Comment on: “Insulin Glargine in a Brazilian State: Should the Government Disinvest?”

Abstract

Published online: 14 August 2014© Springer International Publishing Switzerland 2014Dear Editor,I read with interest the article Insulin Glargine in a Bra- zilian State: Should the Government Disinvest? An Assessment Based on a Systematic Review, authored by Caires de Souza et al. [1], which appeared in the February 2014 issue of Applied Health Economics and Health Policy.As a clinician, I cannot agree with several points raised by the article.Insulin analogs clearly represent a milestone in the history of insulin therapy since its beginning in 1923. They have pharmaceutical properties that greatly facilitated insulin use and improved safety for both patients and cli- nicians; namely, pharmacodynamic stability, reproducibil- ity of action, and a more physiological timing of action. These advantages are clear for both those who treat and those who are treated for insulin-dependent or insulin- requiring diabetes: insulin analogs are better drugs than biosynthetic human insulin, and this is the basis for the increasing popularity of and demand for insulin analogs, despite their higher cost.Caires de Souza et al. [1] seem to have prepared their review with the primary motivation of justifying-on both administrative and juridical grounds-the government's denial of insulin analogs to diabetic patients who need them. However, by starting from this premise, they failed to address the several clinical guidelines that exist on this topic in Brazil, seem to have distorted their own data, and also failed to address the central matters of ill management and sub-financing of public health services in Brazil.The process by which the studies for review were identified and selected seems inappropriate and flawed from the start, as studies on insulin glargine began in the late 1990s (not in 1970), and important data have been published since 2009. Of the eight papers selected for analysis, five were considered of poor quality and/or to have a high risk of bias according to the authors' own criteria; one should never have been included, as it com- pares two forms of insulin analog delivery and not insulin glargine versus neutral protamine Hagedorn (NPH) insulin; and one had a follow-up of only 4 months. As for the outcome measures analyzed, five of the studies reported improved fasting glycemia and/or glycated hemoglobin (HbA1c) with glargine. Two studies found smaller and one found higher hypoglycemia rates with glargine, the remaining five studies showing no difference versus NPH. However, the gold-standard outcome measure for hypo- glycemia-rates among patients reaching HbA1c goals- was not analyzed, and here glargine systematically per- forms better than NPH. Thus, there is little medical science and investigative effort and much tendentiousness.The cancer issue surrounding glargine was defini- tively settled in 2012 after the publication of the ORI- GIN (Outcomes Reduction with an Initial Glargine Intervention) 7-year follow-up prospective study involving more than 12,000 patients [2]: insulin glargine has no effect on the incidence of cancer. The same holds for recent publications on the affinity of insulin glar- gine's active metabolites to the insulin-like growth factor (IGF)-1 receptor [3, 4] and on its relationship with the evolution of retinopathy, which has been shown to be unaffected by insulin glargine [5]. Had Caires de Souza et al. [5] extended their literature search beyond 2009, improper discussions on this matter would have been avoided.In terms of the various reviews and health authority deliberations cited by the authors regarding the lack of evidence for the increased effectiveness and safety of the insulin analogs, it can be said that randomized controlled trials can only partially mimic real-life conditions, and that bureaucratic analyses cannot overrule clinical evidence. Insulin analogs are better insulins, and patients who need but do not get them are hardly represented in the trials. …