Effects of Glimepiride Up-titration on Continuous Glucose Monitoring Metrics in Patients with HNF1A- or HNF4A-MODY

The primary objective is to evaluate the effects of glimepiride up-titration on continuous glucose monitoring (CGM) metrics in patients diagnosed with maturity-onset diabetes of the young type 3 (HNF1A-MODY) or maturity-onset diabetes of the young type 1 (HNF4A-MODY), including those previously managed under classifications of type 1 diabetes or type 2 diabetes. This assessment is clinically relevant to determining the impact of sulfonylurea dose escalation on glycemic control within these specific genetic phenotypes. Therapy (3).

The sponsor did not provide information regarding the total number of participants. The study population consists of patients diagnosed with Maturity-onset diabetes of the young type 3 or Maturity-onset diabetes of the young type 1. The participants include both males and females within the age range of 18 to 45 years. Inclusion requires a heterozygous mutation in the HNF1A or HNF4A gene that is classified as pathogenic or likely pathogenic according to ACMG criteria. Eligible individuals must exhibit an HbA1c level of ≥48 mmol/mol and/or be receiving current insulin treatment. This cohort may include individuals previously identified as having type 1 diabetes or type 2 diabetes.

This phase 4 clinical trial involves the systematic assessment of glimepiride up-titration in individuals diagnosed with maturity-onset diabetes of the young type 3 or maturity-onset diabetes of the young type 1. The study evaluates the effects of sulfonylurea titration on continuous glucose monitoring metrics. The research methodology focuses on determining the mean difference in time in tight range measured via CGM between a two-week baseline period and the final two weeks of the intervention. Secondary endpoints include changes in haemoglobin A1c, mean glucose, coefficient of variation, standard deviation, and various metrics regarding hypoglycaemic events. The study aims to delineate optimal use and safety profiles for the medication in this specific population. Participation involves a screening process to confirm eligibility based on heterozygous mutation status in the HNF1A-gene or HNF4A-gene, an HbA1c level ≥48 mmol/mol, and age requirements.

The experimental treatment consists of glimepiride administered in a PHF00245MIG pharmaceutical form. The medicinal product is provided for oral use at a dosage of 3 mg. This intervention is evaluated for its effects on continuous glucose monitoring metrics in patients diagnosed with maturity-onset diabetes of the young (MODY) caused by mutations in HNF1A or HNF4A.

The primary efficacy endpoint is the mean difference in time in tight range (3.9–7.8 mmol/l) as measured by continuous glucose monitoring (CGM) during a two-week period at baseline and the final two weeks of the intervention. Secondary endpoints include assessments of various CGM-metrics, specifically mean glucose, coefficient of variation (CV%), standard deviation (SD), percentage of time in range (3.9–10 mmol/l), and percentage of time above range (>10 mmol/l), all evaluated at baseline and in the last two weeks of the intervention.

Additional secondary parameters involve the mean difference in haemoglobin A1c (HbA1c), total plasma glucose AUC, and total plasma C-peptide AUC obtained from an oral glucose tolerance test (OGTT). Clinical outcomes also include the mean time to cease sulfonylurea (SU) titration, the mean tolerable dose of SU, and changes in body mass index (BMI), waist-to-height ratio, and body fat mass. Efficacy is further assessed through the proportion of individuals requiring insulin treatment and the mean difference in daily insulin doses for those treated at baseline. Safety and glycemic control are monitored via the rate ratio and proportion of hypoglycaemic events, categorized by severity and study phase, utilizing both CGM and participant-reported data, as well as the mean difference in the percentage of time glucose levels remain below 3.9 mmol/l and 3.0 mmol/l.