title: Counterregulatory responses to hypoglycemia differ between glimepiride and glyburide in non diabetic individuals.
abstract: OBJECTIVE
  Reported rates of hypoglycemia in patients with type 2 diabetes mellitus are lower with glimepiride as compared to glyburide. The aim of this study was to determine whether physiologic differences in counterregulatory neuroendocrine and metabolic mechanisms during hypoglycemia provide a basis for the observed clinical differences between glimepiride and glyburide.
  
  
  METHODS
  Non-diabetic volunteers (age 38±2years, BMI 26±1kg/m(2)) were studied in a single-blind fashion during separate 2day randomized protocols consisting of 2h hyperinsulinemic (9pmol/kg/min) euglycemic (4.9±0.1mmol) and hypoglycemic (2.9±0.1mmol/L) clamps. Individuals received biologically equivalent doses of glimepiride (4mg) or glyburide (10mg) 1h prior to each glucose clamp (n=11) as well as a control group of placebo studies. Glucose kinetics were calculated using D-Glucose-6-6d2.
  
  
  RESULTS
  Insulin and C-peptide levels were increased (p<0.05) during euglycemia in both sulfonylurea groups as compared to placebo. However, despite equivalent hypoglycemia, insulin and C-peptide levels were higher (p<0.05) only after glyburide. Glucagon responses and endogenous glucose production (EGP) were decreased (p<0.05) during hypoglycemia following glyburide administration as compared to glimepiride. Glyburide reduced (p<0.05) norepinephrine responses during euglycemic clamps. In addition combined epinephrine and norepinephrine responses during hypoglycemia were reduced (p<0.05) following glyburide as compared to placebo. Leptin levels fell by a greater amount (p<0.05) during hypoglycemia with both sulfonylureas as compared to placebo.
  
  
  CONCLUSIONS
  In summary, glimepiride and glyburide can both similarly increase insulin and C-peptide levels during hyperinsulinemic euglycemia. However, during moderate hyperinsulinemic hypoglycemia (2.9mmol/L) glyburide resulted in increased C-peptide and insulin, but blunted glucagon, sympathetic nervous system and EGP responses. We conclude that glyburide can acutely reduce key neuroendocrine and metabolic counterregulatory defenses during hypoglycemia in healthy individuals.
authors.affiliation: University of Maryland, Baltimore, Department of Medicine.
authors.forename: Nino G
authors.initials: NG
authors.lastname: Joy
authors.affiliation: University of Maryland, Baltimore, Department of Medicine.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Tate
authors.affiliation: University of Maryland, Baltimore, Department of Medicine. Electronic address: sdavis@medicine.umaryland.edu.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Davis
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D010191:Pancreatic Polypeptide / Q000378:metabolism; D016037:Single-Blind Method; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D013453:Sulfonylurea Compounds; D010191:Pancreatic Polypeptide; C057619:glimepiride; D005934:Glucagon; D005905:Glyburide
keywords: Glimepiride; Glucagon; Glyburide; Hypoglycemia; Neuroendocrine counterregulation