It was nearly a decade ago now that I was first introduced to how a drug derived from the venom of a Gila monster would change my practice. The context was diabetes, and the rotation was one of my final electives as an MS4 at Grady Memorial Hospital in Atlanta, Georgia. My preceptor, an eminent diabetologist, waxed poetic on the mysterious molecule altering the standard of diabetic care. On a whiteboard, he demonstrated how the GLP-1 class promised to break the longstanding paradigm of insulin as a first injectable option for patients. The claim was stunning, but prescient: these drugs, then in their nascent forms, would one day become the face of diabetes care, promising to help patients lose weight while also bringing their diabetes under control. In sharp contrast to insulin, he argued, which caused patients to gain weight, this class did the opposite, helping them shed pounds in a virtuous cycle that seemed almost too good to be true.
Much has changed in the past 10 years, though much has not. Then, as now, the drugs required jumping through insurance hoops and remained out of reach for many financially. Much of our education was spent on reframing the conversation of uncontrolled diabetes as not a moral failing of our patients, but a chronic disease that could be managed. With the recent reclassification of obesity as a chronic disease, I feel thrust back into the early days of GLP-1s for diabetes, both in how I frame the initiation of the prescription and long-term prospects for therapy, and how I find myself talking about the possibility of something that once seemed completely out of the question: counseling a patient about taking a drug long-term to control their obesity.
Therein lies the rub: What do we mean when we say “controlling obesity”? In diabetes, the question is fairly straightforward: we’re looking for an A1c reduction, which we know is associated with a reduction in the downstream complications that seem to be related to uncontrolled sugars. In obesity, as anyone who has prescribed these medications knows, the answer is not quite so simple. Some patients with a normal or near-normal BMI ask for the drug for cosmetic reasons. Others who have much weight to lose, possibly much more than is feasible with the drug, want to be on it nonetheless. Still more are in search of a temporary solution: to lose weight for the summer, for a wedding, or simply to look good for their high school reunion. And of course, there are those for whom non-obesity indications — cardiovascular risk reduction, obstructive sleep apnea, and nonalcoholic fatty liver disease, as well as yes, diabetes — drive the prescription. The patient could in many ways not be less “one-size-fits-all” when it comes to treating them for this indication.
Looking at the data does not provide much in terms of solace for those looking to GLP-1s as a short-term treatment with longstanding benefits. Many patients, both by meta-analysis and anecdote, seem to gain a substantial amount of weight back after stopping these drugs. Whether patients are looking for a long-term solution or a quick fix, I find that counseling properly from the first becomes paramount. The magic injection (or in many cases now, pill) might be pitched as more amlodipine or atorvastatin than azithromycin — you’re going to be on it a while, whether or not you make the lifestyle changes that are recommended with the labeling. If you’d like to get off it and sustain success, it’s certainly possible — but you might be just as well off continuing it.
Where does this leave me, the PCP now 10 years removed from my first introduction to this “miracle drug”? My counseling has shifted to try to set appropriate expectations with my patients at the outset. I start by emphasizing that the drug works, and people lose weight on it. I then level set with them; sustainable weight loss is slow, perhaps 1-2 pounds a week, and my patients who have the most success in coming off the medicine work with a nutritionist and change their lifestyle as they go along. I outline that many of the side effects — the nausea, bloating, even gallbladder and pancreatitis-type issues — can be ameliorated at least somewhat by proactively cutting down on portion size and avoiding foods that exacerbate symptoms. Of course, I also let them know that side effects are still possible even if they follow the perfect diet and exercise program to a tee. I explain that cost is a barrier, and that insurance can be fickle when it comes to coverage; if there’s an interruption in therapy, they might rebound in terms of weight gain and they should buckle up for some ups and downs that may include denials, appeals, prior authorizations, and drug shortages. Finally, I assure my patients that no matter what happens in their weight loss journey, I will be with them along the way — if a side effect is bothersome, progress is stalling, or we want to stop together, I offer them my time and assistance in coming up with an alternative that works for them.
With this spiel down, the once-miraculous drug has become almost mundane in my day-to-day. Insurance issues aside, prescribing and counseling feel as natural for obesity as it does for hypertension. In 10 years, it wouldn’t surprise me if the modern-day weight loss blockbusters appear as old school to me as the first generation GLP-1s seem now, and if MS4s confidently walk into residency and beyond seeing today’s medicines as just another tool to achieve the goal of addressing a chronic illness. What I am relatively certain of is that in 10 years, whatever new, once-yearly pill or injection exists will still need a prior authoritzation.
