Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

Abstract

All patients with Diabetes Mellitus (DM) receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily) and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I 2 =0%). Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety.Our results indicate that long-and short-acting insulin analogues offer few clinical advantages over conventional human insulin. Uniterms:Insulins/meta-analysis. Diabetes mellitus/type 1. Insulin/treatment efficacy. Insulin/safety use.Todos os pacientes com Diabetes Mellitus (DM) tipo 1 recebem insulina. Neste estudo, avaliaram-se eficácia, segurança e tolerabilidade de insulinas humanas e análogas. Realizou-se uma revisão sistemática e meta-análise, de acordo com o preconizado pela Colaboração Cochrane. Na ausência de estudos clínicos comparando insulinas entre si, realizaram-se meta-análises de comparações indiretas a fim de estabelecer diferenças entre tratamentos ativos. Incluíram-se estudos de 1995 a 2010. Resultados de HbA1c, episódios de hipoglicemia e hipoglicemia noturna foram extraídos e analisados. Após leitura de resumos e, posteriormente, de artigos na íntegra, selecionaram-se 35 ensaios clínicos randomizados, totalizando 4206 pacientes utilizando insulina análoga de longa duração e 5733 pacientes insulina análoga de curta duração. Os resultados não demonstraram diferença estatisticamente significativa para redução de HbA1c entre glargina e detemir (uma vez ao dia) comparados a NPH. No entanto, insulina detemir utilizada duas vezes ao dia reduz a HbA1c (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I 2 =0%). Comparações diretas e indiretas indicam que não existem diferenças significativas na médica de redução de HbA1c, independente da posologia de detemir, sendo estes resultados de eficácia e segurança consistentes. Os resultados indicam que insulinas análogas de longa ou curta duração apresentam pequenas vantagens, quando comparadas às insulinas tradicionais. Ademais, não existem diferenças entre eficácia e seguran...

Cost-effectiveness of insulin analogs from the perspective of the Brazilian public health system

“…According to the analysis by the values of Odds Ratio (OR) between the comparisons of total episodes of hypoglycemia, the meta-analysis used in this study has shown: detemir vs. (Sanches et al, 2013). It is noteworthy that the analysis performed in this study did not consider the cost of adverse reactions of the insulins.…”

“…Thus, the cost per IU of the drug was multiplied by the mean daily dose in IU recommended for each type of insulin, and calculated per patient/year. The mean dose values assigned to each type of insulin were extracted from the studies used in the meta-analysis by Sanches et al (2013) (Anderson Jr et al, 1997;Home, 2000;Hermansen et al, 2004;Heller, Koenen, Bode, 2009).…”

“…Data related to the reduction of HbA1c were used to compare treatment with human insulin and treatment with insulin analogs, being obtained from the meta-analysis by Sanches et al (2013). The meta-analysis examined sixteen studies, totaling 5,733 patients using rapid-acting insulin analogs (glulisine, arpart, lispro) and 4,771 patients using long-acting insulin analogs (glargine and detemir).…”

“…The mean age was 39.2 years and all patients were receiving diabetes treatment with insulin only. Glulisine was excluded from this study because it was not analyzed in the meta-analysis, being as it was found only in a clinical trial that analyzed glulisine vs. insulin R. The meta-analysis considered the significance level of 5% and the figures were interpreted for 95% confidence interval (Sanches et al, 2013).…”

New insulins and newer insulin regimens: a review of their role in improving glycaemic control in patients with diabetes

“…A recent meta-analysis comparing long-acting analogues (glargine or detemir, used once daily) and NPH insulin showed no significant differences in HbA1c outcomes. However, twice-daily detemir showed a modest HbA1c benefit to NPH insulin in comparative studies (mean difference=−0.14%; 95% CI −0.21 to −0.08) 23. Direct comparisons between basal analogues and NPH insulin on patient-reported outcomes including quality of life and treatment satisfaction are lacking.…”