Efficacy and Safety of Glimepiride with or without Linagliptin Treatment in Patients with HNF1A-diabetes (Maturity Onset Diabetes of the Young Type 3): A Randomized, Double-blinded, Placebo-controlled, Crossover Trial (GLIMLINA)

OBJECTIVE <p>Sulfonylureas are first-line treatment of hepatocyte nuclear factor 1-alpha (HNF1A)-diabetes [maturity onset diabetes of the young type 3], but many patients do not achieve optimal glycemic control without episodes of hypoglycemia. We investigated the combination of the sulfonylurea, glimepiride, and the dipeptidyl peptidase-4 inhibitor, linagliptin, versus glimepiride monotherapy with respect to glycemic variability, glycemic control and risk of hypoglycemia.</p> <p>RESEARCH DESIGN AND METHODS </p> <p>In a randomized, double-blinded, crossover trial, patients with HNF1A-diabetes (<i>n</i> = 19, [mean ± SD]; age: 43 ± 14 years; BMI 24.8 ± 2.8 kg/m²; <a>glycated hemoglobin (HbA_1c) </a>7.4 ± 0.2% [57.1 ± 7.3 mmol/mol]) were randomly assigned to treatment with glimepiride + linagliptin 5 mg (16 weeks), wash-out (4 weeks) and glimepiride + placebo (16 weeks) (or vice versa). Glimepiride was titrated targeting a fasting plasma glucose of 4.5-6.0 mM without hypoglycemia. Treatments were evaluated by continuous glucose monitoring (CGM), HbA_1c and meal test. </p> <p>RESULTS</p> <p><a></a><a>Compared to glimepiride + placebo, glimepiride + linagliptin did not significantly improve the primary endpoint mean amplitude of glycemic excursions </a>(MAGE) ([mean difference] -0.7 mM, <i>P</i> <i>= </i>0.1540) but displayed significant reductions in coefficient of variation (CV) on CGM (-3.6%, <i>P</i> <i>= </i>0.0401), HbA_1c (-0.5%, <i>P</i> <i>= </i>0.0048) and glimepiride dose (-0.7 mg/day, <i>P</i> <i>= </i>0.0099). Beta cell glucose sensitivity (assessed as C-peptide:glucose) during meal test improved with glimepiride + linagliptin. Incidences of hypoglycemia were similar with both treatments. </p> <p>CONCLUSION </p> <p>Linagliptin as add-on treatment to glimepiride improved glycemic variability and control without increasing risk of hypoglycemia in patients with HNF1A-diabetes. </p>