Glycemic and Renal Effects of
SGLT2
Inhibitors in Monogenic Diabetes: A Real‐World National Study
Estelle Audrain, Pierre Bel Lassen, Christine Bellanné‐Chantelot, Marie Christine Vantyghem, Hippolyte Dupuis, Tiphaine Vidal‐Trecan, Nicolas Chevalier, Danièle Dubois‐Laforgue, Sophie Lamothe, Camille Vatier, Orianne Villard, René Valéro, Claire Briet, Corinne Vigouroux, Cécile Ciangura, Chloé Amouyal ABSTRACT
Aims
Evidence regarding the efficacy and safety of sodium–glucose cotransporter 2 inhibitors (SGLT2i) in monogenic diabetes is limited. We evaluated real‐world metabolic, renal, and safety outcomes of SGLT2i therapy in adults with monogenic diabetes.
Materials and Methods
This multicenter retrospective study included adults with genetically confirmed monogenic diabetes treated with SGLT2i. Clinical and biological data were collected at baseline and after approximately 1 and 2 years. Longitudinal changes were analysed using linear mixed‐effects models adjusted for baseline value, age, and sex and treatment intensification.
Results
Forty patients (mean age 48.6 ± 15.2 years) with MIDD ( n = 16), HNF1B ‐MODY ( n = 9), HNF1A/HNF4A ‐MODY ( n = 11), or other MODY subtypes ( ABCC8, INS, RFX6 ; n = 4) were followed for 23.9 ± 5.9 months. HbA1c remained stable overall but decreased significantly in patients with baseline HbA1c ≥ 8% (9.6% ± 1.3% to 7.6% ± 0.7%; p = 0.001). UACR declined significantly (−35.6% at 1 year and −43.5% at 2 years; p = 0.004), particularly in those with baseline CKD (trend). Genotype‐specific trends suggested greater glycemic improvement in HNF1A/HNF4A ‐MODY and greater UACR reduction in MIDD. eGFR declined modestly over time. Non‐serious adverse events occurred in 15% of patients, 7.5% discontinued treatment, and no ketoacidosis, acute kidney injury, or deaths were reported.
Conclusions
In this nationwide cohort of patients with monogenic diabetes—the largest reported to date—SGLT2i therapy was associated with improved glycemic control in individuals with baseline HbA1c ≥ 8%, reduced albuminuria, and showed a favourable safety profile. These findings support SGLT2i as a potential therapeutic option that warrants confirmation in larger controlled studies.