Endocrine Abstracts

Introduction: Prader-Willi syndrome is a multi-system disorder that commonly leads to severe obesity. Hyperphagia plays a key role in the development of obesity and without restriction of calorie intake patients will often develop severe obesity related complications including an increased risk of type 2 diabetes (T2DM). GLP-1 receptor agonists (GLP1-RA) have been developed for use in obesity and T2 DM for weight loss and glycaemic control as well as cardiometabolic positive outcomes. They have been shown to decrease appetite through increased satiety and have been demonstrated as being effective in cases of hypothalamic obesity.

Case history: A 25 year old male with a background of Prader-Willi like syndrome (history of obesity, hyperphagia and developmental delay) was diagnosed with type 1 diabetes (T1DM) aged 18 (Glutamic Acid Decarboxylase and Zinc transporter 8 antibody positive). He was treated with a basal bolus regime, however, due to evidence of insulin resistance (with acanthosis nigricans, hypertriglyceridemia and low HDL) he was started on metformin. Despite this he had continuous excessive weight gain, exacerbated by persistent hyperphagia. At 23 years old he had a BMI 44.95 kg/m², HbA1 c 70 mmol/mol, total daily insulin dose 149 units (1.4 units/kg). He also had evidence of mild sleep apnoea on sleep studies. Despite lifestyle changes with diet and exercise, he had limited weight loss. Consequently, he was commenced on a trial of a GLP1-RA both for glycaemic control, weight loss and appetite suppression. Due to intolerance with Dulaglutide, he was trialled on Liraglutide with the dose up titrated to 1.8 mg daily.

Results and management: Treatment with a GLP1-RA resulted in reported appetite suppression. Additionally, there was a 14% reduction in weight with BMI improving to 37.7 kg/m² following 14 months of treatment. Glycaemic control also improved (HbA1 c 46 mmol/mol), with a reduction in insulin requirement independent of weight loss (total daily insulin dose 92 units (1.0 unit/kg))

Conclusion: This case demonstrates the efficacious use of a GLP1-RA in a patient with T1 DM and Prader-Willi like syndrome with evidence of insulin resistance and morbid obesity. Use of Liraglutide led to significant weight loss and improvement in insulin sensitivity with a self-reported improvement in hyperphagia. The use of GLP1-RA agonists should be considered in patients in syndromic obesity and diabetes, where weight reduction is an important factor in reducing long term metabolic complications.