Acquired Brain Injury-Induced Hyperphagia and Obesity, Successfully Treated With a GLP-1 Agonist

Background: Several Glucagon-like peptides 1 (GLP-1s) were approved since 2005 for the treatment of DM & obesity. Their usefulness in other conditions is not well studied. We present two cases of hyperphagia after TBI successfully treated with GLP-1 agonists. Clinical cases: Case 1: A 54-year-old female with a history of multiple traumatic brain injuries (multiple falls and a ski accident) complained of years of insatiable hunger leading to hyperphagia and over 20 pounds weight gain. With tremendous will-power, she avoided additional weight gain by adopting a strict meal-plan and increasing her water intake (10–12 liters a day) to relieve her hunger. She sipped so much water, that her sodium remained 123 - 133 mmol/L (ref: 135–146) with dilute urine. Initial tests revealed: IGF-1 315 ng/ml (52–328), FSH 77.5 mIU/ml (23–116.3), LH 24.3 mIU/ml (14.2–52.3), prolactin 17.1 ng.ml (10–54.7), estradiol 17 (<31), TSH 1.09mIU/ml (0.45–4.5), FT4 1.0 ng/dl(0.8–1.8), all within the normal limit for her age. Semaglutide 0.25mg/week was started and increased to 0.5mg/week. Within the first six months of treatment, she experienced 22 pounds of weight loss, hunger relief, less water sipping behavior, and more enjoyment of food. Her sodium rose to 137 mmol/L. Case 2: A 40-year-old female, s/p craniectomy and aneurysm clipping due to intracranial hemorrhage complicated by an ischemic stroke developed sudden, documented, 45-pound weight gain over thirteen months despite aggressive lifestyle modification attempts. Initial labs revealed: TSH 1.33 mIU/ml (0.45–4.5), FT4 1.22 ng/dl (0.8–1.8), midnight salivary cortisol 0.03 mcg/dl (<0.09), ruling out hypothyroidism and Cushing syndrome. Liraglutide 1.8mg/day was started and has resulted to date in 26 pounds (11.8% of maximum weight) by 9 months with an associated decrease in subjective hunger. Conclusion: Hyperphagia can be seen in brain injury, in response to some medications, and some genetic conditions, like Prader-Willi. The exact mechanisms are not clear am may be multifactorial. In the case of brain injury, proposed mechanisms include insatiable hunger due to ventromedial hypothalamic or brain stem dysfunction, or disinhibition and poor impulse control due to frontal lobe injury. GLP-1’s may act on the causal mechanism for increased hunger, or it may result in clinical improvement through a parallel pathway. More studies are warranted to investigate the application of GLP-1’s to hyperphagia.