Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Effects of linagliptin on glycemic control and albuminuria in type 2 diabetes - the MARLINA–T2D™ trial (#62)

Per-Henrik Groop 1 2 , Mark E Cooper 2 , Vlado Perkovic 3 , Berthold Hocher 4 , Keizo Kanasaki 5 , Guntram Schernthaner 6 , Kumar Sharma 7 , Robert C Stanton 8 , Robert Toto 9 , Jessica Cescutti 10 , Maud Gordat 10 , Thomas Meinicke 11 , Audrey Koitka-Weber 11 , Hans-Juergen Woerle 12 , Maximilian von Eynatten 12
  1. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
  2. Baker IDI Heart & Diabetes Institute, Melbourne, VIC, Australia
  3. The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia
  4. Institute of Nutritional Science, University of Potsdam, Postdam, Germany
  5. Kanazawa Medical University, Ishikawa, Japan
  6. Department of Internal Medicine, Rudolfstiftung Hospital, Vienna, Austria
  7. Center for Renal Translational Medicine, Department of Medicine, University of California, , San Diego, La Jolla, CA, USA
  8. Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
  9. UT Southwestern Medical Center, Dallas, TX, USA
  10. Boehringer Ingelheim, Reims, France
  11. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
  12. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Introduction: Previous evidence suggests that the dipeptidyl peptidase-4 inhibitor linagliptin may exert anti-albuminuric effects beyond glycaemic control.

Objective: MARLINA–T2D™ (NCT01792518), a multicenter, double-blind, placebo -controlled clinical trial, investigated glycemic and renal effects of the DPP-4 inhibitor linagliptin (LINA) in patients with type 2 diabetes, albuminuria and eGFR ≥30 mL/min/1.73m2.

Methods: In total 360 patients with type 2 diabetes (HbA1c 6.5-10%) and persistent albuminuria (urinary albumin-to-creatinine-ratio [UACR] 30–3000 mg/gCr) despite stable background of single renin-angiotensin system blockade were randomized to LINA (n=182) or placebo (n=178) for 24 weeks. Primary glycemic and key secondary renal surrogate endpoints were HbA1c and UACR change from baseline over 24 weeks, respectively.

Results: Overall mean baseline (SD) HbA1c and geometric mean (gMean) UACR were 7.8 (0.9) % and 126 mg/gCr (microalbuminuria 73.7%; macroalbuminuria 20.3%), respectively. At week 24, placebo-adjusted mean HbA1c change from baseline was -0.60% (95% CI -0.78, -0.43; p<0.0001; Fig 1A). Placebo-adjusted gMean for time weighted average of % change from baseline in UACR over 24 weeks was -6.0% (95% CI -15.0, 3.0; NS; Fig 1B). LINA was well tolerated with a renal safety profile consistent with previous clinical trials.

Conclusion: LINA significantly improved glycemic control without a significant effect on UACR. Whether a renoprotective effect of LINA could emerge from chronic intervention in more advanced diabetic kidney disease is currently being explored in the ongoing CARMELINA™ trial.