Rapid and Sensitive Analytical Method for the Determination of Insulin in Liposomes by Reversed-Phase HPLC.

Insulin is an important anabolic hormone that regulates the metabolism of carbohydrates, lipids and proteins. In this study, a reverse-phase liquid chromatography (RP-LC) method was successfully validated and tested for the encapsulation efficiency assay of insulin and in vitro release studies. HPLC analyses were carried out using a RP C18- Luna® Phenomenex (4.6 × 250 mm, 5 ?m particle size) column maintained at room temperature, using a mobile phase constituted by a mixture of acetonitrile and 0.1% TFA aqueous solution (60:40, v/v), in an isocratic mode with a flow rate of 1.0 mL/ min, with ultraviolet detection at 214 nm and 20 ?L of injection volume. Method validation was performed according recognized guidelines for system suitability, specificity, linearity, precision, accuracy, LOD, LOQ and robustness. The method was shown to be linear in the range of 0.5-100 ?g/mL (r2 = 0.9993) selective, precise, robust, accurate with LOD and LOQ values were 0.097 ?g/mL and 0.294 ?g/mL, respectively. The developed method proved to be adequate to analyze the encapsulation efficiency and the profile of insulin release from liposomes.

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

ABSTRACT Human insulin is provided by the Brazilian Public Health System (BPHS) for the treatment of diabetes, however, legal proceedings to acquire insulin analogs have burdened the BPHS health system. The aim of this study was to perform a cost-effectiveness analysis to compare insulin analogs and human insulins. This is a pharmacoeconomic study of cost-effectiveness. The direct medical cost related to insulin extracted from the Ministry of Health drug price list was considered. The clinical results, i.e. reduction in glycated hemoglobin (HbA1c), were extracted by meta-analysis. Different scenarios were structured to measure the uncertainties regarding the costs and reduction in HbA1c. Decision tree was developed for sensitivity of Incremental Cost Effectiveness Ratio (ICER). A total of fifteen scenarios were structured. Given the best-case scenario for the insulin analogs, the insulins aspart, lispro, glargine and detemir showed an ICER of R$ 1,768.59; R$ 3,308.54; R$ 11,718.75 and R$ 2,685.22, respectively. In all scenarios in which the minimum effectiveness was proposed, lispro, glargine and detemir were dominant strategies. Sensitivity analysis showed that the aspart had R$ 3,066.98 [95 % CI: 2339.22; 4418.53] and detemir had R$ 6,163.97 [95% CI: 3919.29; 11401.57] for incremental costs. We concluded there was evidence that the insulin aspart is the most cost-effective.

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

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; I²=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.

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; I²=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 segurança quando comparamos insulinas análogas entre si.