Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader–Willi Syndrome: A Case Report
Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader-Willi Syndrome: A Case Report
Masayo Kagami . Maki Fukami . Jun Takeda 0 1 2
0 M. Kagami M. Fukami Department of Molecular Endocrinology, National Research Institute for Child Health and Development , 2-10-1 Okura, Setagaya, Tokyo 157- 8535 , Japan
1 Y. Horikawa M. Enya K. Hashimoto J. Takeda Division of Clinical Genetics, Gifu University Hospital , 1-1 Yanagido, Gifu 501-1194 , Japan
2 Y. Horikawa (&) M. Enya M. Komagata K. Hashimoto J. Takeda Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine , 1-1 Yanagido, Gifu 501-1194 , Japan
Introduction: Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS. Case Report: A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age. At age 16 years, he was diagnosed with diabetes and began to take several kinds of oral hypoglycemic agents. At age 29 years, his BMI was 39.1 kg/m2 and he was referred to our department for diabetes and obesity treatment. In the present case, the HbA1c was not improved by GLP-1RAs despite a 28-kg BW reduction, which included a 9-kg loss of muscle. Apprehensive of further loss of muscle mass, basal insulin of insulin glargine was administered in addition to GLP-1RAs. Immediately after the addition of tofogliflozin, a sodiumglucose cotransporter-2 (SGLT2) inhibitor, the patient's HbA1c decreased dramatically with only about an additional 3% BW reduction. We note an improvement in our case of lipid deposition in the pancreas confirmed by abdominal CT after the improvement of HbA1c. It is unknown whether this improvement of fatty pancreas was a cause or an effect of the improved glycemic control in the present case. Conclusion: This finding clearly supports the effectiveness of combining SGLT2 inhibitors with GLP-1RAs for treatment of patients with PWS and non-alcoholic fatty pancreas disease.
Prader-Willi syndrome (PWS); Sodium-glucose cotransporter-2 (SGLT2) inhibitor; GLP-1 receptor agonists (GLP-1RAs); Non-alcoholic fatty pancreas disease (NAFPD)
INTRODUCTION
Prader–Willi syndrome (PWS) is a complex
multisystem genetic disorder with an incidence
of one in 10,000–15,000 live births in Japan.
PWS is an imprinting disorder that arises from
lack of expression of paternally inherited genes
on chromosome 15q11-q13. The syndrome has
a characteristic phenotype that includes
neonatal hypotonia, hyperphagia,
hypogonadism, obesity, short stature, and cognitive
and behavioral disabilities. In adult PWS, the
most difficult to treat feature is morbid obesity
due to hyperphagia caused by an absence of
satiety and decreased energy expenditure.
Severe obesity increases risk of developing diabetes
mellitus [1–3]. While diet therapy is
fundamentally important in the treatment of
diabetes, it is problematic in patients with PWS,
and requires use of insulin and other injected
drugs as well as oral medications. During the
last decade, many new medicines for treating
diabetes have become available, but there are as
yet no guidelines on these drugs for adult
patients with PWS. This is the first report of the
effectiveness of a sodium-glucose
cotransporter2 (SGLT2) inhibitor as an add-on drug to GLP-1
receptor agonists (GLP-1RAs) for glycemic
control of adult patients with PWS.
A 36-year-old Japanese male patient was born at
36 weeks’ gestation via vaginal breech delivery.
He had newborn asphyxia and an Apgar score of
4. Because of hypotonia, his height could not be
measured and his weight was 2150 g. At the age
of 10 years he was diagnosed with PWS on the
basis of typical clinical findings including being
a floppy infant and having almond shaped eyes,
scoliosis, obesity (weight more than 20% of
standard), mental retardation (IQ of 61), and
hypogonadism with bilateral cryptorchidism.
At age 12 years, he was referred to a pediatric
endocrinologist for assessment of his pituitary
function and glucose tolerance. Oral glucose
and insulin tolerance test showed impaired
glucose tolerance (IGT) and little reaction of
growth hormone. GH therapy was not done
because of the IGT level and severe obesity. At
age 16 years, he was diagnosed with diabetes
and began to take several kinds of oral
hypoglycemic agents.
At age 28 years, he was referred to our
department of diabetes and endocrinology for
diabetes and obesity treatment. At that time, he
was obese with body weight of 90.6 kg, height
of 152.2 cm, and BMI of 39.1 kg/m2. He showed
no sign of diabetic retinopathy but he had
microalbuminuria (13.6 mg/gCr). Despite
having been treated with glibenclamide
(1.25 mg/day), metformin (1000 mg/day), and
pioglitazone (15 mg/day), his HbA1c (...truncated)