title: Efficacy and Safety of Liraglutide Versus Placebo as Add-on to Glucose-Lowering Therapy in Patients With Type 2 Diabetes and Moderate Renal Impairment (LIRA-RENAL): A Randomized Clinical Trial.
abstract: OBJECTIVE
  Renal impairment in type 2 diabetes limits available glucose-lowering treatment options. This trial was conducted to establish the efficacy and safety of liraglutide as an add-on to existing glucose-lowering medications in patients with inadequately controlled type 2 diabetes and moderate renal impairment.
  
  
  METHODS
  In this 26-week, double-blind trial, 279 patients with HbA1c 7-10%, BMI 20-45 kg/m(2), and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2); MDRD) were randomized (1:1) to once-daily liraglutide 1.8 mg (n = 140) or placebo (n = 139).
  
  
  RESULTS
  The estimated treatment difference in HbA1c from baseline to week 26 was -0.66% (-7.25 mmol/mol) (95% CI -0.90 to -0.43 [-9.82 to -4.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (-1.22 mmol/L [-22.0 mg/dL]) than with placebo (-0.57 mmol/L [-10.3 mg/dL], P = 0.036). There was a greater reduction in body weight with liraglutide (-2.41 kg) than with placebo (-1.09 kg, P = 0.0052). No changes in renal function were observed (eGFR relative ratio to baseline: -1% liraglutide, +1% placebo; estimated treatment ratio [ETR] 0.98, P = 0.36). The most common adverse events were gastrointestinal (GI) adverse effects (liraglutide, 35.7%; placebo, 17.5%). No difference in hypoglycemic episodes was observed between treatment groups (event rate/100 patient-years of exposure: liraglutide, 30.47; placebo, 40.08; P = 0.54). The estimated ratio to baseline for lipase was 1.33 for liraglutide and 0.97 for placebo (ETR 1.37, P < 0.0001).
  
  
  CONCLUSIONS
  Liraglutide did not affect renal function and demonstrated better glycemic control, with no increase in hypoglycemia risk but with higher withdrawals due to GI adverse events than placebo in patients with type 2 diabetes and moderate renal impairment.
authors.affiliation: Diabetes Research Centre, University of Leicester, Leicester, U.K. melanie.davies@uhl-tr.nhs.uk.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: Institute of Life Science, Swansea University, Swansea, U.K.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bain
authors.affiliation: Qatar Foundation, Weill Cornell Medical College, Doha, Qatar.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Atkin
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: Clinical Research Development Associates, Rosedale, NY.
authors.forename: David
authors.initials: D
authors.lastname: Scott
authors.affiliation: Department of Diabetic Nephropathy, Endocrinology Research Centre, Moscow, Russia.
authors.forename: Minara S
authors.initials: MS
authors.lastname: Shamkhalova
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Bosch-Traberg
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Annika
authors.initials: A
authors.lastname: Syrén
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Emory University, Atlanta, GA.
authors.forename: Guillermo E
authors.initials: GE
authors.lastname: Umpierrez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069450:Liraglutide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000069450:Liraglutide