Effects of lixisenatide on elevated liver transaminases: systematic review with individual patient data meta-analysis of randomised controlled trials on patients with type 2 diabetes

TY - JOUR

T1 - Effects of lixisenatide on elevated liver transaminases

T2 - systematic review with individual patient data meta-analysis of randomised controlled trials on patients with type 2 diabetes

AU - Gluud, Lise L

AU - Knop, Filip K

AU - Vilsbøll, Tina

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PY - 2014

Y1 - 2014

N2 - OBJECTIVE: To evaluate the effects of the glucagon-like peptide-1 receptor agonist lixisenatide on elevated liver blood tests in patients with type 2 diabetes.DESIGN: Systematic review.DATA SOURCES: Electronic and manual searches were combined.STUDY SELECTION: Randomised controlled trials (RCTs) on lixisenatide versus placebo or active comparators for type 2 diabetes were included.PARTICIPANTS: Individual patient data were retrieved to calculate outcomes for patients with elevated liver blood tests.MAIN OUTCOME MEASURES: Normalisation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).DATA SYNTHESIS: The results of included trials were combined in meta-analyses. Sequential, subgroup and regression analyses were performed to evaluate heterogeneity and bias.RESULTS: We included 12 RCTs on lixisenatide versus placebo and 3 RCTs with the active comparators liraglutide, exenatide or sitagliptin. The mean treatment duration was 29 weeks. Lixisenatide increased the proportion of patients with normalisation of ALT (risk difference: 0.07; 95% CI 0.01 to 0.14; number needed to treat: 14 patients, p=0.042). The effect was not confirmed in sequential analysis. No effects of lixisenatide were identified on AST, alkaline phosphatase or bilirubin. No evidence of bias was identified. Mixed effect multilevel meta-regression analyses suggest that the benefit of lixisenatide on ALT was limited to patients who were overweight or obese.CONCLUSIONS: This review suggests that lixisenatide increases the proportion of obese or overweight patients with type 2 diabetes who achieve normalisation of ALT. Additional research is needed to determine if the findings translate to clinical outcome measures.TRIAL REGISTRATION NUMBER: PROSPERO; CRD42013005779.

AB - OBJECTIVE: To evaluate the effects of the glucagon-like peptide-1 receptor agonist lixisenatide on elevated liver blood tests in patients with type 2 diabetes.DESIGN: Systematic review.DATA SOURCES: Electronic and manual searches were combined.STUDY SELECTION: Randomised controlled trials (RCTs) on lixisenatide versus placebo or active comparators for type 2 diabetes were included.PARTICIPANTS: Individual patient data were retrieved to calculate outcomes for patients with elevated liver blood tests.MAIN OUTCOME MEASURES: Normalisation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).DATA SYNTHESIS: The results of included trials were combined in meta-analyses. Sequential, subgroup and regression analyses were performed to evaluate heterogeneity and bias.RESULTS: We included 12 RCTs on lixisenatide versus placebo and 3 RCTs with the active comparators liraglutide, exenatide or sitagliptin. The mean treatment duration was 29 weeks. Lixisenatide increased the proportion of patients with normalisation of ALT (risk difference: 0.07; 95% CI 0.01 to 0.14; number needed to treat: 14 patients, p=0.042). The effect was not confirmed in sequential analysis. No effects of lixisenatide were identified on AST, alkaline phosphatase or bilirubin. No evidence of bias was identified. Mixed effect multilevel meta-regression analyses suggest that the benefit of lixisenatide on ALT was limited to patients who were overweight or obese.CONCLUSIONS: This review suggests that lixisenatide increases the proportion of obese or overweight patients with type 2 diabetes who achieve normalisation of ALT. Additional research is needed to determine if the findings translate to clinical outcome measures.TRIAL REGISTRATION NUMBER: PROSPERO; CRD42013005779.

U2 - 10.1136/bmjopen-2014-005325

DO - 10.1136/bmjopen-2014-005325

M3 - Review

C2 - 25526792

SN - 2044-6055

VL - 4

SP - 1

EP - 10

JO - BMJ Open

JF - BMJ Open

IS - 12

M1 - e005325

ER -