Kidney Week

Abstract: FR-OR142

Effect of Linagliptin on Kidney and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Kidney Disease: CARMELINA®

Session Information

• High-Impact Clinical Trials
  October 26, 2018 | Location: 20A, San Diego Convention Center
  Abstract Time: 10:30 AM - 10:45 AM

Category: Diabetic Kidney Disease

• No subcategory defined

Authors

• Perkovic, Vlado, The George Institute for Global Health , Newtown, New South Wales, Australia

Vlado Perkovic, MBBS, PhD, FASN

• Toto, Robert D., University of Texas Southwestern Medical Center, Dallas, Texas, United States

Robert D. Toto,

• Cooper, Mark E., Monash University, Melbourne, Victoria, Australia

Mark E. Cooper,

• Johansen, Odd Erik, Boehringer Ingelheim Norway, Asker, Norway

Odd Erik Johansen,

• Rosenstock, Julio, Dallas Diabetes Research Center at Medical City, Dallas, Texas, United States

Julio Rosenstock,

• Mcguire, Darren K, UT Southwestern Medical Center at Dallas, Dallas, Texas, United States

Darren K Mcguire,

• Kahn, Steven E., University of Washington, Seattle, Washington, United States

Steven E. Kahn,

• Marx, Nikolaus, University Hospital Aachen, Aachen, Germany

Nikolaus Marx,

• Alexander, John H., Duke Clinical Research Institute, Durham, North Carolina, United States

John H. Alexander,

• Zinman, Bernard, Mount Sinai Hospital, Toronto, Ontario, Canada

Bernard Zinman,

• Baanstra, David, Boehringer Ingelheim, Alkmaar, Netherlands

David Baanstra,

• Pfarr, Egon, Boehringer Ingelheim, Ingelheim, Germany

Egon Pfarr,

• Schnaidt, Sven Yannik, Boehringer Ingelheim, Ingelheim, Germany

Sven Yannik Schnaidt,

• Meinicke, Thomas, Boehringer Ingelheim International GmbH, Biberach, Germany

Thomas Meinicke,

• George, Jyothis T, Boehringer Ingelheim, Ingelheim, Germany

Jyothis T George,

• von Eynatten, Maximilian, Boehringer Ingelheim, Ingelheim, Germany

Maximilian von Eynatten,

• Wanner, Christoph, University Hospital, Wuerzburg, Germany

Christoph Wanner,

Background

Type 2 diabetes (T2D) is a common cause of ESKD so the effects of glucose-lowering therapies on kidney outcomes are of great interest, especially in people with CKD.

Methods

CARMELINA (NCT01897532) randomized people with T2D and prevalent CKD (UACR >30 mg/g with concomitant CV disease, OR eGFR 45-75 ml/min/1.73m² and UACR > 200 mg/g OR eGFR 15-45 regardless of UACR) to receive double-blind linagliptin (5 mg, a DPP inhibitor) or placebo QD. The primary CV endpoint was 3P-MACE, with a key secondary kidney endpoint (adjudicated ESKD, renal death, or sustained ≥40% decrease in eGFR from baseline). Other renal outcomes included albuminuria and eGFR slope. Subgroups were assessed by baseline eGFR (≥/<45 and ≥/< 30, 45 or 60 ml/min/1.73m²).

Results

6979 participants (mean age 66 yrs, HbA1c 8.0%, eGFR 54.6 ml/min/1.73m², 43% eGFR ≤45, and 80% UACR ≥30 mg/g) from 27 countries were followed for median 2.2 yrs. Linagliptin reduced albuminuria progression and albuminuria levels (table), but eGFR-slope was unaffected. Rates of the secondary kidney endpoint (HR 1.04 [0.89, 1.22]) and renal death, or sustained ESKD (0.87 [0.69, 1.10]), as well as 3P-MACE and hospitalization for heart failure (table) were similar between groups. Incidence rates were higher with reduced eGFR, however, results were consistent across subgroups (p heterogeneity >0.1).

Conclusion

Linagliptin slowed progression of albuminuria, without affecting eGFR slope or other kidney outcomes. Linagliptin also demonstrated CV safety including in patients with advanced CKD where clinical evidence has been particularly scarce.

Funding

• Commercial Support – Boehringer Ingelheim and the Eli Lilly diabetes alliance