title: Glucose-lowering effects and low risk of hypoglycemia in patients with maturity-onset diabetes of the young when treated with a GLP-1 receptor agonist: a double-blind, randomized, crossover trial.
abstract: OBJECTIVE
  The most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1α (HNF1A diabetes: MODY3) is often treated with sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A diabetes.
  
  
  METHODS
  Sixteen patients with HNF1A diabetes (8 women; mean age 39 years [range 23-67 years]; BMI 24.9 ± 0.5 kg/m(2) [mean ± SEM]; fasting plasma glucose [FPG] 9.9 ± 0.9 mmol/L; HbA1c 6.4 ± 0.2% [47 ± 3 mmol/mol]) received 6 weeks of treatment with a GLP-1RA (liraglutide) and placebo (tablets), as well as a sulfonylurea (glimepiride) and placebo (injections), in randomized order, in a double-blind, crossover trial. Glimepiride was up-titrated once weekly in a treat-to-target manner; liraglutide was up-titrated once weekly to 1.8 mg once daily. At baseline and at the end of each treatment period a standardized liquid meal test was performed, including a 30-min light bicycle test.
  
  
  RESULTS
  FPG decreased during the treatment periods (-1.6 ± 0.5 mmol/L liraglutide [P = 0.012] and -2.8 ± 0.7 mmol/L glimepiride [P = 0.003]), with no difference between treatments (P = 0.624). Postprandial plasma glucose (PG) responses (total area under the curve) were lower with both glimepiride (2,136 ± 292 min × mmol/L) and liraglutide (2,624 ± 340 min × mmol/L) compared with baseline (3,127 ± 291 min × mmol/L; P < 0.001, glimepiride; P = 0.017, liraglutide), with no difference between treatments (P = 0.121). Eighteen episodes of hypoglycemia (PG ≤3.9 mmol/L) occurred during glimepiride treatment and one during liraglutide treatment.
  
  
  CONCLUSIONS
  Six weeks of treatment with glimepiride or liraglutide lowered FPG and postprandial glucose excursions in patients with HNF1A diabetes. The glucose-lowering effect was greater with glimepiride at the expense of a higher risk of exclusively mild hypoglycemia.
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark s.ostoft@dadlnet.dk.
authors.forename: Signe H
authors.initials: SH
authors.lastname: Østoft
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonatan I
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkFaculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, DenmarkFaculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
authors.affiliation: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkFaculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D018027:Receptors, Glucagon / Q000819:agonists; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D018027:Receptors, Glucagon; D013453:Sulfonylurea Compounds; C000593833:GLP1R protein, human; C057619:glimepiride