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Type 2 diabetes mellitus (T2DM) in adolescents is a more rapidly progressive disease, associated with earlier and higher rates of microvascular complications than in adults. As obesity is a significant risk factor for T2DM development and progression, the American Diabetes Association (ADA) recommends anti-obesity medications (AOMs) as adjuvant therapy for adults with both T2DM and overweight/obesity. In adults, the addition of AOMs to a diabetes regimen can improve glycemic control, reduce weight, and decrease anti-diabetes medication use. The ADA recommends considering bariatric surgery for adolescents with T2DM who have a BMI >35 kg/m 2 , but did not mention the use of AOMs in their 2022 updated guidelines. Currently, there are three FDA-approved AOMs available for chronic use in adolescents with obesity. Other medications are used in an "off-label" fashion for appetite suppression and BMI reduction. As additional AOMs are being developed and FDA-approved for the pediatric population, new treatment options with novel mechanisms of action will become available for adolescents with T2DM and obesity. In this review, we will discuss the evidence for the use of AOMs in the treatment of T2DM in adolescents, including lessons learned from the adult T2DM literature., Competing Interests: AK engages in unpaid consulting and educational activities for Novo Nordisk, Vivus, Eli Lilly, and Boehringer Ingelheim as well as receives donated drug/placebo from Vivus and Novo Nordisk for National Institute of Diabetes and Digestive and Kidney Diseases-funded clinical trials. SA receives grant support from and serves as a consultant for AZ DMC, Novo and Lilly. MB receives research support Vivus Inc and Novo Nordisk., (Copyright © 2022 Bensignor, Kelly and Arslanian.)

Objective: This study sought to evaluate the effect of 52 weeks of exenatide extended release (XR) on the maintenance of meal replacement therapy (MRT)-induced BMI reduction in adolescents with severe obesity., Methods: In this randomized, double-blind, placebo-controlled trial, 100 participants aged 12 to 18 years with BMI ≥ 1.2 × 95th percentile were enrolled in a short-term MRT run-in phase. Those who achieved ≥5% BMI reduction during the run-in were then randomized to 52 weeks of exenatide XR 2.0 mg or placebo weekly. Both groups also received lifestyle therapy. The prespecified primary end point was mean percent change in BMI from randomization (post run-in) to 52 weeks in the intention-to-treat population., Results: A total of 100 participants were enrolled, and 66 (mean age 16 = [SD 1.5] years; 47% female) achieved ≥5% BMI reduction with MRT and were randomized (33 to exenatide XR and 33 to placebo). From randomization (post run-in) to 52 weeks, mean BMI increased 4.6% and 10.1% in the exenatide XR and placebo groups, respectively. The placebo-subtracted exenatide XR treatment effect was -4.1% (95% CI: -8.6% to 0.5%, p = 0.078)., Conclusions: Although not achieving statistical significance, exenatide XR, compared with placebo, may partly mitigate the propensity toward BMI rebound in adolescents who achieved initial weight loss with dietary intervention., (© 2022 The Obesity Society.)