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.
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.
Profil Mainz, Rheinstrasse 4C, 55116, Mainz, Germany.
Thomas
T
Forst
Ernestos
E
Anastassiadis
Stephan
S
Diessel
Andrea
A
Löffler
Andreas
A
Pfützner
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D000069476:Linagliptin; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D019518:Postprandial Period / Q000502:physiology*; D011384:Proinsulin / Q000097:blood; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D011687:Purines; D011799:Quinazolines; D013453:Sulfonylurea Compounds; D000069476:Linagliptin; C057619:glimepiride; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D011384:Proinsulin; D008687:Metformin
DPP-IV; diabetes mellitus; glimepiride; islet cell function