Pediatric Research Update | Pharmacologic Interventions for Pediatric Obesity

Each month, the OMA Pediatric Committee reviews a pediatric-focused obesity research update to help keep you up to date about the latest findings. This month’s update refers to a systematic review of pharmacological interventions in children and adolescents with obesity.

Article Summary

Overall, pharmacological intervention in children and adolescents with obesity was associated with greater reduction in BMI and improvement in quality of life compared with placebo or lifestyle modifications alone, driven mainly by Phentermine + Topiramate and Semaglutide.

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Article Review

Until recently, interventions for treatment of obesity in children and adolescents were focused primarily on lifestyle modifications alone. However with the advent pharmacological interventions that have been approved for adolescents, the landscape of obesity treatment has been changing rapidly. Based on prior reviews of lifestyle modification interventions, the decrease in body mass index (BMI) is typically small and not clinically significant. New anti-obesity medications however have been associated with significantly greater decreases in BMI and are featured as part of treatment guidelines by the Obesity Medicine Association and American Academy of Pediatrics. Prior meta-analyses examining the use of pharmacological interventions for obesity management in children and adolescents have not included the newest anti-obesity medications. This systematic review includes clinical trials published between January 2016 and March 2023. Further, various outcomes were analyzed including body mass index and health-related quality of life (HRQoL). Studies were also assessed for bias and strength of evidence was rated.

35 randomized control trials (RCTs) were included in the meta-analysis. Duration of intervention was between 12 weeks to 2 years. The medications used included Metformin, Fluoxetine, Sibutramine, Lorcaserin, Topiramate, Phentermine+Topiramate, Orlistat, Exenatide, Liraglutide, and Semaglutide; however the majority of the studies utilized Metformin monotherapy.. Overall, the two treatments that were associated with significant decrease in BMI were Phentermine + Topiramate and Semaglutide. Liraglutide also was associated with small decrease in BMI. The remainder of the agents had small effect sizes and did not have consistently significant decreases in BMI across studies. Overall there was no increased risk of serious adverse events (with a rate of 1 in 100 adolescents which did not differ between intervention and control groups) or trial discontinuation (except for Liraglutide) . Liraglutide and Semaglutide weight management doses were associated with risk of adverse effects requiring dose adjustment. Significant improvement in HRQoL was found with Semaglutide use.

The meta-analysis presented pooled data to show that overall pharmacological intervention results in significant improvement in BMI and HRQoL with moderate quality evidence. However, it appears that these improvements are driven largely by two medications: Semaglutide and Phentermine + Topiramate (though the authors caution drawing too many comparisons in effect size between the studies due to difference in sample size). Indeed, these medications have both been approved by the United States Food and Drug Association for treatment of obesity in children and adolescents ages 12 and older. Unfortunately not all insurance companies cover these medications and in many cases they are cost prohibitive. However, understanding the overall beneficial effects, and particularly when comparing with other pharmacological interventions, can aid clinicians and families in choosing whether or not to initiate anti-obesity medication in addition to lifestyle modifications.

Recently, the United States Preventive Services Task Force stated that there is “insufficient evidence” to recommend use of weight loss medication in children and adolescents. This heightens the need for further studies assessing the newer weight loss medications in children and adolescents. Given the evidence presented in this meta-analysis, along with the personal experience of many practitioners treating children and adolescents with obesity, it appears that one likely reason that there is “insufficient evidence” is that there are only limited studies that have been published.

We are also left with two additional questions: are these medications needed long-term, and are they safe and effective in younger children? The limited data available currently suggests that discontinuation of anti-obesity medication leads to substantial weight regain. However further studies are needed in children and adolescents and after a longer intervention period. We look forward to the outcomes of the ongoing pediatric RCTs including Liraglutide in children aged 6-11 years, Semaglutide in ages 6-17 years, and Phentermine in ages 10-17 years.