medwireNews: Results from a small case series in Denmark suggest sodium-glucose cotransporter (SGLT)2 inhibitors could be a useful add-on therapy for people with maturity-onset diabetes of the young (MODY)3.
There are different types of MODY, which is estimated to account for 1–2% of people with diabetes. Caused by inherited mutations in up to 14 known or suggested genes, some forms are more serious and others do not even require treatment, explained presenting researcher Henrik Maagensen, (Steno Diabetes Center Copenhagen, Denmark) at the 82nd ADA Scientific Sessions in New Orleans, Louisiana.
He added MODY3 accounts for about 70% of all MODY cases. Individuals with this condition have a mutation in the HNF1A gene that causes the pancreas to produce less insulin than normal. Beta cell function does not normally deteriorate in these cases and the condition can be managed with oral diabetes drugs such as sulfonylureas.
“The risk of complications in these patients is similar to that of type 2 diabetes and therefore treatment is important,” commented Maagensen.
Despite sulfonylureas being the standard first-line treatment for individuals with MODY3, they are known to cause hypoglycemia, said Maagensen. With co-researchers, he has previously tested incretin therapies such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in MODY3 patients with some success, but not SGLT2 inhibitors.
There are potential advantages to SGLT2 inhibitors for those with complication-prone diabetes, noted Maagensen. “They are effective glucose-lowering agents, cause bodyweight loss, and protect from chronic kidney disease, heart failure, and major adverse cardiovascular events.”
To assess the potential of SGLT2 inhibitors as a possible treatment for MODY3, Maagensen and colleagues recruited seven people with the condition who had already been treated with other oral antidiabetic medications, primarily sulfonylureas or insulin. The participants were aged 52 years on average and, while their average glycated hemoglobin (HbA1c) was not overly high at 6.9% (51.9 mmol/mol), they were mostly overweight (mean BMI 27.1 kg/m2); all except one were already experiencing complications such as retinopathy, neuropathy, and cardiovascular disease.
All seven patients were given the SGLT2 inhibitor empagliflozin 10 mg/day as an add-on therapy and followed up for 3–7 months. At follow-up, the mean HbA1c was 6.1% (43 mmol/mol), ranging from 5.6% to 7.8% (38–62 mmol/mol), and had decreased by an average 1.1% (12 mmol/mol) from baseline. The participants had also lost an average 3.4 kg in weight (0.8–13.8 kg).
Notably, at baseline there were four individuals treated with insulin at an average dose of 20 IU and this reduced significantly to three individuals on a dose of 3 IU after 6 months of treatment with empagliflozin.
No severe side effects were observed over a median follow-up of 1.2 years, but two patients developed urinary tract infections and one polyuria, all of which were thought to be linked to SGLT2 treatment.
As this study is very small, more research is needed to confirm the study findings, said Maagensen. “We are planning to do a randomized control trial to confirm that SGLT2 inhibitors can lower plasma glucose in these patients,” he explained.
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