The escalating demand for obesity medications including semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) over the past six months, amplified by digital- and tele-health companies chasing the “obesity gold rush,” highlights a crucial point in our battle against obesity.
Given the rapid rise of obesity over the last 2 decades, the failure of our diet culture, and the lack of non-surgical solutions, it’s easy to celebrate the impressive results yielded by clinical trials of semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro). However, the current prescribing patterns and ensuring medication shortages, raises questions on if real-world utilization is consistent with the clinical trial guidelines.
Let’s pause for a moment and examine the clinical environment in which these drugs were developed. What we will find is that real-world practice is a reality far removed from controlled trial settings and this gap is being overlooked in the adoption of obesity medications.
Keeping Up With Follow-Ups
When we dig into these trials, a striking fact stands out: the sheer number of follow-ups. The tirzepatide study, for instance, had an astonishing 46 touchpoints in 3.5 years. The Wegovy trial provided 34 phone visits and 17 lifestyle counseling sessions over 68 weeks. Such high levels of engagement are difficult to replicate in real-world practice and can lead to considerable differences in outcomes.
Moreover, despite this intensive follow-up, 17-19% of people did not adhere to semaglutide and tirzepatide in the clinical trial, with only 40-50% of poor adherence due to medication intolerance. Could we expect better adherence in a less supervised setting? Highly unlikely.
Studies in people with diabetes demonstrate that real-world outcomes of GLP-1s are 50% less than what has been observed in the clinical trials. The gap between expected and real-world outcomes was attributed to poor medication adherence and a more diverse treatment population, a trend we should expect to see magnified with obesity medications.
Additionally, anywhere from 10-25% of patients do not achieve more than 10% weight loss on semaglutide nor tirzepatide. While 10% weight loss is a great clinical achievement, any practicing obesity physician can tell you that the average patient wants to lose more. Without proper education and counseling, many of those patients will have a hard time sticking to a therapy with less than desired outcomes.
The Overlooked Role of Lifestyle Modification
Another critical aspect often overlooked in these trials is the extent of dietary and lifestyle counseling provided to the participants, performed by a dietitian or an equivalent healthcare professional. The frequency of counseling varied between the two studies — 9 sessions in 72 weeks for the tirzepatide trial and 17 sessions in 68 weeks for the semaglutide trial. In addition to counseling sessions, participants were required to track their food and activity. Our overburdened healthcare system struggles to offer this level of attention, yet its importance cannot be overstated. We need to invest in ancillary or multispecialty staff who can provide this critical support.
Exclusion Criteria: Are We Ignoring the Details?
Then, there’s the complexity of exclusions. How often are we aware of or educate patients on these factors that can significantly alter medication responses? Individuals with recent psychiatric disorders, severe depression, malignancy, or recent cardiovascular events, those taking weight gaining drugs or contraceptives, and even those who recently tried a fad diet, were excluded from these trials. In reality, these individuals constitute a large portion of our patient pool. For example, both trials excluded people who had lost or gained 11 lbs in the last 90 days. In the real world, that might be more than 50% of people seeking medication today. Are we considering these factors in our daily practice when prescribing these medications? Do we wean people off weight gaining medications? Do we adjust the plan for people with severe depression? The reality is that we are often not factoring in exclusion criteria in our decision making and ramifications on outcomes are unclear.
Physiological Considerations and Medication Adjustments
Almost 40% of weight loss was lean body mass in the Wegovy trial, which is a significant consideration for patients with sarcopenic obesity or low muscle mass, as further skeletal muscle loss could have long-term detrimental effects. Additionally, 34% stopped or decreased their blood pressure medication, requiring careful monitoring of blood pressure during therapy to avoid syncope or hospitalization. Furthermore, the long-term implications of 19% of individuals ceasing or reducing their statin medication on cardiovascular mortality still remain uncertain. Are physicians monitoring for ramifications and sequelae of weight loss? Do they have the programs and ancillary resources available to adjust the plan for people with sarcopenia, or remote monitoring in place to help adjust blood pressure medications?
So, what does all this mean for us, the healthcare providers on the frontline? It means a reality check. These medications were developed in a care environment with significant and rigorous follow-up, monitoring, counseling, and tracking. It’s important to note that in these settings, the placebo group achieved a sustained 3% weight loss.
It’s crucial that we contrast this with our current panel management scenarios where, regrettably, our panels are on average gaining 1-2% of their weight over a similar period of time. Therefore, achieving sustained 3% weight loss as a standard of care currently seems a far cry from reality.
However, we should not view this as an insurmountable challenge, but rather as a call to action. As we prescribe these medications, we should also be investing in a holistic care team with comprehensive programming, remote monitoring, and proactive patient engagement pathways. We need to strive not just to replicate but to surpass the care standards set by these clinical trials. The current obesity epidemic demands a transformative approach to healthcare, where medication is just one component of a more comprehensive solution.