Diabetes medications may support kidney health in adults with PWS
Study reports blood sugar and kidney benefits, with close monitoring advised
Sodium-glucose cotransporter-2 inhibitors (SGLT2is), a class of type 2 diabetes medications, may help improve blood sugar levels and support kidney health markers in adults with Prader-Willi syndrome (PWS) and type 2 diabetes, according to a study in France.
Despite these benefits, the treatment did not lead to significant weight changes, which differs from what is typically seen in people with obesity and type 2 diabetes.
In addition, SGLT2is were linked to higher rates of adverse events, including acute kidney injury requiring hospitalization, than seen in the broader type 2 diabetes population.
These findings suggest that although these medications may effectively treat diabetes in people with PWS, “close safety monitoring is warranted, particularly regarding [kidney] function,” the researchers wrote.
The study, “Glycemic and renal effects of SGLT2 Inhibitors in Prader-Willi syndrome: Benefits and risks,” was published in Diabetes & Metabolism.
Understanding PWS and type 2 diabetes
PWS is a complex genetic condition marked by symptoms such as excessive hunger, obesity, hormone-production changes, intellectual disability, and behavioral challenges.
About 20% of people with PWS develop type 2 diabetes. This happens when the body becomes resistant to insulin, a hormone that regulates blood sugar, or can’t make enough of it, leading to high blood sugar levels.
“However, standard diabetes management is particularly challenging in this population due to both metabolic and behavioral specificities,” the researchers wrote.
SGLT2is, medications primarily used for type 2 diabetes, lower blood sugar by helping the body remove extra glucose through the urine. They can also promote weight loss and support heart and kidney health. However, “their use in PWS remains largely unexplored,” the researchers wrote.
To learn more, the researchers analyzed data from 48 adults with PWS and type 2 diabetes who took part in an observational study (NCT04604626) at several centers in France.
Half were treated with SGLT2i, while the other half were not and served as the control group. Both groups were similar in sex, age, and diabetes duration. However, more people in the SGLT2i group had a deletion, the most common type of PWS-causing mutation (75% vs. 50%).
How PWS affects health and diabetes risk
At the start of the study, diabetes appeared more severe in the SGLT2i group, who had higher HbA1c levels (8.8% vs. 6.9%). HbA1c measures how much blood sugar is attached to hemoglobin — the protein that carries oxygen in red blood cells — and reflects average blood glucose levels over the past two to three months.
The SGLT2i group also showed signs of more advanced kidney involvement, suggested by a trend toward higher urinary albumin-to-creatinine ratio (UACR), a marker of kidney damage.
Patients treated with SGLT2is for about six months had significant drops in HbA1c and UACR, along with a modest reduction in blood pressure during heart contraction, compared with the control group. Estimated glomerular filtration rate, a measure of kidney function, remained stable in both groups.
This “suggests early [kidney] protection consistent with the known SGLT2i mechanisms,” the researchers wrote.
However, these effects “occurred without significant changes in body weight, indicating weight-independent benefits,” the researchers wrote.
Why diabetes is common in adults with PWS
Further analyses showed that baseline HbA1c, SGLT2i use, and insulin treatment at six months were independent predictors of HbA1c variation.
Overall, 37.5% of the adults in the SGLT2i group experienced treatment-related adverse events. The most common were fungal infections (16.6%), hypovolemia-related symptoms such as dizziness or low blood pressure (16.5%), and acute kidney injury requiring hospitalization (8.3%).
Rates of serious acute kidney injury were higher than those reported in earlier SGLT2i studies in the general type 2 diabetes population. While SGLT2is are “described as long-term protectors against AKI [acute kidney injury],” people with PWS “have an increased risk of AKI compared with the general population,” the team wrote.
Here, “SGLT2is seemed to be more frequently prescribed to patients with more advanced [kidney] impairment, as suggested by the trend toward higher baseline UACR levels in the treated group,” they added.
According to the researchers, “SGLT2is may offer valuable [blood sugar] and [kidney] benefits in adults with PWS and [type 2 diabetes]. However, due to the elevated risk of adverse events, careful monitoring of [kidney] function, volume status, and co-medications is essential.”
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