Effect of linagliptin compared with glimepiride on postprandial glucose metabolism, islet cell function and vascular function parameters in patients with type 2 diabetes mellitus receiving ongoing metformin treatment

Diabetes Metab Res Rev. 2014 Oct;30(7):582-9. doi: 10.1002/dmrr.2525.

Abstract

Background: The goal of this study was to investigate the effects of linagliptin compared with glimepiride on alpha and beta cell function and several vascular biomarkers after a standardized test meal.

Methods: Thirty-nine patients on metformin alone (age, 64 ± 7 years; duration of type 2 diabetes mellitus, 7.8 ± 4.5years, 27 male, 12 female; HbA1c , 57.2 ± 6.9 mmol/mol; mean ± SD) were randomized to receive linagliptin 5 mg (n = 19) or glimepiride (n = 20) for a study duration of 12 weeks. Glucagon-like peptide 1, blood glucose, insulin, intact proinsulin, glucagon, plasminogen activator inhibitor-1 (PAI-1), cyclic guanosinmonophosphat and asymetric dimethylarginin levels were measured in the fasting state and postprandial at 30-min intervals for a duration of 5 h. The areas under the curve (AUC0-300 min ) were calculated for group comparisons.

Results: HbA1c , fasting and postprandial glucose levels improved in both groups. An increase in postprandial insulin (22595 ± 5984 pmol/L*min), postprandial intact proinsulin (1359 ± 658 pmol/L*min), postprandial glucagon (317 ± 1136 pg/mL*min) and postprandial PAI-1 levels (863 ± 467 ng/mL*min) could be observed during treatment with glimepiride, whereas treatment with linagliptin was associated with a decrease in postprandial insulin (-8007 ± 4204 pmol/L*min), intact proinsulin (-1771 ± 426 pmol/L*min), postprandial glucagon (-1597 ± 1831 pg/mL*min) and PAI-1 levels (-410 ± 276 ng/mL*min).

Conclusions: Despite an improvement in blood glucose control in both groups, linagliptin reduced postprandial insulin, proinsulin, glucagon and PAI-levels. These results indicate an improvement in postprandial alpha and beta cell function, as well as a reduced postprandial vascular risk profile during treatment with linagliptin.

Keywords: DPP-IV; diabetes mellitus; glimepiride; islet cell function.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Therapy, Combination
  • Female
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Linagliptin
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood
  • Postprandial Period / physiology*
  • Proinsulin / blood
  • Purines / pharmacology
  • Purines / therapeutic use*
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Risk Factors
  • Sulfonylurea Compounds / pharmacology
  • Sulfonylurea Compounds / therapeutic use*

Substances

  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Plasminogen Activator Inhibitor 1
  • Purines
  • Quinazolines
  • Sulfonylurea Compounds
  • Linagliptin
  • glimepiride
  • Glucagon-Like Peptide 1
  • Glucagon
  • Proinsulin
  • Metformin