DENVER — The ability to provide adolescents with highly effective anti-obesity medications that now carry approvals from the US Food and Drug Administration (FDA) and support in guidelines offers reassurance of their use; however, a reality check often awaits for clinicians in terms of challenges ranging from accessing and affording the medications to managing real and rumored side effects.
Weighing in on the issues, experts at Obesity Medicine (OMA) 2024 offered some key strategies and practice hacks for overcoming those hurdles.
The incentive to provide treatment with popular glucagon-like peptide 1 (GLP-1) drugs such as semaglutide or the dual glucose-dependent insulinotropic peptide (GIP) GLP-1 tirzepatide lies in the evidence that their high efficacy in promoting weight loss, and hence preventing metabolic syndrome, has benefits that far outweigh the potential side effects, said Alaina Vidmar, MD, in presenting at the meeting.
“We can look at all the evidence and without question acknowledge that the GLP-1s/GIP agonists are the most effective agents that we currently have, with the least heterogeneity in response, and the most high responders compared with other agents,” said Vidmar, an assistant professor of clinical pediatrics at the Keck School of Medicine of University of Southern California and director of obesity medicine and bariatric surgery at Children’s Hospital Los Angeles, Los Angeles.
The strength of the evidence is reflected in the landmark American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity, which recommends that “pediatricians and other primary healthcare providers should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks and may offer adolescents 8 years old with obesity weight loss pharmacotherapy, according to medication indications, risks.”
The AAP guidance echoes the recommendations of the drug makers and FDA that “a combination of specific behavioral techniques within the context of family-based behavioral treatment and the use of pharmacotherapy may be necessary to prevent life-limiting complications over time.”
However, in real-world practice, with the various challenges in providing that intensive, comprehensive care, clinicians should be prepared to get creative: “We sometimes have to do the best we can with what we have because the watchful waiting approach is not effective and leads to more harm than good,” Vidmar said.
Facilitating Access
The ongoing reported shortages in the highly popular anti-obesity medications, as well as insurance denials and high costs, are among the leading obstacles, for adolescents and adults alike.
Vidmar noted that key strategies at her center, Children’s Hospital Los Angeles, have been essential, however, in helping at least facilitate the authorization process.
The center’s approach began with contacting all the payers the center has contracts with to determine which of their policies cover these medications for adults and pediatrics and which agents are covered.
“This took work on the front end, but it was worth it because it helped us understand the framework for what we were going to go up against every time that we prescribed these medications,” she said.
Furthermore, the center’s specialty pharmacy set up contracts to be able to provide the drugs within the institution.
While the strategy can’t entirely mitigate the ongoing distribution concerns, “our pharmacy is now able to share with our weight management program what GLP-1s are available so that we can be more efficient in our work,” Vidmar said.
The center also created a list of contacts to provide to patients and their families, detailing local pharmacies that were most likely to have the medications.
Another strategy Vidmar’s center has utilized to allow the timely implementation of a GLP-1 treatment plan while awaiting a drug to become available is to create an alternative protocol, for instance, using liraglutide when awaiting semaglutide.
“If we are unable to get the lower doses of a weekly agent for titration, we have a standard protocol to bridge instead with liraglutide, and our patients, pharmacies, and even our authorizations are aware of the protocol,” Vidmar said.
“We often do not have a lot of control or agency over the distribution concerns; however, we can be thoughtful within our programs about how we titrate patients up to their full doses,” Vidmar said.
Mitigating Side Effects
When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Vidmar noted.
“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.
Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”
Vidmar shared a handout of her center issues with key recommendations for mitigating GI effects in youth. These include:
- Eat smaller meals and eat slower
- Eat about half of what you usually eat
- Take about 15-20 minutes to eat your meal
- Aim for 60 g of protein per day
- Add fruits, vegetables, whole grains, and lean proteins to meals
- Limit foods that are spicy, greasy, or fried
- Drink water instead of sweet drinks
- Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Vidmar said.
Regarding the GI effects, Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
Mood Concerns?
Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.
Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”
Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
Concurrent Psychiatric Pharmacotherapy
Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.
Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.
In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.
The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”
Commenting to Medscape Medical News, first author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”
Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”
“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.
To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”
However, the newer anti-obesity medications could prove to be important in those cases, Vidmar added.
“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”
Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.