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 - TY - JOUR A1 - Groop, Per-Henrik A1 - Cooper, Mark E. A1 - Perkovic, Vlado A1 - Sharma, Kumar A1 - Schernthaner, Guntram A1 - Haneda, Masakazu A1 - Hocher, Berthold A1 - Gordat, Maud A1 - Cescutti, Jessica A1 - Woerle, Hans-Juergen A1 - von Eynatten, Maximilian T1 - Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2D trial JF - Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease N2 - Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5mg or placebo in addition to their stable glucose-lowering background therapy for 24weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24weeks with =0.05. MARLINA-T2D is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease. KW - Dipeptidyl peptidase-4 inhibition KW - linagliptin KW - type 2 diabetes KW - chronic kidney disease KW - glycaemic control KW - albuminuria Y1 - 2015 U6 - https://doi.org/10.1177/1479164115579002 SN - 1479-1641 SN - 1752-8984 VL - 12 IS - 6 SP - 455 EP - 462 PB - Sage Publ. CY - London ER - TY - GEN A1 - Groop, Per-Henrik A1 - Cooper, Mark E. A1 - Perkovic, Vlado A1 - Sharma, Kumar A1 - Schernthaner, Guntram A1 - Haneda, Masakazu A1 - Hocher, Berthold A1 - Gordat, Maud A1 - Cescutti, Jessica A1 - Woerle, Hans-Juergen A1 - von Eynatten, Maximilian T1 - Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction BT - Rationale and design of the MARLINA–T2D TM trial T2 - Diabetes & vascular disease research N2 - Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5mg or placebo in addition to their stable glucose-lowering background therapy for 24weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24weeks with =0.05. MARLINA-T2D is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 419 KW - Dipeptidyl peptidase-4 inhibition KW - linagliptin KW - type 2 diabetes KW - chronic kidney disease KW - glycaemic control KW - albuminuria Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-404460 ER -