The downside of semaglutides

GLP-1-based therapies for obesity have been transformational. The benefits are undeniable, and the risks for most people are negligible. These drugs belong in the class with anti-hypertensives and statins. Who could complain?

Here's one doc who was an initial enthusiast, but who has cooled:

“The truth is, most patients don't stay on anti-obesity medications -- I see it in my practice every day. Research shows that three-quarters of patients stop GLP-1 medications within 2 years, many within months. Reasons for discontinuation include cost, side effects, and supply shortages. But one of the most common reasons is that patients simply don't want to take a weight loss medication indefinitely. Many believe they can "beat the system," use them briefly, change their lifestyle, and stop taking them without regaining weight.

“Unfortunately, they can't. Clinical trials of semaglutide and tirzepatide show that the average patient regains two-thirds of the weight lost (and similar changes in cardiometabolic variables) within the first year of discontinuation. For some, the return of weight feels almost instantaneous, and they often regain more than they initially lost. My patients describe feeling ravenous and overwhelmed by the resurgence of food noise.”

OK, so this isn’t the fault of the drug. The single biggest variable in therapy is patient compliance. Stop taking the drug, stop doing the PT exercises, fall off the wagon, and you lose the benefits. 

I understand and share the impulse to minimize my intake of pharmacy. But largely owing to the fact that I won the genetics lottery, I don’t have the sorts of conditions that require chronic drug use*. And if the drugs have side effects, there’s a trade-off. 

But with GLP-1-based pharmacologies, the side effects of use are minimal. The side effects of stopping are significant. Stick with the program, peeps.

*I recently started eye drops for glaucoma, which I need to take once a day for the rest of my life if I don’t want to go blind from excess intraocular pressure. I’m happy to accept this minor inconvenience for the profound benefit.

https://www.medpagetoday.com/opinion/second-opinions/114009?xid=nl_secondopinion_2025-12-28&mh=eb71348a5ff6ae370cc6759bc5dc3300&zdee=gAAAAABm4u1YoCP4y5SBTJUyUyqo9KxZhft26L1xeGdP0BzzQQN1Pb_ifR6vFqhFh-3U6Q_nU7DbA-EawzzXKxSRhMOwjrOGuOKbf7OE641eN0HfnK6eObE%3D&utm_source=Sailthru&utm_medium=email&utm_campaign=WeekendOpinions_122825&utm_term=NL_Gen_Int_SecondOpinion_Active

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