Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: The randomized MARLINA-T2D trial

Per Henrik Groop, Mark E. Cooper, Vlado Perkovic, Berthold Hocher, Keizo Kanasaki, Masakazu Haneda, Guntram Schernthaner, Kumar Sharma, Robert C. Stanton, Robert Toto, Jessica Cescutti, Maud Gordat, Thomas Meinicke, Audrey Koitka-Weber, Sandra Thiemann, Maximilian von Eynatten

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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% (48-86mmol/mol), estimated glomerular filtration rate (eGFR)≥30mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 30-3000mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n=182) or placebo (n=178) for 24weeks. 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 24weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8%±0.9% (62.2±9.6mmol/mol) and 126mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7mmol/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.

Original languageEnglish (US)
JournalDiabetes, Obesity and Metabolism
DOIs
StateAccepted/In press - 2017

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Albuminuria
Hyperglycemia
Type 2 Diabetes Mellitus
Placebos
Albumins
Creatinine
Kidney
Glomerular Filtration Rate
Confidence Intervals
Diabetic Nephropathies
Standard of Care
Renin-Angiotensin System
Fibrosis
Hemodynamics
Linagliptin
Safety

Keywords

  • Antidiabetic drug
  • Clinical trial
  • Diabetic nephropathy
  • DPP-IV inhibitor
  • Glycaemic control
  • Linagliptin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction : The randomized MARLINA-T2D trial. / Groop, Per Henrik; 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; Koitka-Weber, Audrey; Thiemann, Sandra; von Eynatten, Maximilian.

In: Diabetes, Obesity and Metabolism, 2017.

Research output: Contribution to journalArticle

Groop, PH, Cooper, ME, Perkovic, V, Hocher, B, Kanasaki, K, Haneda, M, Schernthaner, G, Sharma, K, Stanton, RC, Toto, R, Cescutti, J, Gordat, M, Meinicke, T, Koitka-Weber, A, Thiemann, S & von Eynatten, M 2017, 'Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: The randomized MARLINA-T2D trial', Diabetes, Obesity and Metabolism. https://doi.org/10.1111/dom.13041
Groop, Per Henrik ; 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 ; Koitka-Weber, Audrey ; Thiemann, Sandra ; von Eynatten, Maximilian. / Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction : The randomized MARLINA-T2D trial. In: Diabetes, Obesity and Metabolism. 2017.
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abstract = "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{\%} (48-86mmol/mol), estimated glomerular filtration rate (eGFR)≥30mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 30-3000mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n=182) or placebo (n=178) for 24weeks. 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 24weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8{\%}±0.9{\%} (62.2±9.6mmol/mol) and 126mg/g, respectively; 73.7{\%} and 20.3{\%} of participants had microalbuminuria or macroalbuminuria, respectively. After 24weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60{\%} (-6.6mmol/mol) (95{\%} confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7mmol/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.",
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T1 - Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction

T2 - The randomized MARLINA-T2D trial

AU - Groop, Per Henrik

AU - Cooper, Mark E.

AU - Perkovic, Vlado

AU - Hocher, Berthold

AU - Kanasaki, Keizo

AU - Haneda, Masakazu

AU - Schernthaner, Guntram

AU - Sharma, Kumar

AU - Stanton, Robert C.

AU - Toto, Robert

AU - Cescutti, Jessica

AU - Gordat, Maud

AU - Meinicke, Thomas

AU - Koitka-Weber, Audrey

AU - Thiemann, Sandra

AU - von Eynatten, Maximilian

PY - 2017

Y1 - 2017

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% (48-86mmol/mol), estimated glomerular filtration rate (eGFR)≥30mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 30-3000mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n=182) or placebo (n=178) for 24weeks. 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 24weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8%±0.9% (62.2±9.6mmol/mol) and 126mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7mmol/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.

AB - 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% (48-86mmol/mol), estimated glomerular filtration rate (eGFR)≥30mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 30-3000mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n=182) or placebo (n=178) for 24weeks. 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 24weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8%±0.9% (62.2±9.6mmol/mol) and 126mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7mmol/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

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