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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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DOI

  1. Trajectories of Childhood Adversity and Type 1 Diabetes: A Nationwide Study of One Million Children

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Antidiabetes Agents and Incident Depression: A Nationwide Population-Based Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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OBJECTIVE: Sulfonylureas are first-line treatment of hepatocyte nuclear factor 1-α (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, and 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), washout (4 weeks), and glimepiride + placebo (16 weeks) (or vice versa). Glimepiride was titrated targeting a fasting plasma glucose of 4.5-6.0 mmol/L without hypoglycemia. Treatments were evaluated by continuous glucose monitoring (CGM), HbA1c, and meal test.

RESULTS: Compared with glimepiride + placebo, glimepiride + linagliptin did not significantly improve the primary end point, mean amplitude of glycemic excursions (MAGE) (mean difference -0.7 mmol/L, P = 0.1540), but displayed significant reductions in coefficient of variation on CGM (-3.6%, P = 0.0401), HbA1c (-0.5%, P = 0.0048), and glimepiride dose (-0.7 mg/day, P = 0.0099). β-cell glucose sensitivity (assessed as C-peptide-to-glucose ratio) during meal test improved with glimepiride + linagliptin. Incidences of hypoglycemia were similar with both treatments.

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

OriginalsprogEngelsk
TidsskriftDiabetes Care
Vol/bind43
Udgave nummer9
Sider (fra-til)2025-2033
Antal sider9
ISSN1935-5548
DOI
StatusUdgivet - sep. 2020

Bibliografisk note

© 2020 by the American Diabetes Association.

ID: 61381668