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
- Janet B. McGill, MD1⇓,
- Lance Sloan, MD2,
- Jennifer Newman, BS3,
- Sanjay Patel, MB, CHB4,
- Christophe Sauce, MS5,
- Maximilian von Eynatten, MD6 and
- Hans-Juergen Woerle, MD6
- 1Division of Endocrinology, Metabolism and Lipid Research, Washington University in St. Louis, St. Louis, Missouri
- 2Texas Institute for Kidney and Endocrine Disorders, Lufkin, Texas
- 3Boehringer Ingelheim, Ridgefield, Connecticut
- 4Boehringer Ingelheim, Bracknell, U.K.
- 5Boehringer Ingelheim, Reims, France
- 6Boehringer Ingelheim, Ingelheim, Germany
- Corresponding author: Janet B. McGill, .
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.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc12-0706/-/DC1.
A slide set summarizing this article is available online.
A complete list of the study investigators can be found in the Supplementary Data online.
- Received April 13, 2012.
- Accepted July 21, 2012.
- © 2013 by the American Diabetes Association.
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