost 25% at 11 months with weight still decreasing at that point. It will likely be equally expensive and still require weekly injections but was effective for 100% of those assigned to the higher dose arms of the trial. It has similar GI side effects (nausea, vomiting and diarrhea) to other GLP-1 agonists requiring gradual dose escalation but for those with substantial obesity with or without DM, this could be a game changer and avoid the need for higher risk and even costlier bariatric surgery or the substantial health hazards associated with obesity and DM.
Orforglipron, on the other hand, may be slightly less effective than semaglutide but has a huge advantage in being a small non-peptide molecule allowing for easy oral use and much easier manufacturing which could result in substantial price reductions from the current $1,000 a month for semaglutide. This drug was still effective for over 90% of users with a mean weight loss at 9 months of 15% and still declining. Another non-peptide orally available drug, danuglipron, is in trials for DM but also generates weight loss.
When attempts at long term diet alteration and more exercise to treat obesity do not suffice (most of the time), these or other similar drugs still in the pipeline may be the next step and achieve widespread use. Control of cost and side effects are critical as treatment must be continued (perhaps at reduced dose) for weight loss to be maintained.
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.