A shift in mindset is critical for clinicians to effectively introduce new weight management drugs

According to Dr. Jennifer Clements, Clinical Professor, FCCP, FADCES, BCPS, CDCES, BCACP, BC-ADM, clinicians all recognize obesity as a chronic, recurrent, multifactorial neurobehavioral disease. He says we need to be aware of this and work to change our attitudes towards obesity. Director of Pharmacy Education at the University of South Carolina School of Pharmacy. Mr. Clements spoke on the topic of weight management drugs at the American Pharmacists Association (APhA) 2024 Annual Meeting and Exposition in Orlando, Florida.

“[Obesity] We know that excess adipose tissue can lead to health problems, but it's more than just having excess adipose tissue around the waist,” Clements said during the session.

By 2030, 50% of Americans will be obese and 25% will be severely obese. Of these, 27.6% were women, 31.8% were non-Hispanic black adults, and 31.7% were low-income adults, highlighting the populations most at risk.

General goals in treating obesity are to reduce morbidity, control associated risk factors, reduce complications, reduce body weight by 5% to 10%, and maintain a low body weight, Clements said. Stated. But what happens after weight loss can often be the most difficult, she added.

“I think what's even more difficult is making sure you don't put the weight back on. It's maintenance,” Clements said. “We will also discuss things you can do to prevent the weight from gaining back on. [the patients] Can be maintained over the long term. ”

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

Clements reviewed seven antiobesity drugs: phentermine, orlistat, phentermine plus topiramate, bupropion plus naltrexone, liraglutide, semaglutide, and tirzepatide. Of note, she pointed out that these are all the same indications for adjunctive therapy with lifestyle modification for an individual with a body mass index (BMI) of her 27 kg/m3.² or above and have weight-related comorbidities or have a BMI of 30 kg/m or above² that's all. All of these drugs are long-term doses, except for phentermine, which requires 12 weeks of use.

In addition to improved efficacy, the new generation of anti-obesity drugs has also significantly improved safety concerns, particularly regarding cardiovascular adverse effects (AEs). However, Professor Clements said that patients receiving these drugs should keep this in mind as combinations of two drugs can be expected to increase the likelihood of drug-drug interactions and adverse events. He pointed out the need for monitoring.

All of these drugs can cause serious adverse events, especially gastrointestinal, so it is important to evaluate patients for tolerability and dose escalation. Clements said pharmacists should advise patients that nausea should subside over time, but nausea may occur during dose titration.

Clinicians also need to consider ease of use, according to Clements. Newer drugs (such as semaglutide, liraglutide, and tirzepatide) are given once a day or once a week, but dosing regimens for other drugs, especially phentermine and topiramate, can be quite complex.

Mr. Clements specifically reviewed data for two of the newest and most effective drugs: semaglutide (Wegovy, Novo Nordisk) and tirzepatide (Zepbound, Lilly).

In the STEP series of trials looking at semaglutide, one key finding was that patients who stopped the drug gained some weight, Clements said. This was particularly observed in patients who were placed on a maintenance dose of semaglutide by week 20 before switching to placebo, highlighting remaining questions surrounding discontinuation.

The results of the STEP-HFpEF trial effectively demonstrated that the use of semaglutide improved quality of life. Dr. Clements said this was not a surprising finding, but that if patients lost weight and their health improved, their quality of life would naturally follow, but problems other than high blood pressure and diabetes We anticipate that more such studies will be conducted in the future to demonstrate the benefits of these drugs in patients. Using such data, companies can push the FDA for new indications and encourage payers to cover these drugs.

For example, Clements said he expects Eli Lilly to pursue the obstructive sleep apnea indication for tirzepatide by the end of 2024. This will be based on research data expected at a sleep conference later this year.

Perhaps most notably, on March 8, semaglutide received a new FDA indication for cardiovascular risk reduction. SELECT trial. In this trial, participants with pre-existing cardiovascular disease and non-diabetic body mass index of 27 kg/m2 were randomly assigned to receive semaglutide 2.4 mg or placebo for an average of 34.2 months. For the primary endpoint of three major adverse cardiovascular events, the risk was reduced by 20% in the semaglutide group compared to the placebo group. Furthermore, over a 5-year period, the risk reduction was seen regardless of baseline age, sex, race/ethnicity, BMI, or level of renal impairment.

Tirzepatide has also received a lot of public attention following its FDA approval based on the results of the SURMOUNT-1 and -2 trials, Clements said. The SURMOUNT-3 trial investigated an intensive lifestyle intervention over 12 weeks before patients received tirzepatide. Interestingly, patients lost approximately 6% of their body weight during the lifestyle intervention, followed by a further 18.4% loss while receiving tirzepatide. Clements said this highlights the importance of lifestyle interventions, with or without anti-obesity drugs.

One notable gap in research is head-to-head trials comparing different anti-obesity drugs. However, there are some data comparing semaglutide and tirzepatide, finding similar efficacy, lower risk of hypoglycemia when used as monotherapy, and similar times to maximum dose. Importantly, semaglutide has an FDA-approved indication for cardiovascular risk reduction.

Of course, the main challenges for any new anti-obesity drug include availability and cost, and pharmacists can help patients address both of these. Clements said pharmacists can take several steps when addressing limited availability. These include contacting qualified suppliers, verifying information from the manufacturer, contacting other pharmacies and clinics, suggesting alternative treatments, and emphasizing the value of non-drug treatments.

Clements acknowledged that combination anti-obesity drugs have been a hot topic in recent weeks because of the shortage. Clements said these options can be safe and effective if properly implemented by a licensed and regulated compounding facility, but stressed the need for caution.

Additionally, controlling costs, as well as AE tolerance and clinical recommendations, may depend on the individual patient and their needs, Clements said.

“Obviously there's a strategy. Let's say some people can't afford it. They may need to go to popular options or focus on lifestyle modifications,” Clements said. Interview pharmacy times. “I think it's up to the person and how much they can budget for drugs overall, including all other costs. But you can always think outside the box when it comes to those scenarios. I can think about it.”

Clements said he believes anti-obesity drugs will become even more effective in the future, reaching the point where they can be as effective as bariatric surgery. Pharmacists can continue to play a major role in these treatments by educating health care providers, counseling patients, and publishing research.

“People have to do something, and I think now is a good time to look at some kind of publication to see what they are doing and get it out to the public. , we can all learn from each other,'' Clements said. pharmacy times.

reference

Clements J. Weight management: increasing resistance. Presented at the APhA 2024 Conference and Exhibition. March 22, 2024.