Topiramate, phentermine for children with obesity hold up in the real world

Treatment with phentermine, topiramate, or their combination appears to help children with severe, complicated obesity shed weight, according to real-world data.

In a cohort of 126 children (mean age 15.5 years, 61 percent girls, mean body mass index [BMI] 39.4 kg/m²) prescribed phentermine and/or topiramate, BMI decreased significantly through 12 months, reported lead researcher Dr Olivia Puccio, from Children's Hospital Colorado, Denver, Colorado, US.

The percent BMI change from baseline was –3 percent at 3 months, –4.7 percent at 6 months, –5.2 percent at 9 months, and –7.5 percent at 12 months. [Puccio O, et al, Pediatric Academic Societies Annual Meeting 2023]

“The variability in percent BMI reduction was best explained by time, number of comorbidities, and a time–age interaction (favouring ages 7–11 and 18–23 years over 12–17 years),” Puccio noted.

Significant changes in bicarbonate (mean difference, –2 to –3 mmol/L; p<0.001), creatinine (mean difference, 0.07–0.1 mg/dL; p<0.001), and heart rate (mean difference, 9 beats/minute at 9 months; p=0.013) were observed over time.

While statistically significant, the changes in bicarbonate and creatinine were not clinically concerning, according to Puccio. “[Meanwhile], heart rate changes on phentermine should be monitored on a case-by-case basis.”

As for safety, the most common side effects among those who discontinued treatment were mood change (8 percent) and gastrointestinal events (7 percent).

Of the children included in the analysis, 82.5 percent had severe obesity, 51 percent had at least three obesity comorbidities (mean 2.4), and 23 percent had an aetiologic factor beyond lifestyle alone (eg, hypothalamic obesity, intellectual disability).

More than half of the children received combination treatment with phentermine and topiramate, with the median time to first prescription being 308 days. A total of 71 children discontinued treatment, with the mean time to discontinuation being 164 days and the most common reason being loss to follow up (54 percent).

Useful weight-loss drugs

Phentermine is a sympathomimetic agent that centrally stimulates norepinephrine release and, to a lesser extent, serotonin and dopamine reuptake. These processes work to suppress appetite, as Puccio explained.

On the other hand, topiramate is thought to act centrally through the brain’s inhibitory neurotransmitter gamma-aminobutyric acid (GABA), suppressing appetite and increasing fullness, she added.

The combination of phentermine plus topiramate was approved by the FDA for chronic weight management in 12- to 17-year-olds in June 2022.

Despite the current study’s retrospective design and high rate of children lost to follow-up, the results affirm the use of phentermine and/or topiramate for paediatric patients with obesity in real-world clinical practice, according to Puccio.

As part of the bigger picture, the present data hold important clinical implications in light of the 2023 American Academy of Pediatrics guideline emphasizing that obesity is a chronic disease that warrants immediate treatment. What’s more is that many children with obesity are “unable to lose weight and achieve optimal comorbidity risk reduction with lifestyle changes alone,” Puccio pointed out.

The next steps in the research is to explore factors that contribute to patient attrition in the setting of antiobesity medication, assess the usefulness of standardized clinical protocols, and determine how lessons learned with antiobesity medications from a paediatric weight management program can be applied to other settings including primary care, she said.