TY  - JOUR
A1  - Groop, Per-Henrik
A1  - Cooper, Mark E.
A1  - Perkovic, Vlado
A1  - Hocher, Berthold
A1  - Kanasaki, Keizo
A1  - Haneda, Masakazu
A1  - Schernthaner, Guntram
A1  - Sharma, Kumar
A1  - Stanton, Robert C.
A1  - Toto, Robert
A1  - Cescutti, Jessica
A1  - Gordat, Maud
A1  - Meinicke, Thomas
A1  - Koitka-Weber, Audrey
A1  - Thiemann, Sandra
A1  - von Eynatten, Maximilian
T1  - Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction
BT  - the randomized MARLINA-T2D trial
JF  - Diabetes obesity & metabolism : a journal of pharmacology and therapeutics
N2  - Aims: The MARLINA-T2D study (ClinicalTrials. gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods: A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/ mol), estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m(2) and urinary albumin-tocreatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8% +/- 0.9% (62.2 +/- 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6 mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7 mmol/mol]; P <.0001). The placebo-adjusted gMean for time-weighted average of percentage change in UACR from baseline was -6.0% (95% CI, -15.0 to 3.0; P =.1954). The adverse-event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups. Conclusions: In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.
KW  - antidiabetic drug
KW  - clinical trial
KW  - diabetic nephropathy
KW  - DPP-IV inhibitor
KW  - glycaemic control
KW  - linagliptin
Y1  - 2017
U6  - https://doi.org/10.1111/dom.13041
SN  - 1462-8902
SN  - 1463-1326
VL  - 19
IS  - 11
SP  - 1610
EP  - 1619
PB  - Wiley
CY  - Hoboken
ER  -