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)

Diabetes Care. 2020 Sep;43(9):2025-2033. doi: 10.2337/dc20-0408. Epub 2020 Jul 13.

Abstract

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Glucose Self-Monitoring
  • Cross-Over Studies
  • Denmark
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced
  • Linagliptin / administration & dosage*
  • Linagliptin / adverse effects*
  • Male
  • Middle Aged
  • Placebos
  • Sulfonylurea Compounds / administration & dosage*
  • Sulfonylurea Compounds / adverse effects*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Placebos
  • Sulfonylurea Compounds
  • Linagliptin
  • glimepiride

Supplementary concepts

  • Mason-Type Diabetes

Associated data

  • EudraCT/2017-000204-15
  • figshare/10.2337/figshare.12515230