Effect of SGLT2 Inhibition on Glucosuria During a Hyperglycemic Clamp in HNF1A-MODY (MODY3) and Type 2 Diabetes
Abstract
OBJECTIVE: Pathogenic variants of HNF1A cause maturity-onset diabetes of the young type 3 (HNF1A-MODY; also known as MODY3). Individuals with HNF1A-MODY are primarily treated with sulfonylureas; however, little is known about the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in HNF1A-MODY. Interestingly, HNF1A-MODY is associated with increased glucosuria, which has been attributed to lower expression of SGLT2 as observed in HNF1A-knockout mice. We investigated the impact of acute SGLT2 inhibition on glucosuria in individuals with HNF1A-MODY or type 2 diabetes.
RESEARCH DESIGN AND METHODS: In a randomized, double-blind, crossover study, individuals with HNF1A-MODY or type 2 diabetes underwent two three-step hyperglycemic clamps targeted at 1-h periods of 10, 14, and 18 mmol/L glucose with and without acute SGLT2 inhibition (25 mg empagliflozin or placebo administrated 2 h before clamp procedures).
RESULTS: Eleven individuals with HNF1A-MODY (age [mean ± SD] 49 ± 15 years; glomerular filtration rate [GFR; mean ± SD] 113 ± 18 mL/min) and 10 individuals with type 2 diabetes (age 63 ± 7 years; GFR 103 ± 27 mL/min) were included. During the 3-h hyperglycemic clamp, SGLT2 inhibition increased urinary glucose excretion in both groups (HNF1A-MODY: 24.5 g [95% CI 20.6, 28.3]; type 2 diabetes: 23.5 g [95% CI 20.4, 26.5]). The effect of SGLT2 inhibition was not significantly different between the groups (1.0 g [95% CI -3.5, 5.6]; P = 0.6).
CONCLUSIONS: The robust effect of…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 10 participants or records.
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