Long-Term Efficacy and Safety of Linagliptin in Patients With Type 2 Diabetes and Severe Renal Impairment

A 1-year, randomized, double-blind, placebo-controlled study

  1. Hans-Juergen Woerle, MD6
  1. 1Division of Endocrinology, Metabolism and Lipid Research, Washington University in St. Louis, St. Louis, Missouri
  2. 2Texas Institute for Kidney and Endocrine Disorders, Lufkin, Texas
  3. 3Boehringer Ingelheim, Ridgefield, Connecticut
  4. 4Boehringer Ingelheim, Bracknell, U.K.
  5. 5Boehringer Ingelheim, Reims, France
  6. 6Boehringer Ingelheim, Ingelheim, Germany
  1. Corresponding author: Janet B. McGill, jmcgill{at}


OBJECTIVE This placebo-controlled study assessed long-term efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment (RI).

RESEARCH DESIGN AND METHODS In this 1-year, double-blind study, 133 patients with type 2 diabetes (HbA1c 7.0–10.0%) and severe RI (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) at screening were randomized to linagliptin 5 mg (n = 68) or placebo (n = 65) once daily, added to existing background therapy. The primary efficacy end point was HbA1c change from baseline to week 12. Efficacy and safety end points were assessed after 1 year.

RESULTS At week 12, adjusted mean HbA1c decreased by −0.76% with linagliptin and −0.15% with placebo (treatment difference, −0.60%; 95% CI −0.89 to −0.31; P < 0.0001). HbA1c improvements were sustained with linagliptin (−0.71%) over placebo (0.01%) at 1 year (treatment difference −0.72%, −1.03 to −0.41; P < 0.0001). Mean insulin doses decreased by −6.2 units with linagliptin and −0.3 units with placebo. Overall adverse event incidence was similar over 1 year (94.1 vs. 92.3%). Incidence of severe hypoglycemia with linagliptin and placebo was comparably low (three patients per group). Linagliptin and placebo had little effect on renal function (median change in eGFR, −0.8 vs. −2.2 mL/min/1.73 m2), and no drug-related renal failure occurred.

CONCLUSIONS In patients with type 2 diabetes and severe RI, linagliptin provided clinically meaningful improvements in glycemic control with very low risk of severe hypoglycemia, stable body weight, and no cases of drug-related renal failure. The potential for linagliptin to spare insulin and provide long-term renal safety warrants further investigations.


  • Received April 13, 2012.
  • Accepted July 21, 2012.

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