title: Safety and Efficacy of Incretin-Based Therapies in Patients With Type 2 Diabetes Mellitus and CKD: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  The pharmacokinetics and pharmacodynamics of antidiabetic therapies for patients with type 2 diabetes are often altered in the context of chronic kidney disease (CKD).
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Patients with type 2 diabetes and CKD.
  
  
  METHODS
  2 reviewers independently screened studies identified through bibliographic databases (Cochrane Library, PubMed, Embase, International Pharmaceutical Abstracts), clinical trial registries, and references from pertinent articles and clinical practice guidelines. Eligible studies included randomized controlled trials evaluating incretin-based therapy in adults with type 2 diabetes and estimated glomerular filtration rates < 60mL/min/1.73m2.
  
  
  METHODS
  Incretin-based therapies (dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists) compared to placebo or active antidiabetic therapies.
  
  
  RESULTS
  Changes in glycated hemoglobin (HbA1c), hypoglycemia, mortality, change in fasting plasma glucose, cardiovascular events, and end-stage renal disease.
  
  
  RESULTS
  Of 1,619 nonduplicate records screened, 13 studies were included. Compared to placebo, incretin-based therapies significantly reduced HbA1clevels (n = 9; weighted mean difference, -0.64; 95% CI, -0.79 to -0.48; I2= 43%); however, compared with active comparators, they did not (n = 4; weighted mean difference, -0.07; 95% CI, -0.25 to 0.12; I2= 38%). Incretin-based therapies significantly increased the risk for hypoglycemia compared to placebo (n = 7; relative risk [RR], 1.38; 95% CI, 1.01-1.89; I2= 0%) but no effect was observed versus active comparators (n = 4; RR, 0.24; 95% CI, 0.03-1.94; I2= 52%). Limited evidence exists for all-cause mortality (placebo: n = 7 [RR, 1.21; 95% CI, 0.64-2.29; I2= 0%]; active comparators: n = 3 [RR, 0.70; 95% CI, 0.32-1.54; I2= 0%]).
  
  
  CONCLUSIONS
  Variation among interventions, small number of studies, heterogeneity between studies, and high risk for attrition bias in 7 of the selected studies.
  
  
  CONCLUSIONS
  In patients with moderate or severe CKD, incretin-based therapies are effective in reducing HbA1clevels. Hypoglycemic events are rare, and wide CIs for the association preclude any definitive conclusions. Likewise, wide CIs were observed for mortality, cardiovascular events, and end-stage renal disease.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Howse
authors.affiliation: School of Pharmacy, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Lyudmila N
authors.initials: LN
authors.lastname: Chibrikova
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada; School of Pharmacy, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: Twells
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Barrett
authors.affiliation: School of Pharmacy, Memorial University of Newfoundland, St. John's, Canada. Electronic address: jgamble@mun.ca.
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Gamble
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D006801:Humans; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D016896:Treatment Outcome
chemical_list: D054795:Incretins
keywords: Type 2 diabetes mellitus (T2DM); antidiabetic therapies; chronic kidney disease (CKD); dipeptidyl peptidase 4 inhibitor (DPP-4); efficacy; epidemiology; glucagon-like peptide 1 (GLP-1) receptor agonist; glycated hemoglobin (HbA(1c)); hyperglycemia; incretin; meta-analysis; pharmacoepidemiology; safety; systematic review