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, Sanjib 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 journalArticleResearchpeer-review

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
Pages (from-to)1610-1619
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2017
Externally publishedYes

Keywords

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

Cite this

Groop, Per-Henrik ; Cooper, Mark E. ; Perkovic, Vlado ; Hocher, Berthold ; Kanasaki, Keizo ; Haneda, Masakazu ; Schernthaner, Guntram ; Sharma, Sanjib Kumar ; Stanton, Robert C. ; Toto, Robert ; Cescutti, Jessica ; Gordat, Maud ; Meinicke, Thomas ; Koitka-Weber, Audrey ; Thiemann, Sandra ; Eynatten, Maximilian Von. / 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 ; Vol. 19, No. 11. pp. 1610-1619.
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title = "Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: The randomized MARLINA-T2D trial",
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.",
keywords = "Antidiabetic drug, Clinical trial, Diabetic nephropathy, DPP-IV inhibitor, Glycaemic control, Linagliptin",
author = "Per-Henrik Groop and Cooper, {Mark E.} and Vlado Perkovic and Berthold Hocher and Keizo Kanasaki and Masakazu Haneda and Guntram Schernthaner and Sharma, {Sanjib Kumar} and Stanton, {Robert C.} and Robert Toto and Jessica Cescutti and Maud Gordat and Thomas Meinicke and Audrey Koitka-Weber and Sandra Thiemann and Eynatten, {Maximilian Von}",
year = "2017",
month = "11",
doi = "10.1111/dom.13041",
language = "English",
volume = "19",
pages = "1610--1619",
journal = "Diabetes, Obesity and Metabolism",
issn = "1463-1326",
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number = "11",

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Groop, P-H, Cooper, ME, Perkovic, V, Hocher, B, Kanasaki, K, Haneda, M, Schernthaner, G, Sharma, SK, Stanton, RC, Toto, R, Cescutti, J, Gordat, M, Meinicke, T, Koitka-Weber, A, Thiemann, S & Eynatten, MV 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, vol. 19, no. 11, pp. 1610-1619. https://doi.org/10.1111/dom.13041

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, Sanjib Kumar; Stanton, Robert C.; Toto, Robert; Cescutti, Jessica; Gordat, Maud; Meinicke, Thomas; Koitka-Weber, Audrey; Thiemann, Sandra; Eynatten, Maximilian Von.

In: Diabetes, Obesity and Metabolism, Vol. 19, No. 11, 11.2017, p. 1610-1619.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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, Sanjib 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 - Eynatten, Maximilian Von

PY - 2017/11

Y1 - 2017/11

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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SN - 1463-1326

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