Jonathan (Yoni) Freedhoff, MD

DISCLOSURES | January 31, 2025

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Seemingly, not a day goes by where the benefits of our new generation of obesity medications aren’t enthusiastically touted — be it the weight loss they provide, or the ever-growing myriad of other diseases they are shown to prevent or improve. They are now regularly described as the most important new class of medication in decades. Given all that, why is it that in this study, for instance, by 12 months, 60% of those prescribed semaglutide (Ozempic/Wegovy) were nonadherent to taking it? This month, a new review article set out to explore the different factors playing into this phenomenon. 

The authors divide nonadherence into three different categories: those of initiation, implementation, and persistence. Broadly, initiation nonadherence would be not filling prescriptions, implementation nonadherence would be not taking the medication for long enough to reach a therapeutic dose, and persistence nonadherence would be stopping the medication despite the condition chronicity. Let’s review some of the common factors involved in these three types of nonadherence, and some thoughts from the authors and from my experience, as to how to avoid them. 

Initiation Nonadherence

Initiation nonadherence, the authors say, may start with the skill and empathy of the healthcare prescriber. How you counsel your patients with respect to the risks and benefits of these medications matters in terms of whether they feel comfortable filling their prescriptions. 

In my experience, it helps a great deal to remind patients that when it comes to medications, if they don’t work we stop them, and if they lead to side effects that don’t disappear — we stop them. 

It also helps to explain that within 3 months, patients will know with certainty whether these medications provide them with sufficiently worthwhile benefits to continue with them. The initial prescription in a sense is a 3-month experiment that will provide them with a personal frame of reference upon which they, not their prescriber, will decide their worth. 

Explaining the many benefits of these medications beyond their impact on weight can also help assuage the implicit weight bias and guilt that lead many patients to be reluctant to consider these medications. These medications are used to both treat obesity and to mitigate risk, and their prescription does not preclude concomitant lifestyle change. Especially for patients who are taking medications to manage weight-responsive comorbidities, you might consider describing these medications as being medications for those comorbidities — for instance, that patient with hypertension may discover that with weight loss, they no longer need their other antihypertensives. 

The prescriber’s attitude also matters because if the prescriber, rather than presenting these medications free from blame or shame, discusses them as a last resort, or an easy way out, or as a surrender, this may lead patients to feel guilty about their use and to not accept or fill their initial prescription. 

It probably goes without saying that another common reason for initiation nonadherence is cost and coverage. Given that medications prescribed for a chronic condition require long-term use, if a patient is not covered or cannot afford these medications, it should not be surprising if they never start them.

Implementation Nonadherence

Implementation nonadherence may be in part due to the long titration period. If your patient isn’t counseled about the possibility that at the lowest doses, they might not experience a dramatic impact on their hunger, cravings, or fullness, they may decide in the early days that these drugs are not effective and discontinue them before reaching therapeutic doses.

Another primary player in implementation nonadherence is continued dose titration in the face of side effects. Generally, side effects tend to dissipate with ongoing use; however, some patients are more sensitive to these medications than others and take longer to experience dissolution of any adverse effects. In those patients, increasing the dosage slowly, and potentially even by amounts not mentioned in the monograph or indicated on their quick pens (ie, advancing by a smaller number of clicks on their medication pens), can at times see patients reach therapeutic dosages who otherwise would have discontinued due to side effects. 

Ensuring regular communication and visits prior to each dose increase will allow the clinician to evaluate whether to continue a patient on a lower dose until side effects diminish, or to increase the dosage by a lesser amount than is normally tolerated.

Persistence Nonadherence

Finally, there’s persistence nonadherence, which is a mixture of all the above. For some, it will be due to ongoing costs. For others, it may be due to ongoing side effects — and here clinicians can help by simply treating them. 

But I would wager that for a large percentage of patients, it’s consequent to poor understanding or counseling around the fact we are treating a chronic condition, not curing an acute one, and/or a poor understanding of realistic outcomes. Obesity medications aren’t antibiotics for weight, yet many patients believe that stopping them following weight loss won’t necessarily lead to weight regain and stop them once they’ve stopped losing weight. 

For most, cessation will lead to significant regain over time and it is incumbent upon clinicians not just to ensure that this is clear at a prescription’s outset, but also to contextualize in terms of how we treat all other chronic diseases. 

Although internalized weight bias undoubtedly challenges patients’ comfort with long-term use of these medications, patients will readily understand that we don’t stop antihypertensives when blood pressure normalizes. Explicitly discussing and reinforcing this is likely to help with your patients’ persistence on these medications. Similarly, patients need to understand the average expected weight loss consequent to the medication you prescribe before you prescribe it. Not meeting unrealistic expectations may well lead people with suboptimal weight loss to discontinue a medication that has conferred very meaningful clinical benefits. 

As comfort and experience with these medications grow both among clinicians and among the public, adherence will probably improve. Until then, there is much a clinician can do to help ensure that if their patients are nonadherent, it’s not for reasons that thoughtful counseling and follow up would have prevented. 

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