Clinical Effectiveness and Safety of Analog Glargine in Type 1 Diabetes: A Systematic Review and Meta-Analysis

Lays P Marra, Vania E Araújo, Thales B C Silva, Leonardo M Diniz, Augusto A Guerra Junior, Francisco A Acurcio, Brian Godman, Juliana Álvares, Lays P Marra, Vania E Araújo, Thales B C Silva, Leonardo M Diniz, Augusto A Guerra Junior, Francisco A Acurcio, Brian Godman, Juliana Álvares

Abstract

Introduction: The use of insulin analogs for the treatment of type 1 diabetes mellitus (T1DM) is widespread; however, the therapeutic benefits still require further evaluation given their higher costs. The objective of this study was to evaluate the effectiveness and safety of analog insulin glargine compared to recombinant DNA (rDNA) insulin in patients with T1DM in observational studies, building on previous reviews of randomized controlled trials comparing neutral protamine Hagedorn insulin and insulin glargine.

Methods: A systematic review with a meta-analysis was performed. The review included cohort studies and registries available on PubMed, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as manual and gray literature searches. The meta-analysis was conducted in Review Manager 5.3 software. The primary outcomes were glycated hemoglobin (Hb1Ac), weight gain, and hypoglycemia. Methodological quality was assessed using the Newcastle-Ottawa scale.

Results: Out of 796 publications, 11 studies were finally included. The meta-analysis favored insulin glargine in HbA1c outcomes (adult patients) and hypoglycemic episodes (P < 0.05), but without reaching glycemic control (Hb1Ac to approximately 7%). The methodological quality of the studies was moderate, noting that 45% of studies were funded by pharmaceutical companies.

Conclusion: Given the high heterogeneity of the studies, the discrete value presented by the estimated effect on effectiveness and safety, potential conflicts of interest of the studies, and the appreciable higher cost of insulin glargine, there is still no support for recommending first-line therapy with analogs. The role of analogs in the treatment of T1DM could be better determined by further observational studies of good methodological quality to assess their long-term effectiveness and safety, as well as their cost-effectiveness.

Keywords: Comparative effectiveness research; Glargine; Insulin; Meta-analysis; Systematic review; Type 1 diabetes mellitus.

Figures

Fig. 1
Fig. 1
The process of study selection
Fig. 2
Fig. 2
Funnel plot of MD in HbA1c. MD mean difference, SE standard error
Fig. 3
Fig. 3
Glycated hemoglobin meta-analysis: age subgroup. CI confidence interval, df degrees of freedom, NPH neutral protamine Hagedorn, SD standard deviation, Method IV Method based on an iterative estimate and a closed form confidence interval
Fig. 4
Fig. 4
Meta-analysis: episodes of severe hypoglycemia. CI confidence interval, df degrees of freedom, NPH neutral protamine Hagedorn, SD standard deviation, Method IV Method based on an iterative estimate and a closed form confidence interval
Fig. 5
Fig. 5
Glycated hemoglobin meta-analysis: duration of the study subgroup. CI confidence interval, df degrees of freedom, NPH neutral protamine Hagedorn, SD standard deviation, Method IV Method based on an iterative estimate and a closed form confidence interval
Fig. 6
Fig. 6
Glycated hemoglobin meta-analysis: conflict of interest subgroup. CI confidence interval, df degrees of freedom, NPH neutral protamine Hagedorn, SD standard deviation, Method IV Method based on an iterative estimate and a closed form confidence interval

References

    1. Pasqualotto KR, Alberton D, Frigeri HR. Diabetes mellitus and complications. J Biotechnol Biodivers. 2012;3(4):134–145.
    1. Lepore M, Pampanelli S, Fanelli C, et al. Pharmacokinetica and pharmacodynamics of subcutaneous injection of long-acting human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000;49:2142–2148. doi: 10.2337/diabetes.49.12.2142.
    1. Caires de Souza AL, de Assis Acurcio F, Guerra Júnior AA, Rezende Macedodo Nascimento RC, Godman B, Diniz LM. Insulin glargine in a Brazilian state: should the government disinvest? An assessment based on a systematic review. Appl Health Econ Health Policy. 2014;12(1):19–32. doi: 10.1007/s40258-013-0073-6.
    1. Micromedex® Healthcare Series. Drugdex® Evaluations. Available from: . Accessed Nov 10, 2010.
    1. American Diabetes Association Standards of medical care in diabetes. Position statement. Diabetes Care. 2007;30(Suppl. 1):S4–S41. doi: 10.2337/dc07-S004.
    1. Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedlak M, Heise T. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care. 2000;23(5):644–649. doi: 10.2337/diacare.23.5.644.
    1. Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE. Defining the relationship between plasma glucose and HbA1c analysis of glucose profiles and HbA1c in the Diabetes Control and Complications Trial. Diabetes Care. 2002;25(2):275–278. doi: 10.2337/diacare.25.2.275.
    1. Sanches ACC, Correr CJ, Venson R, et al. Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety. Braz J Pharm Sci. 2013;49(3):501–509. doi: 10.1590/S1984-82502013000300011.
    1. Institutfürqualität und WirtschaftlichkeitimGesundheitswesen [Institute of Quality and Efficiency in Health Care]. Long-acting insulin analogues in the treatment of diabetes mellitus type 1 (2010). Available from: . Accessed May 2015.
    1. Institute for Quality and Efficiency in Health Care—IQWIG Long acting insulins for the treatment of diabetes mellitus type 1—Documentation. 2008. Available from: . Accessed May 2015.
    1. Szypowska A, Golicki D, Groele L, Pańkowska E. Long-acting insulin analogue detemir compared with NPH insulin in type 1 diabetes. Pol Arch Med Wewn. 2011;121:237–246.
    1. Schreiber SA, Russmann A. Long-term efficacy of insulin glargine therapy with an educational programme in type 1 diabetes patients in clinical practice. Curr Med Res Opin. 2007;23(12):3131–3136. doi: 10.1185/030079907X242827.
    1. Johansen OE. VanbergPJ, Kilhovd BK, Jørgensen AP. Changing basal insulin from NPH to detemir or glargine in patients with type 1 diabetes and a history of severe hypoglycemia. Vasc Health Risk Manag. 2009;5(1):121–128.
    1. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–2012. doi: 10.1001/jama.283.15.2008.
    1. Hartling L, Hamm M, Milne A, et al. Validity and inter rater reliability testing of quality assessment instruments [internet]. Appendix E, decision rules for application of the Newcastle-Ottawa Scale. Agency for Healthcare Research and Quality (US), Rockville (MD). Available from: . 2012.
    1. Higgins JPT, et al., editors. Cochrane handbook for systematic reviews of interventions. Chichester: Wiley-Blackwell; 2008.
    1. Garg SK, Paul JM, Karsten JI, Menditto L, Gottlieb PA. Reduced severe hypoglycemia with insulin glargine in intensively treated adults with type 1 diabetes. Diabetes Technol Ther. 2004;6(5):589–595. doi: 10.1089/dia.2004.6.589.
    1. Yamamoto-Honda R, Takahashi Y, Yoshida Y, et al. Use of insulin glargine in japanese patients with type 1 diabetes. Intern Med. 2007;46(13):937–943. doi: 10.2169/internalmedicine.46.6467.
    1. Colino E, López-Capapé M, Golmayo L, Alvarez MA, Alonso M, Barrio R. Therapy with insulin glargine (Lantus1) in toddlers, children and adolescents with type 1 diabetes. Diabetes Res Clin Pract. 2005;70(1):1–7. doi: 10.1016/j.diabres.2005.02.004.
    1. Dixon B, Chase HP, Burdick J, et al. Use of insulin glargine in children under age 6 with type 1 diabetes. Pediatr Diabetes. 2005;6(3):150–154. doi: 10.1111/j.1399-543X.2005.00115.x.
    1. Hathout EH, Fujishige L, Geach J, Ischandar M, Maruo S, Mace JW. Effect of therapy with insulin glargine (Lantus®) on glycemic control in toddlers, children, and adolescents with diabetes. Diabetes Technol Ther. 2003;5(5):801–806. doi: 10.1089/152091503322527003.
    1. Päivärinta M, Tapanainen P, Veijola R. Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes. Pediatr Diabetes. 2008;9:83–90. doi: 10.1111/j.1399-5448.2007.00341.x.
    1. Salemyr J, Bangand P, Örtqvist E. Lower HbA1c after 1 year, in children withtype1 diabetes treated with insulin glargine vs. NPH insulin from diagnosis: a retrospective study. Pediatr Diabetes. 2011;12(5):501–505. doi: 10.1111/j.1399-5448.2010.00723.x.
    1. Herwig J, Schöll-Schilling G, Böhles H. Glycaemic control and hypoglycaemia in children, adolescents and young adults with unstable type 1 diabetes mellitus treated with insulin glargine or intermediate-acting insulin. J Pediatr Endocrinol Metab. 2007;20(4):517–525. doi: 10.1515/JPEM.2007.20.4.517.
    1. Haukka J, Hoti F, Erästö P, Saukkonen T, Mäkimattila S, Korhonen P. Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study. Pharmacoepidemiol Drug Saf. 2013;22(12):1326–1335. doi: 10.1002/pds.3534.
    1. Marley J. Efficacy, effectiveness, efficiency. Aust Prescr. 2000;23:114–115. doi: 10.18773/austprescr.2000.131.
    1. Pereira C, Veiga N. Educação Para a Saúde Baseada em Evidências. 2014.
    1. Malmström RE, Godman BB, Diogene E, et al. Dabigatran - a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs. Front Pharmacol. 2013;14(4):39.
    1. Oliveira JEPD, Vencio S. Diretrizes da Sociedade Brasileira de Diabetes: 2014-2015. Sa˜o Paulo: AC Farmacêutica, 2015, pp. 1–360.
    1. Warren E, Weatherley-Jones E, Chilcott J, Beverley C. Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Health Technol Assess. 2004;8(45):iii, 1–57.
    1. Siebenhofer A, Plank J, Berghold A, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev. 2006;2:CD003287.
    1. Netto AP, Andriolo A, Filho FF, et al. Atualização sobre hemoglobina glicada (HbA1C) para avaliação do controle glicêmico e para o diagnóstico do diabetes: aspectos clínicos e laboratoriais. J Bras Patol Med Lab. 2009;45(1):31–48.
    1. Sacks DB. Hemoglobin variants and hemoglobin A1c analysis: problem solved? Clin Chem. 2003;49:1245–1247. doi: 10.1373/49.8.1245.
    1. Vardi M, Jacobson E, Nini A, Bitterman H. Intermediate acting versus long acting insulin for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2008;16(3):CD006297.
    1. Thompson DF. Understanding financial conflicts of interest. N Engl J Med. 1993;329:573–576. doi: 10.1056/NEJM199308193290812.
    1. Ggoldim JR. Conflito de interesses na área da saúde. 2007.
    1. Davis C, Abraham J. Is there a cure for corporate crime in the drug industry? BMJ. 2013;346:f755. doi: 10.1136/bmj.f755.
    1. Civaner M. Sale strategies of pharmaceutical companies in a “pharmerging” country: the problems will not improve if the gaps remain. Health Policy. 2012;106:225–232. doi: 10.1016/j.healthpol.2012.05.006.
    1. Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in biomedical research: a systematic review. JAMA. 2003;289(4):454–465. doi: 10.1001/jama.289.4.454.
    1. Ross JS, Tse T, Zarin DA, Xu H, Zhou L, Krumholz HM. Publication of NIH funded trials registered in : cross sectional analysis. BMJ. 2012;344(d7292):1–10.
    1. Pereira MG, Galvão TF. Heterogeneidade e viés de publicação em revisões sistemáticas. Epidemiologia e Serviços de Saúde. 2014;23(4):775–778. doi: 10.5123/S1679-49742014000400021.
    1. Heres S, Davis J, Maino K, Jetzinger E, Kissling W, Leucht S. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Am J Psychiatry. 2006;163(2):185–194. doi: 10.1176/appi.ajp.163.2.185.
    1. Wang F, Carabino JM, Vergara CM. Insulin glargine: a systematic review of a long-acting insulin analogue. Clin Ther. 2003;25(6):1541–1577. doi: 10.1016/S0149-2918(03)80156-X.

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