Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis

Abstract

Objective To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.Design Systematic review and network meta-analysis.Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.Study selection Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.Results 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference −0.39%, 95% confidence interval −0.59% to −0.19%; −0.26%, −0.48% to −0.03%; and −0.36%, −0.65% to −0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: −5.51 kg, −6.56 to −4.46 kg; glargine once daily versus NPH once daily: −5.14 kg, −6.07 to −4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.Conclusions Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.Systematic review registration PROSPERO CRD42013003610.

International trade and determinants of price differentials of insulin medicine

“…Empirical evidence shows that health outcomes, such as mortality, morbidity, and quality of life, are almost identical across different types of insulin. Some new insulin products are intermediate acting and therefore more convenient; however, their health effect is very similar to the older long-acting ones (e.g., Tricco et al 2014). Second, the insulin industry can be described as oligopolistic, as three manufacturers dominate the world market.…”

Essential medicines and access to insulin

“…The systematic review described the benefits of analogues as "probably superior" to isophane insulin with respect to HbA 1c , with the authors noting that the "difference is small" and "no differences are likely to be clinically relevant"; for costeffectiveness, the results "were inconsistent across studies". 5 We therefore agree with the conclusions of the Editorial that access to human insulin is still "despairingly low" for many patients worldwide and that adding more expensive insulins to the WHO model list is not likely to improve this situation. 1 We trust that WHO will reject this application.…”

“…The evidence base for the superiority of analogue insulins is also weak. The application to WHO is supported by a systematic review and network meta-analysis 5 that largely comprised open-label, manufacturer-sponsored studies. As a result, in the submission's summary tables, all but two studies are described as at serious or very serious risk of bias.…”

Análise das demandas judiciais de medicamentos junto a Secretaria de Estado da Saúde de São Paulo à luz da política de assistência farmacêutica

“…É preciso avaliar se os benefícios advindos das insulinas análogas justificam os gastos adicionais com o seu fornecimento (Wang et al, 2011). Estudos de revisão sistemática de ensaios clínicos concluíram que insulinas análogas de longa duração oferecem pouca ou nenhuma vantagem clínica em relação a NPH em adultos com diabetes Tipo I (Sanches et al, 2011;Souza et al, 2014); os resultados mostram diferenças estatisticamente significantes entre as insulinas análogas e a NPH, porém, do ponto de vista clínico, a diferença não é considerada relevante (Tricco et al, 2014). Em relação ao diabetes Tipo II, para os desfechos de controle metabólico, não houve significância estatística na comparação entre os tratamentos com as insulinas análogas e NHP (Horvath et al, 2007).…”

“…Muitos destes estudos apontam algum tipo de financiamento, pela indústria farmacêutica, do estudo ou do pesquisador (Sanches et al, 2011;Tricco et al, 2014;Souza et al, 2014;Garber, 2014). Gotzsche (2016), em livro recentemente publicado, aponta os perigos para a sociedade das pesquisas financiadas pela indústria farmacêutica.…”