title: Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.
abstract: OBJECTIVE
  To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO.
  
  
  METHODS
  Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.
  
  
  RESULTS
  41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings.
  
  
  CONCLUSIONS
  NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Freemantle
authors.affiliation: Global Evidence & Value Development/Health Economics & Outcomes Research, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Engels
authors.initials: E
authors.lastname: Chou
authors.affiliation: Analysis Group, AG, Boston, Massachusetts, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Frois
authors.affiliation: Analysis Group, AG, Boston, Massachusetts, USA.
authors.forename: Daisy
authors.initials: D
authors.lastname: Zhuo
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Lehmacher
authors.affiliation: Global Medical Affairs Diabetes, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Vlajnic
authors.affiliation: Global Evidence & Value Development/Health Economics & Outcomes Research, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: TechData Service Company, LLC, King of Prussia, Pennsylvania, USA.
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Chung
authors.affiliation: Global Evidence & Value Development/Health Economics & Outcomes Research, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Quanwu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Analysis Group, AG, Boston, Massachusetts, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Wu
authors.affiliation: Global Evidence & Value Development/Health Economics & Outcomes Research, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Gerrits
mesh_terms: D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine
keywords: DIABETES & ENDOCRINOLOGY