Overview of the Medications
There are currently six obesity medications approved by the Food and Drug Administration (FDA) for use in youth: Phentermine, orlistat, liraglutide, phentermine/topiramate, semaglutide, and setmelanotide.
Of these, orlistat is rarely used now because it results in the least amount of change in BMI (about a 3% loss change in BMI), has a lot of gastrointestinal side effects, often is not covered by insurance, and is expensive out of pocket. Setmelanotide is indicated only in those aged 6 years or older who have obesity because of Bardet-Biedl syndrome or one of three other rare genetic conditions: a POMC, LEPR, or PCSK1 deficiency. Fox therefore focused on the other medications besides these two.
While nearly all the currently available obesity medications are only approved in those aged 12 years or older, Fox noted that studies are ongoing at younger ages, so some of these medications may receive approval in younger populations in the future. The only one currently available for a younger age is liraglutide, which is approved down to 6 years old in children with type 2 diabetes.
“Very young kids who have very severe forms of obesity need intervention, and unfortunately, at this point, we really don’t have much to offer them,” Fox said.
Fox highlighted six key factors to consider in selecting a medication for those aged 12 years or older, though one of these, in the US healthcare system, can tend to trump all the others. Those factors are mechanism of action, side effect profile, effects on other diagnoses, patient/family preferences, provider comfort, and finally — the potentially overruling one — insurance coverage and access.
“These days, insurance coverage and access are really the No. 1 driver when I’m seeing a patient,” Fox said. “The first thing I do is look at their insurance and then also look at what kind of updates our pharmacist has given us about which medication is currently in stock.”
Each medication has different properties that should be considered with the child’s health profile. For example, topiramate is a carbonic anhydrase inhibitor so likely shouldn’t be prescribed in a child who is taking any other carbonic anhydrase inhibitor. Fox said she probably wouldn’t prescribe phentermine in a child with severe anxiety because it might enhance the anxiety effect. But if a child has migraines, she may be more inclined to try phentermine/topiramate first because the topiramate may help with the migraines. Similarly, if a child has type 2 diabetes or prediabetes, she may lean toward one of the glucagon-like peptide 1 (GLP-1) agonist drugs.
Liraglutide and Semaglutide
Liraglutide and semaglutide are both GLP-1 receptor agonists administered subcutaneously to reduce appetite, increase satiety, slow gastric emptying, and reduce the food reward response in the brain. Liraglutide can result in up to 4.5%-5% change in BMI, and semaglutide, the most potent of all the medications, can result in up to a 17% change in BMI.
Liraglutide and semaglutide are both approved for patients aged 12 years or older who weigh at least 60 kg and have a BMI of at least the 95th percentile. Liraglutide is also approved for those aged 10 years or older with type 2 diabetes. Both are contraindicated in those with a family history of medullary thyroid cancer or multiple endocrine neoplasia II. The risks to watch for include pancreatitis and gallbladder disease. Also keep in mind if you have a patient with type 1 diabetes and insulin resistance; prescribing a GLP-1 agonist is appropriate, but their insulin needs will decrease, necessitating close monitoring of their blood glucose, Fox noted.
These GLP-1 medications can be considered for those who have insurance coverage for them, who have diabetes or prediabetes, who are comfortable with daily (liraglutide) or weekly (semaglutide) injections, who have food cravings, and who have poor satiety or satiation. Without insurance, these medications are very expensive.
The most common side effects include injection site reactions and nausea, vomiting, and diarrhea, though all these usually fade and can be minimized with small portions and slower eating if needed. Less common possible side effects can include abdominal pain, constipation, headache, dizziness, fatigue, and hypoglycemia. If patients develop severe belly pain that radiates to their back, they should be assessed for pancreatitis.
It’s also important to demonstrate for patients how to do the injections, Fox said. Liraglutide dosing begins at 0.6 mg daily for a week, followed by a week at 1.2 mg, a week at 1.8 mg, a week at 2.4 mg, and then 3 mg daily. Semaglutide dosing starts at 0.25 mg weekly for 4 weeks, then going up each subsequent month as needed to 0.5 mg, then 1 mg, then 1.7 mg, and finally 2.4 mg. Though there’s no standard follow-up schedule for these medications, Fox suggested considering monthly visits for the first 3 months and then every 2-3 months to assess heart rate and blood pressure, the injection site, adherence, side effects, and the effect on BMI and eating.
“Are they getting appetite suppression, but not too much appetite suppression?” Fox said. “Just like in eating disorder treatment, we want our patients to eat regularly spaced meals. If their appetite is so suppressed that they are hardly eating anything, that’s a problem.”
Fox also offered the following additional pearls about these medications:
- Though manufacturers have struggled to keep up with demand, the shortages of these medications are improving. However, beware the compounding pharmacies filling the gap because compounded medications are not FDA approved, and quality control issues are a concern.
- Prior authorizations are usually needed, and common reasons for denial to anticipate include lack of documentation on not having contraindications, the patient not following a low-calorie diet or engaging in physical activity, and the patient not having seen a registered dietitian.
- Patients should expect gastrointestinal side effects, but ondansetron can be prescribed to lessen the intensity.
Phentermine/Topiramate
Phentermine/topiramate extended-release is a once-daily oral tablet, with the phentermine acting to reduce appetite (by simulating the release of norepinephrine) and the topiramate reducing caloric intake and food reward response (by increasing gamma-aminobutyric acid activity). It’s approved for those aged 12 years or older with a BMI of at least the 95th percentile and should be considered in those with strong hunger, low energy, binge eating disorder, or migraines, as well as those who have insurance coverage for it. It can result in up to a 10% change in BMI.
Contraindications include pregnancy, substance use, cardiovascular disease (though it’s okay in patients with controlled hypertension), hyperthyroidism, glaucoma, and monoamine oxidase inhibitor (MAOI) use. Fox emphasized the teratogenic effects, so patients capable of pregnancy need to be on reliable birth control. The most common side effects include paresthesia, dizziness, dysgeusia, insomnia, and constipation.
A risk of topiramate is kidney stones, so patients should drink a lot of water, especially in hot weather, Fox said. Other risks can include metabolic acidosis, suicidality, poor cognitive function, high blood pressure, and renal impairment.
“If your patient is struggling academically, I might use this medication a bit more cautiously, particularly when the dose gets above 100 mg a day,” Fox said. “That’s when the cognitive effects tend to emerge more strongly.”
Patients with congenital heart disease should meet with their cardiologist before starting this medication, and although patients taking selective serotonin reuptake inhibitors (SSRIs) can take this, there is a potential increased risk for serotonin syndrome because phentermine has a little bit of serotonergic activity, she said.
Before prescribing, do an exam to ensure the patient doesn’t have a heart murmur, isn’t hypertensive, isn’t pregnant, has normal kidney function, and has bicarbonate in a reasonable range. Dosing begins with a daily 3.75/23-mg capsule for 2 weeks, followed by 2 weeks at 7.5 mg/46 mg. As with the GLP-1 drugs, Fox advises considering monthly follow-ups for the first 3 months and then visits every 2-3 months. Each visit should include the assessment of cardiovascular health, heart rate, blood pressure, side effects, pregnancy risk, and the medication’s effect on BMI and eating. If the patient is tolerating a dose of 7.5 mg/46 mg, it can be increased to 11.25 mg/69 mg for 2 weeks and then to 15 mg/92 mg. Bicarbonate and creatinine should be checked every 6-12 months; if bicarbonate < 18 mEq/L, the dose should be reduced and then bicarbonate should be checked again a month later.
Fox noted that this drug is expected to go off patent in late 2024 or in 2025, which will substantially reduce the cost. It’s also possible to prescribe phentermine and topiramate separately, which may reduce costs or help with insurance coverage and can allow for evening dosing of topiramate.