Combination of the dipeptidyl peptidase-4 inhibitor linagliptin with insulin-based regimens in type 2 diabetes and chronic kidney disease

Diab Vasc Dis Res. 2015 Jul;12(4):249-57. doi: 10.1177/1479164115579001. Epub 2015 May 4.

Abstract

Glucose-lowering treatment options for type 2 diabetes mellitus patients with chronic kidney disease are limited. We evaluated the potential for linagliptin in combination with insulin in type 2 diabetes mellitus patients with mild-to-severe renal impairment. Data for participants in two phase 3 trials with linagliptin who were receiving insulin were analysed separately (n = 811). Placebo-adjusted mean HbA1c changes from baseline were -0.59% (mild renal impairment) and -0.69% (moderate renal impairment) after 24 weeks and -0.43% (severe renal impairment) after 12 weeks. Drug-related adverse events with linagliptin were similar to placebo (mild renal impairment: 19.9% vs. 26.5%; moderate renal impairment: 22.0% vs. 25.0%; severe renal impairment: 46.3% vs. 43.6%, respectively). Frequencies of hypoglycaemia in patients with mild, moderate and severe renal impairment were 34.9%, 35.6% and 66.7% with linagliptin and 37.5%, 39.7% and 49.1% with placebo, respectively. Episodes of severe hypoglycaemia were low (⩽5.6%). Adding linagliptin to insulin in type 2 diabetes mellitus patients with chronic kidney disease improved glucose control and was well tolerated.

Keywords: Type 2 diabetes mellitus; chronic kidney disease; dipeptidyl peptidase-4 inhibitor; linagliptin.

Publication types

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

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Nephropathies / etiology*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate
  • Glycated Hemoglobin / metabolism
  • Glycoside Hydrolase Inhibitors / therapeutic use
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Linagliptin / therapeutic use*
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Pioglitazone
  • Renal Insufficiency, Chronic / etiology*
  • Retrospective Studies
  • Severity of Illness Index
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • Linagliptin
  • Metformin
  • Pioglitazone