Changing Mindset Is Crucial for Clinicians to Effectively Implement New Weight Management Medications

Clinicians must all work to change their mindsets around obesity, recognizing it as a chronic, relapsing, multi-factorial, neurobehavioral disease, according to Jennifer Clements, PharmD, FCCP, FADCES, BCPS, CDCES, BCACP, BC-ADM, clinical professor and director of pharmacy education at the University of South Carolina College of Pharmacy. Clements presented on the topic of weight management medications at the American Pharmacists Association (APhA) 2024 Annual Meeting and Exposition in Orlando, Florida.

“[Obesity] does go beyond just having that excess adipose tissue around the waist, although we know that that excess adipose tissue can lead to health consequences,” Clements said during the session.

Image credit: Wild Awake | stock.adobe.com

By 2030, there is a predicted prevalence of 50% of Americans with obesity, as well as 25% with severe obesity. Of those, 27.6% are women, 31.8% are non-Hispanic Black adults, and 31.7% are low-income adults, highlighting the populations most at risk.

When treating obesity, Clements said the general goals are to reduce morbidity, control concomitant risk factors, reduce complications, reduce body weight by 5% to 10%, and maintain lower body weight. However, she added that what comes after the weight loss can often be the most challenging.

“I think what’s even harder is preventing that weight from coming back; it’s the maintenance,” Clements said. “It’s really also going to be about talking about things to prevent that weight from creeping back up so that [the patients] can maintain it long-term.”

Lifestyle modifications, anti-obesity medications, medical devices, and bariatric surgery are the mainstays of this treatment, Clements said. When considering any of these options, Clements emphasized that the most important thing is to maintain a patient-centered approach, considering their unique needs in order to decide the best option for them. In particular, anti-obesity medications have developed rapidly in recent years, raising many questions about optimal use.

Clements reviewed 7 anti-obesity medications: phentermine, orlistat, phentermine in combination with topiramate, bupropion in combination with naltrexone, liraglutide, semaglutide, and tirzepatide. Notably, she pointed out that these all have the same indication as adjunct therapy with lifestyle modifications in individuals with a body mass index (BMI) of 27 kg/m² or greater and a weight-related comorbidity, or a BMI of 30 kg/m² or greater. With the exception of phentermine, which is indicated for 12-week use, all of these medications are long-term.

In addition to improved efficacy, newer generations of anti-obesity medications have significantly improved safety concerns, particularly with cardiovascular adverse effects (AEs). Clements did note, however, that any medication combining 2 drugs can be expected to have more drug–drug interactions and potential AEs, so patients receiving these medications should be monitored with that in mind.

Assessing patients for tolerability and dose titration is crucial because all of these medications can have significant AEs, particularly gastrointestinal. Clements said pharmacists should counsel patients that nausea can be expected during periods of dose titration, although it should subside with time.

Clinicians should also consider ease of use as well, according to Clements. Although the newest medications (eg, semaglutide, liraglutide, and tirzepatide) have once-daily or once-weekly dosing, others—notably phentermine plus topiramate—can have incredibly complicated dosing regimens.

Clements specifically reviewed data for 2 of the newest and most efficacious medications: semaglutide (Wegovy; Novo Nordisk) and tirzepatide (Zepbound; Lilly).

In the series of STEP trials examining semaglutide, Clements said one key finding was that patients who discontinued the drug did re-gain some weight. This was particularly observed among patients who established a maintenance dose of semaglutide by week 20 before switching to placebo, highlighting the remaining questions surrounding discontinuation.

Findings from the STEP-HFpEF trial effectively showed that quality of life improved with the use of semaglutide. Although Clements said this is an unsurprising finding—as patients lose weight and their health improves, naturally their quality of life should follow—she predicts more future studies like this one to show the benefits of these drugs in issues outside of hypertension and diabetes. Using data like these, companies can seek new FDA indications and push payers to cover these medications.

For instance, Clements said she predicts that Eli Lilly will pursue an indication in obstructive sleep apnea for tirzepatide by the end of 2024. This would be based on study data expected at a sleep conference later in the year.

Perhaps most notably, on March 8, semaglutide received a new FDA indication for cardiovascular risk reduction, based on findings from the SELECT trial. In this trial, participants with pre-existing cardiovascular disease and a BMI of 27 kg/m2or greater without diabetes were randomized to semaglutide 2.4 mg or placebo for an average of 34.2 months. In the primary outcome of 3-point major adverse cardiovascular events, risk was reduced by 20% in the semaglutide arm compared with the placebo arm. Furthermore, over 5 years, the reduction in risk was seen regardless of baseline age, sex, race, ethnicity, BMI, and level of renal function impairment.

Tirzepatide has also garnered a lot of public attention, Clements said, following its FDA approval based on findings in the SURMOUNT-1 and -2 trials. The SURMOUNT-3 trial examined intensive lifestyle interventions for 12 weeks before patients received tirzepatide. Interestingly, patients lost around 6% of their body weight during the lifestyle interventions, followed by an additional 18.4% while on tirzepatide. Clements said this highlights the importance of lifestyle interventions, both with and without anti-obesity medications.

One notable gap in research is head-to-head trials comparing various anti-obesity medications. However, there are some data comparing semaglutide and tirzepatide, which has found similar efficacy, low risks of hypoglycemia when used as monotherapy, and similar time to maximum dose. Importantly, semaglutide has the FDA-approved indication for reduced cardiovascular risk.

Of course, key challenges with all of the new anti-obesity medications include availability and cost, both of which pharmacists can help patients navigate. When grappling with limited availability, Clements said pharmacists can take several steps: contact an authorized supplier, review information from the manufacturer, contact other pharmacies or clinics, suggest alternative treatments, and emphasize the value of non-pharmacological therapy.

Due to shortages, Clements acknowledged that compounded anti-obesity medications have been a major topic of discussion in recent weeks. Although she said these options can be safe and efficacious when done properly by a licensed, regulated compounding facility, Clements emphasized the need for caution.

Additionally, like AE tolerance and clinical recommendations, Clements said managing costs can depend on individual patients and their needs.

“Obviously there are strategies. Let’s say some can’t afford it; you may have to go to a generic option or emphasize lifestyle modifications,” Clements said in an interview with Pharmacy Times. “I think it’s just really dependent on that person and how much they can budget out for their medications as a whole with everything else they have to pay for. But you can always think outside the box for those scenarios.”

Moving forward, Clements said she believes anti-obesity medications will continue to become more effective, even reaching the point of efficacy similar to bariatric surgery. Pharmacists can continue playing a large role in these treatments through educating providers, counseling patients, and publishing research.

“People have got to be doing things, and I think this would be a good time for them to look at what they’re doing and consider some type of publication to get the word out there, so that we can all learn from each other,” Clements told Pharmacy Times.

REFERENCE

Clements J. Weight Management: Rise of the Resistance. Presented at APhA 2024 Meeting and Exposition. March 22, 2024.