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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)

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posted on 13.07.2020 by Alexander S. Christensen, Sofie Hædersdal, Julie Støy, Heidi Storgaard, Ulla Kampmann, Julie L. Forman, Marta Seghieri, Jens J. Holst, Torben Hansen, Filip K. Knop, Tina Vilsbøll
OBJECTIVE

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.

RESEARCH DESIGN AND METHODS

In a randomized, double-blinded, crossover trial, patients with HNF1A-diabetes (n = 19, [mean ± SD]; age: 43 ± 14 years; BMI 24.8 ± 2.8 kg/m2; glycated hemoglobin (HbA1c) 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), HbA1c and meal test.

RESULTS

Compared to glimepiride + placebo, glimepiride + linagliptin did not significantly improve the primary endpoint mean amplitude of glycemic excursions (MAGE) ([mean difference] -0.7 mM, P = 0.1540) but displayed significant reductions in coefficient of variation (CV) on CGM (-3.6%, P = 0.0401), HbA1c (-0.5%, P = 0.0048) and glimepiride dose (-0.7 mg/day, P = 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.

CONCLUSION

Linagliptin as add-on treatment to glimepiride improved glycemic variability and control without increasing risk of hypoglycemia in patients with HNF1A-diabetes.

Funding

The study was funded by an unrestricted grant from Boehringer Ingelheim, Copenhagen, Denmark.

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