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October 31, 2023

Pediatric Research Update | Anti-obesity pharmacotherapy for treatment of pediatric type 2 diabetes: Review of the literature and lessons learned from adults

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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 addresses anti-obesity pharmacotherapy for treatment of pediatric type 2 diabetes.

Anti-obesity pharmacotherapy for treatment of pediatric type 2 diabetes: Review of the literature and lessons learned from adults

Article Summary

This article discusses the available evidence of anti-obesity medications (AOMS) in treatment of type 2 diabetes in adolescents, including literature review of type 2 diabetes in adults. Read the article here.

Article Review

This article emphasizes the growing data regarding the increasing number of pediatric patients diagnosed with type 2 diabetes mellitus (T2DM). More concerningly, T2DM in children progresses more rapidly, and is associated with higher rates of microvascular complications compared to adults. Having obesity (BMI of ≥ 95% for age and sex) increases risk for T2DM. The American Diabetes Association (ADA) has recommended a 7-10% weight reduction. Unfortunately, Metformin plus lifestyle management, the first line of therapy, rarely results in significant BMI reduction. Data from Treatment Options for T2DM for Adolescents and Youth (TODAY) study revealed that half of youth with T2DM progressed to insulin dependence after close to a year of Metformin and lifestyle management. Metformin also has not been shown to reduce beta cell deterioration which may be the reason behind worsening glycemic control over time of adult and youth with T2DM.

The authors presented the available anti-obesity pharmacotherapy in adults with type 2 diabetes and obesity. They also reviewed medications available for pediatrics and the clinical trials done. Of note, BMI reduction is used for pediatrics and weight reduction is used for adults.

Phentermine/ Topiramate (PHN/TPM) is approved for ages 12 and above. No published clinical trial for adolescents with T2DM, but clinical trials of pediatrics with mean BMI of 37.8 kg/m2showed mean BMI reduction of 7.1% on top-dose PHEN/TPM (15 mg/92 mg per day). Triglycerides also decreased by 12%. Adult with T2DM and overweight/ obesity had 2 RCTs that show 8-10% weight reduction as well as achieving an A1c < 6.5% with top dose of PHN/TPM.

Glucagon-like peptide-1 receptor agonist (GLP1-RA) such as Liraglutide 3mg/day had clinical trial done for adolescents with and without T2DM that showed BMI reduction of more than 10 percent. There was no significant reduction in A1c but only 2 patients with T2DM were enrolled. In adults, Liraglutide at 3mg/day showed weight reduction by 6% and A1c reduction by 1.3 percent. At the time the article was written, the other GLP1-RA, Semaglutide 2.4mg weekly was not yet approved for pediatrics. Clinical trials in adults with T2DM and obesity showed weight reduction of more than 10 percent. Although there is no mention of improvement in A1c, the author mentioned that anti-diabetes medications were reduced or discontinued more often in participants receiving the medications than placebo.

Neither Orlistat nor Naltrexone/ bupropion (NB) have trials done in pediatrics with type 2 diabetes but both show weight reduction in adult with T2DM and obesity. NB also showed A1c reduction of more than 7%.

This article demonstrates the lack of data in pediatric obesity and T2DM. More clinical trials are needed with AOMS and adolescents with T2DM. Clinical trials data in adults showed at least 7% weight reduction in three AOMS, two of which FDA approved for pediatric obesity. With the recent approval of Semaglutide 2.4mg weekly in pediatric obesity, and the significant BMI reduction seen, there is more to learn. Bariatric surgery remains an effective treatment for both T2DM and obesity in adolescents. In sum, given the relationship between obesity and T2DM and the concern for persistence of childhood obesity and T2DM to adulthood, it’s important to continue to identify treatments to mitigate worsening obesity.

Additional Resources

Find more resources curated by OMA’s Pediatric Committee on our Pediatric Resources page. There you’ll find additional article reviews on various topics related to obesity as well as public resources for clinicians and families.

Bensignor MO, Kelly AS, Arslanian S. Anti-obesity pharmacotherapy for treatment of pediatric type 2 diabetes: Review of the literature and lessons learned from adults. Front Endocrinol (Lausanne). 2022 Oct 27;13:1043650. doi: 10.3389/fendo.2022.1043650. PMID: 36387846; PMCID: PMC9647073.