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Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA ‐ T2D trial
Author(s) -
Groop PerHenrik,
Cooper Mark E.,
Perkovic Vlado,
Hocher Berthold,
Kanasaki Keizo,
Haneda Masakazu,
Schernthaner Guntram,
Sharma Kumar,
Stanton Robert C.,
Toto Robert,
Cescutti Jessica,
Gordat Maud,
Meinicke Thomas,
KoitkaWeber Audrey,
Thiemann Sandra,
von Eynatten Maximilian
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13041
Subject(s) - linagliptin , albuminuria , medicine , urology , type 2 diabetes , placebo , renal function , microalbuminuria , creatinine , clinical endpoint , diabetes mellitus , confidence interval , endocrinology , randomized controlled trial , gastroenterology , alternative medicine , pathology
Aims The MARLINA ‐ T2D study ( ClinicalTrials.gov , NCT 01792518) 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‐to‐creatinine 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.