title: Insulin glargine in a Brazilian state: should the government disinvest? An assessment based on a systematic review.
abstract: OBJECTIVE
  The costs of the insulin analogue (insulin glargine) have been growing appreciably in the State of Minas Gerais in Brazil, averaging 291% per year in recent years. This growth has been driven by an increasing number of successful law suits and a 536% price difference between insulin glargine and neutral protamine Hagedorn (NPH) insulin. One potential way to address this is to undertake a systematic review assessing the efficacy and safety of insulin glargine analogue compared with NPH insulin in patients with type 1 diabetes mellitus (T1DM), and, as a result, provide published data to support future recommended activities by the State of Minas Gerais. These could include maintaining it on the list of the Public Health System (SUS) provided there is a price reduction. Alternatively, the review could provide potential arguments to defend against future law suits should the authorities decide to delist insulin glargine.
  
  
  METHODS
  A systematic review of published studies researching the effectiveness of insulin glargine in patients with T1DM between January 1970 and July 2009 in MEDLINE (PubMed), the Latin American and Caribbean Centre on Health Sciences Information, the Cochrane Controlled Trials Databases and the National Health Service Centre for Reviews and Dissemination. Inclusion criteria included insulin glargine on its own or combined with other insulin formulations. Only randomised controlled clinical trials were included. Initially, the titles of all studies were assessed by two independent reviewers before being potentially discarded, with the quality of papers assessed using a modified Jadad scale. The outcome measures included blood levels of glycated haemoglobin, episodes of hypoglycaemia, adverse effects and the reduction of microvascular and macrovascular end-organ complications of T1DM.
  
  
  RESULTS
  Out of 803 studies found in the selected databases, only eight trials met the inclusion criteria. Most of the studies were of poor methodological quality or had a high risk of bias, with a mean score of 2.125 on the Jadad scale. No study could be classified as double-blind, and only one study documented the increased efficacy of insulin glargine in relation to both glycaemic control and hypoglycaemic episodes. Typically, there was no significant difference between insulin glargine and NPH insulins.
  
  
  CONCLUSIONS
  This systematic review showed no therapeutic benefit of insulin glargine over other insulin formulations studied when analysing together glycaemic control and the frequency and severity of hypoglycaemia. We therefore recommend to the State Authority to delist insulin glargine or renegotiate a price reduction with the manufacturer. This systematic review provides support for this decision as well as documentation to combat potential law suits if discussions are unsatisfactory.
authors.affiliation: Medical College, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos, 6627, Bloco 02, sl 1048, CEP 31270-901, Belo Horizonte, MG, Brazil, analuisacaires@gmail.com.
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Caires de Souza
authors.forename: Francisco
authors.initials: F
authors.lastname: de Assis Acurcio
authors.forename: Augusto Afonso
authors.initials: AA
authors.lastname: Guerra Júnior
authors.forename: Renata Cristina
authors.initials: RC
authors.lastname: Rezende Macedo do Nascimento
authors.forename: Brian
authors.initials: B
authors.lastname: Godman
authors.forename: Leonardo Maurício
authors.initials: LM
authors.lastname: Diniz
mesh_terms: D001938:Brazil; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000191:economics; D016527:Drug Costs; D004341:Drug Evaluation; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D011306:Prescription Fees; D016032:Randomized Controlled Trials as Topic
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D007336:Insulin, Isophane