Lots of GLP-1RA skepticism comes from the ethereal assumption that these drugs were marketed as miracles, even though they are nowhere near that. New drugs that are markedly effective can seem miraculous, but they carry all the side-effects and symptoms of the medicines that preceded them.
GLP-1RAs have all the features of a drug. For those who need them, the potential and benefits are there; for those who don’t, the effects of abuse are visible, social and physical. We find side-effects in either case, and they have been communicated clearly.
First, GLP-1RAs have a categorical impact on your digestion. This stems both from the desired mechanism (changes to hunger increase nausea) and from the blast radius of the pharmacology (neurons in the area postrema carry GLP-1 receptors, and they generate nausea when fired).
These changes are not pleasant, and even if they start mild, they get worse as the dose increases. The stomach and the bowels are both impacted. Patients sometimes have disruption that reaches stomach paralysis, which requires hospitalization. The risk is known.
Tolerance builds and side-effects may decrease, but they nonetheless persist. I am on tirzepatide, and in the ten months I’ve taken it, the nausea has at no point subsided, only increased. It is tolerable, but only when I consider it a sacrifice for weight loss.
And then there are those who lost their vision to NAION (even if extremely rare and mostly confined to semaglutide, with reduced risk in newer GLP-1RAs), developed psychiatric issues, or developed malnutrition. These have not gone unacknowledged or ignored.
Most patients on GLP-1RAs feel the impact of the drug and do not live unscathed, with many discontinuing it because of the decrease in quality of life. However, most persist because the benefits exceed the risks, the biggest being relief from the mortality of obesity, which has been difficult to treat if you have the drug prescribed. And the decrease in quality of life is relatively trivial next to the great decreases that obesity creates overall, with any loss offset by the gains of a good night’s sleep and GERD disappearing.
GLP-1RAs are for those who cannot conventionally lose weight, and the unfortunate who remain obese despite countless attempts to diet and exercise are exactly those people. Possessing the will to do either but failing to execute means you cannot conventionally lose weight, and it is perhaps something in the brain that creates that inability. It could be comorbid with other illnesses, but it also exists on its own, which is most likely its main form. It could be that the contemporary overexposure to satiating food creates the condition and its permanence.
Treating obesity that persists despite the personal will to fight it goes beyond diet and exercise, even though the two are necessary and indispensable in therapy. Today’s drugs stand as new solutions with a smaller pharmacological blast radius than amphetamines or the naltrexone/bupropion combination pills that were standard before. But all of these carry side-effects, and the methodology of medical treatment alerts us to the downsides of any therapy involving medicine. That hasn’t been ignored or underdeveloped with GLP-1RAs, despite the widespread assumption that it was, because of the effectiveness and popularity of the drug class.
These are not prescribed in the manner of opiate pill-pushers. Many doctors here are skeptical of GLP-1RAs due to the chronic treatment involved, which resembles the lifelong regimens traditionally associated with more conventional diabetic therapies like metformin. This sad resistance comes from a category error, with doctors considering obesity an acute problem fixable through trivial adjustments to life, when it is in fact, for many, a chronic problem that cannot be resolved without the additional assistance of medical therapy, and that will return without both medical therapy and lifestyle adjustments. When the chronicity of obesity is understood, the skepticism disappears.