Prader-Willi syndrome (PWS) is one of the most commonly recognized causes of early-onset
childhood obesity. Individuals with PWS have significant
hyperphagia and decreased recognition of satiety. The exact etiology of the
hyperphagia remains unknown and, therefore, untreatable. We conducted a pilot, open-label study of response to
metformin in 21 children with PWS and six with early
morbid obesity (EMO). Participants had significant
insulin resistance and
glucose intolerance on oral
glucose tolerance testing (OGTT) and were started on
metformin for these biochemical findings. We administered the
Hyperphagia Questionnaire to parents of patients before and after starting
metformin treatment. Both the PWS and EMO groups showed significant improvements in food-related distress, anxiety, and ability to be redirected away from food on the
Hyperphagia Questionnaire. In the PWS group, improvements were predominantly seen in females. Within the PWS group, responders to
metformin had higher 2-h
glucose levels on OGTT (7.48 mmol/L vs. 4.235 mmol/L; p=0.003) and higher fasting
insulin levels (116 pmol/L vs. 53.5 pmol/L; p=0.04). Additionally, parents of 5/13 individuals with PWS and 5/6 with EMO reported that their child was able to feel full while on
metformin (for many this was the first time they had ever described a feeling of fullness).
Metformin may improve sense of satiety and decrease anxiety about food in some individuals with PWS and EMO. Positive response to
metformin may depend on the degree of
hyperinsulinism and
glucose intolerance. Nonetheless, the results of this pilot study bear further investigation.