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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.

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% (48-86?mmol/mol), estimated glomerular filtration rate (eGFR)??30?mL/min/1.73?m2 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?

SUBMITTER: Groop PH

PROVIDER: S-EPMC5655723 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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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.

Groop Per-Henrik PH Cooper Mark E ME Perkovic Vlado V Hocher Berthold B Kanasaki Keizo K Haneda Masakazu M Schernthaner Guntram G Sharma Kumar K Stanton Robert C RC Toto Robert R Cescutti Jessica J Gordat Maud M Meinicke Thomas T Koitka-Weber Audrey A Thiemann Sandra S von Eynatten Maximilian M

Diabetes, obesity & metabolism 20170731 11

<h4>Aims</h4>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.<h4>Methods</h4>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<sup>2</sup> and urinary albumin-to-creatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-sy ...[more]

PMID: 28636754

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Project description:INTRODUCTION:International clinical trials have shown that linagliptin significantly improves glycemic control and can be used at a single dose regardless of renal function in patients with type 2 diabetes (T2D). However, to date, no studies have evaluated the use of linagliptin in Japanese patients with T2D by renal function in routine clinical care. METHODS:This was a subgroup analysis of data from a prospective observational post-marketing surveillance (PMS) study of linagliptin conducted in Japan that evaluated the safety and effectiveness of linagliptin in routine clinical care for 3 years in Japanese patients with T2D. The subgroup analysis examined the patient population of this PMS study according to renal function using estimated glomerular filtration rate (eGFR) data. The incidence of linagliptin-related adverse events (adverse drug reactions [ADRs]) was the primary endpoint, and the change in glycated hemoglobin (HbA1c) from baseline to last observation was the secondary endpoint. RESULTS:Of the 2235 patients included in the safety analysis, eGFR was ≥ 90 mL/min/1.73 m2 (defined as group G1) in 16.9% (n = 377), ≥ 60 to < 90 mL/min/1.73 m2 (group G2) in 44.5% (n = 995), ≥ 30 to < 60 mL/min/1.73 m2 (group G3) in 21.7% (n = 486), ≥ 15 to < 30 mL/min/1.73 m2 (group G4) in 2.6% (n = 58) and < 15 mL/min/1.73 m2 (group G5) in 1.7% (n = 37). No eGFR data were available for 12.6% (n = 282) of patients. In these GFR groups, the incidence of ADRs with linagliptin was 6.9% in group G1, 11.1% in group G2, 13.8% in group G3, 15.5% in group G4 and 16.2% in group G5; the change in HbA1c from baseline to the last observation was - 1.11, - 0.64, - 0.35, - 0.46 and - 0.54% in the respective subgroups. CONCLUSIONS:Long-term linagliptin use showed sustained improvements in glycemic control with no new safety concerns regardless of renal function. TRIAL REGISTRATION:ClinicalTrials.gov (NCT01650259). FUNDING:This study was funded by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly Japan K.K.

Project description:ImportanceType 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease.ObjectiveTo evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events.Design, setting, and participantsRandomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A1c of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] >200 mg/g), and high renal risk (reduced eGFR and micro- or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018.InterventionsPatients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines.Main outcomes and measuresPrimary outcome was time to first occurrence of the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline.ResultsOf 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73 m2; 80.1% with UACR >30 mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI, -0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P < .001 for noninferiority). The kidney outcome occurred in 327 of 3494 (9.4%) and 306 of 3485 (8.8%), respectively (absolute incidence rate difference, 0.22 [95% CI, -0.52 to 0.97] per 100 person-years) (HR, 1.04; 95% CI, 0.89-1.22; P = .62). Adverse events occurred in 2697 (77.2%) and 2723 (78.1%) patients in the linagliptin and placebo groups; 1036 (29.7%) and 1024 (29.4%) had 1 or more episodes of hypoglycemia; and there were 9 (0.3%) vs 5 (0.1%) events of adjudication-confirmed acute pancreatitis.Conclusions and relevanceAmong adults with type 2 diabetes and high CV and renal risk, linagliptin added to usual care compared with placebo added to usual care resulted in a noninferior risk of a composite CV outcome over a median 2.2 years.Trial registrationClinicalTrials.gov Identifier: NCT01897532.

Dataset Information

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

Publications

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

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