Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained traction for the management of type 2 diabetes and obesity. Unlike several classes of antidiabetic medications that contribute to weight gain, GLP-1RAs not only reduce haemoglobin A1c, but also promote weight loss. While there is a large body of evidence supporting its safety and efficacy in adults, paediatric clinical trial data have only emerged in recent years. This review will discuss the limited treatment options for paediatric type 2 diabetes and the mechanism of action of GLP-1RAs as it pertains to physiological pathways relevant for type 2 diabetes, obesity and their related comorbidities. The outcomes of paediatric trials evaluating liraglutide, exenatide, semaglutide and dulaglutide in paediatric type 2 diabetes and obesity will be closely examined, including differences compared with adult studies. Finally, potential barriers and strategies to expanding GLP-1RA access in adolescents will be discussed. Future studies are needed to determine if the cardio- and renal-protective benefits of GLP-1RAs apply to youth-onset type 2 diabetes.
Introduction: Time limited eating (TLE) improves β-cell function, increases insulin sensitivity, lowers fasting glucose, and increases time in range in adults with T2D. Objectives: This study aims to evaluate TLE in pediatric new-onset T1D, at which time residual β-cell function may be preserved. Aim 1) Evaluate feasibility, acceptability, and safety of TLE. Aim 2) Test impact of TLE on β-cell function and insulin sensitivity. Aim 3) Assess effectiveness of TLE on glycemic control. Methods: A randomized controlled trial of youth aged 12-25 years diagnosed with T1D within 12 months; randomization to intervention (8-hour feed/16-hour fast) or control group (≥12-hour feed) for an 8-week period. Feasibility is evaluated using questionnaires and adherence. Safety is indicated by hypoglycemia frequency. β-cell function is evaluated by mixed meal tolerance test (MMTT) with area under C-peptide curve (AUC). Glycemic control is evaluated by time in range (TIR 70-180 mg/dL) on CGM and HbA1c. Results: Six youths have entered, three have completed (2 intervention, 1 control). Participants in intervention group adhered to TLE ~94% of time. Both reported TLE felt safe, noted improved stability of glucose, chose to continue TLE after study ended, and would recommend to others with T1D. No increased hypoglycemia frequency noted on CGM. Participant 2 (intervention) had increase in AUC from baseline (87.45 to 152.4) and decrease in HbA1c (-1.3 percentage points), although participant 1 (intervention) had decrease in AUC and no change in HbA1c. Participant 3 (control) had increase in AUC and decrease in HbA1c, both changes less than participant 2. No improvement in TIR on CGM was demonstrated in either group. Conclusion: This is the only known study evaluating TLE in youth with T1D and has the potential to advance management of T1D by introducing meal-timing early in diagnosis. Thus far the intervention appears feasible and safe, however more data is needed. Recruitment continues to be underway. Disclosure C.Berman: None. A.Vidmar: Advisory Panel; Rhythm Pharmaceuticals, Inc., Research Support; Dexcom, Inc. J.J.Flores garcia: None. J.Raymond: None.
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