Glucagon-Like Peptide 1 Receptor Agonist in Diabetes Mellitus Management in Children and Adolescents With Transfusion-Dependent Thalassemia

Glucagon-Like Peptide 1 Receptor Agonist in Diabetes Mellitus Management in Children and Adolescents With Transfusion-Dependent Thalassemia

Blood transfusion and iron-chelation therapy have prolonged and improved the quality of life in patients with β-thalassemia. The improvement was mainly due to the decrease in mortality from heart failure Such a treatment, however, leads to chronic iron overload and frequently to endocrine complications, especially the development of diabetes.

The prevalence of diabetes mellitus (DM) in β-thalassemia varies from 9.7% to 29% and the overall prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) is 17.2% and 12.4% respectively in transfusion dependent thalassemia (TDT) patients.

GLP-1 is a proglucagon derived peptide that is released from gut endocrine cells in response to nutrient intake. This molecule is rapidly inactivated by the action of dipeptidyl peptidase IV (DPP-4) which limits its use as therapeutic agent.

Recent guidelines by the American Diabetes Association and the European Association for the Study of Diabetes recommend that for patients with type 2 diabetes, GLP-1 receptor agonists (GLP-1RAs) are preferable to insulin as the initial injection therapy and are also the preferred choice for addition to basal insulin for combination injection therapy.

An increasing number of clinical trials of agents in youth-onset T2D resulted in the availability of more efficacy data and regulatory approval for two Glucagon-like peptide-1 (GLP-1) receptor agonists (Liraglutide and Exenatide) in Pediatrics.

The Efficacy of the daily GLP-1 agonist, Liraglutide, in youth-onset T2D wasstudied in the Ellipse trial, which demonstrated placebo-subtracted. HbA1c lowering of 1% and 1.5% at 26 and 52 weeks, respectively. This glycemic reduction was accompanied by a small decrease in BMI z-score. Liraglutide (Victoza 0.6-1.8 mg a day) subsequently received approval by the FDA for use in youth 12-17 years of age.

Recently, extended release exenatide (Bydureon BCise 2 mg) was approved as a once-weekly injection for youth 10-17 years of age based on data from the BCB114 study showing superiority to placebo in lowering HbA1c with a between-group difference of 0.85 percentage points.

Hence, the aim of this study is to assess the efficacy and safety of GLP-1 receptor agonist versus conventional insulin therapy in the management of diabetes mellitus in children with transfusion -dependent Thalassemia.

Inclusion Criteria:

1. Age 10-18 years old.
2. Children with TDT according to the Thalassemia International Federation (TIF) guidelines (Farmakis et al., 2022).
3. Children with diabetes mellitus according to the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2022 guidelines (Libman et al., 2022).

Exclusion Criteria:

1. Other hemoglobinopathies as alpha thalassemia or sickle thalassemia patients.
2. Other disorders that may affect glucose homeostasis rather than β-TM.
3. Autoimmune disease, collagen diseases, hypo- or hyper-thyroidism, infections, tumors, hematological diseases other than β-TM.
4. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2).
5. Intake of any vitamins or food supplements one month before study and participation in a previous investigational drug study within the three months preceding screening.