Linagliptin added to sulphonylurea in uncontrolled type 2 diabetes patients with moderate-to-severe renal impairment

Janet B McGill; Anthony H Barnett; Andrew J Lewin; Sanjay Patel; Dietmar Neubacher; Maximilian von Eynatten; Hans-Juergen Woerle

doi:10.1177/1479164113507068

Linagliptin added to sulphonylurea in uncontrolled type 2 diabetes patients with moderate-to-severe renal impairment

Diab Vasc Dis Res. 2014 Jan;11(1):34-40. doi: 10.1177/1479164113507068. Epub 2013 Oct 29.

Authors

Janet B McGill¹, Anthony H Barnett, Andrew J Lewin, Sanjay Patel, Dietmar Neubacher, Maximilian von Eynatten, Hans-Juergen Woerle

Affiliation

¹ Division of Endocrinology, Metabolism and Lipid Research, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.

PMID: 24169807
DOI: 10.1177/1479164113507068

Abstract

Glucose-lowering treatment options are limited for uncontrolled type 2 diabetes mellitus (T2DM) patients with advanced stages of renal impairment (RI). This retrospective analysis evaluated glycaemic efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor linagliptin added to sulphonylurea. Three randomized phase 3 studies (n = 619) including T2DM subjects with moderate or severe RI [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²] were analysed; only sulphonylurea-treated subjects who received additional linagliptin (n = 58) or placebo (n = 33) were evaluated. Linagliptin provided meaningful placebo-adjusted HbA1c reductions of -0.68% (95% confidence interval: -1.19, -0.17), -1.08% (-2.02, -0.14) and -0.62% (-1.25, 0.01) after 24, 18 and 12 weeks, respectively. There was a similar incidence of overall adverse events (linagliptin: 79.3%, placebo: 75.8%) and hypoglycaemia (linagliptin: 37.9%, placebo: 39.4%). Severe hypoglycaemia was more common with placebo (linagliptin: 1.7%, placebo: 6.1%). These data suggest that linagliptin is a safe and effective glucose-lowering treatment in T2DM patients with moderate-to-severe RI for whom sulphonylurea treatment is no longer sufficient.

Trial registration: ClinicalTrials.gov NCT00800683 NCT00819091 NCT01084005.

Keywords: Linagliptin; efficacy; renal impairment; safety; sulphonylurea; type 2 diabetes.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Diabetes Mellitus, Type 2 / blood
Diabetes Mellitus, Type 2 / complications
Diabetes Mellitus, Type 2 / drug therapy*
Diabetic Nephropathies / chemically induced
Diabetic Nephropathies / physiopathology*
Dipeptidyl-Peptidase IV Inhibitors / adverse effects
Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
Double-Blind Method
Drug Monitoring
Drug Resistance*
Drug Therapy, Combination / adverse effects
Female
Glycated Hemoglobin / analysis
Humans
Hyperglycemia / prevention & control
Hypoglycemia / chemically induced
Hypoglycemia / prevention & control
Hypoglycemic Agents / adverse effects
Hypoglycemic Agents / therapeutic use*
Kidney / drug effects
Kidney / physiopathology
Linagliptin
Male
Middle Aged
Purines / adverse effects
Purines / therapeutic use*
Quinazolines / adverse effects
Quinazolines / therapeutic use*
Renal Insufficiency, Chronic / chemically induced
Renal Insufficiency, Chronic / complications
Renal Insufficiency, Chronic / physiopathology
Retrospective Studies
Severity of Illness Index
Sulfonylurea Compounds / adverse effects
Sulfonylurea Compounds / therapeutic use*

Substances

Dipeptidyl-Peptidase IV Inhibitors
Glycated Hemoglobin A
Hypoglycemic Agents
Purines
Quinazolines
Sulfonylurea Compounds
hemoglobin A1c protein, human
Linagliptin

Associated data

ClinicalTrials.gov/NCT00800683
ClinicalTrials.gov/NCT00819091
ClinicalTrials.gov/NCT01084005