Análogos de insulina
¿Qué son, por qué, y cómo usarlos en la práctica médica?
Palabras clave:
DIABETES MELLITUS, INSULINA - ANÁLOGOS & DERIVADOS, INSULINA - FARMACOLOGÍA
Resumen
En 1922 se inyectó por primera vez insulina a un paciente con diabetes. Desde entonces hasta el momento actual la industria farmacéutica desarrolló insulinas iguales a la humana y con perfiles de acción y metabolización que intentan reproducir la forma en que el páncreas segrega insulina al torrente circulatorio en respuesta a las comidas y al ayuno, o sea intentando reproducir la secreción fisiológica de insulina. Mediante técnicas de bioingeniería, la molécula de insulina ha sido alterada, cambiando la secuencia de algunos aminoácidos de sus cadenas (análogos) con lo que se han obtenido algunas fórmulas que brindan un perfil de acción muy rápido -útiles para imitar las excursiones posprandiales- y otras de acción prolongada con las que se puede imitar la secreción basal de insulina.
El propósito de este trabajo fue realizar una revisión de la secreción fisiológica de insulina; los fundamentos para la creación de los análogos de insulina y su farmacocinética; las dificultades en el uso de las insulinas convencionales; las evidencias existentes de los beneficios del uso de análogos y la forma de usarlos.
Citas
(1) Scolpini V. Historia de la diabetes en el Uruguay. Obtenido de: http://www.smu.org.uy/historia/articulos/hist_diab.pdf (Consulta: 10 abr 2006).
(2) The history of insulin. Obtenido de: http://www.med.uni-giessen.de/itr/history/inshist.html (Consulta: 10 abr 2006).
(3) Pisciotano C. Insulinoterapia en diabetes en el niño y adolescente. Montevideo: Prensa Médica Latinoamericana, 1996: 53-66.
(4) The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329 (14): 977-86
(5) UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352 (9131): 837-53.
(6) Rolla A. Insulin analogs: when oral therapies fail: treatment options for better control. Overcoming the limitations of conventional insulins. Obtenido de: http://www.baylorcme.org/index.cfm (Consulta: 12 ene 2005).
(7) Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28(2): 103-17.
(8) Reichard P, Berglund B, Britz A, Cars I, Nilsson BY, Rosenqvist U. Intensified conventional insulin treatment retards the microvascular complications of insulin dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDID) after 5 years. J Intern Med 1991; 230(2): 101-8.
(9) DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2- hour diagnostic criteria. Arch Intern Med 2001; 161(3): 397-405.
(10) American Diabetes Association. Standards of medical care in diabetes-2006. Diabetes Care 2006; 29 (Suppl 1): S4-42.
(11) American Association of Clinical Endocrinologists. American College of Endocrinology. Medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management-2002 update. Endocr Pract 2002; 8 (Suppl 1):40-82.
(12) Koro CE, Bowlin SJ, Borgeois N, Fedder DO. Glycemic control from 1988 to 2000 from US adults diagnosed with type 2 diabetes: A preliminary report. Diabetes Care 2004; 27 (1): 17-20.
(13) Saaddine JB, Cadwell B, Gregg EW, Engelgau MM, Vinicor F, Imperatore G, et al. Improvements in diabetes processes of care and intermediate outcomes: United States, 1988-2002. Ann Intern Med 2006; 144: 465-74.
(14) U.K. Prospective Diabetes Study Group. U.K. prospective diabetes study 16, Overview of 6 years´ therapy of type II diabetes: a progressive disease. Diabetes 1995; 44 (11): 1249-58.
(15) The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial: A randomized, controlled trial. Ann Intern Med 1998; 128: 517-23.
(16) Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care 2004: 27(5): 1028-35.
(17) Li Y, Xu W, Liao Z, Yao B, Chen X, Huang Z, et al. Induction of long term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvements of B cell function. Diabetes Care 2004; 27(11): 2595-602.
(18) Larger E. Weight gain and insulin treatment. Diabetes Metab 2005; (4Pt 2): 4S51-4S56.
(19) Hirsch IB. Insulin analogues. N Eng J Med 2005; 352: 174-83.
(20) Eli Lilly and Company. Humalog® insulin lispro injection. Prescribing information. Indianápolis, 2004. Obtenido de: http://pi.lilly.com/us/humalog-pen-pi.pdf (Consulta: 10 abr 2006).
(21) Novo Nordisk Inc. NovoLog® (insulin aspart). Prescribing information. Princeton, 2003. Obtenido de: http://www.novolog.com/consumer/assets/NovoLog_Prescribing_ Info.pdf (Consulta: 10 abr 2006).
(22) Aventis Pharmaceuticals Inc. Apidra (insulin glulisine [rDNA origin] injection). Prescribing information. Kansas, 2004.Obtenido de: http://products.sanofi-aventis.us/apidra/apidra.html (Consulta: 10 abr 2006).
(23) Aventis Pharmaceuticals Inc. Lantus (insulin glargine [rDNA origin] injection). Prescribing information. Kansas, 2003.Obtenido de: http://products.sanofi-aventis.us/lantus/lantus.html (Consulta: 10 abr 2006).
(24) Havelund S, Plum A, Ribel U, Jonassen I, Volund A, Markussen J, Kurtzhals P. The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharm Res 2004; 21: 1498-504.
(25) Heise T, Nosek L, Ronn BB, Endahl L, Heinemann L, Kapitza C, Draeger E. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin largine in people with type 1 diabetes. Diabetes 2004; 53: 1614-20.
(26) Skyler JS. Insulin treatment. In: Lebovitz H. ed. Therapy for diabetes mellitus and related disorders. 4 ed. Alexandria: American Diabetes Association, 2004: 207-223.
(27) Bolli G. Michael Berger Evidence-based Medicine Debate: therapeutic benefits of insulin analogues: "pro". Annual Meeting of the EASD, 41. (Athens, 13 set 2005). Obtenido de: http://easd-lectures.org/index.php?menu=view&chart= 2&id=91 (Consulta: 6 abr 2006).
(28) Heinemann L, Weyer C, Rauaus M, Heinrichs S, Heise T. Variability of the metabolic effect of soluble insulin and the rapid acting analog insulin aspart. Diabetes Care 1998, 21: 1910-4.
(29) Pisciotano C, García M V, Agazzi B, Melone I, Soñora M, Gasagoite J. Ensayo clínico comparativo en terapia intensiva con el uso de Insulina NPH y regular y con insulina NPH y lyspro en diabéticos tipo 1 de 8 a 15 años. Congreso Brasileiro de Diabetes, 12 (Aracaju-Brasil, 10-14 oct 1999)
(30) Siebenhofer A, Plank J, Berghold A, Narath M, Gfrerer R, Pieber TR. Análogos de insulina de acción rápida versus Insulina Humana Corriente en pacientes con diabetes mellitus (Revisión Cochrane traducida). Obtenido de: http//www.update-software.com (Consulta: 22 mar 2006).
(31) Pieber T. Michael Berger Evidence-based Medicine Debate: therapeutic benefits of insulin analogues: "contra". Annual Meeting of the EASD, 41. (Athens, 13 set 2005). Obtenido de: www.easd-lectures.org (Consulta: 6 abr 2006).
(32) Bolli GB. Insulin treatment in type 1 diabetes. Endocr Pract 2006; 12 (Suppl 1): 105-9.
(33) Hermansen K, Fontaine P, Kukolja K, Peterkova V, Leth G, Gall M. Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal bolus therapy for patients with Type 1 diabetes. Diabetología 2004; 47: 622-9.
(34) Christiansen JS, Vaz JA, Metelko Z, Bogoev M, Dedov I. Twice daily biphasic insulin aspart improves postprandial glycaemic control more effectively than twice daily NPH insulin, with low risk of hypoglycaemia, in patients with type 2 diabetes. Diabetes Obes Metab 2003; 5(6): 446-54.
(35) Russel Jones D, Simpson R, Hylleberg B, Draeger E, Bolindre J. Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen. Clin Ther 2004; 26(5): 724-36.
(36) Home PD, Rosskamp R, Forjanic-Klapproth J, Dressler A, European Insulin Glargine Study Group. A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes. Diabetes Metab Res Rev 2005; 21(6): 545-53.
(37) Fulcher GR, Gilbert RE, Yue DK. Glargine is superior to neutral protamine Hagedorn for improving glycated haemoglobin and fasting blood glucose levels during intensive insulin therapy. Intern Med J 2005; 35(9): 536-42.
(38) Rossetti P, Pampanelli S, Fanelli C, Porcellati F, Costa E, Torlone E, et al. Intensive replacement of basal insulin in patients with type 1 diabetes given rapid-acting insulin analog at mealtime: a 3-month comparison between administration of NPH insulin four times daily and glargine insulin at dinner or bedtime. Diabetes Care 2003; 26(5): 1490-6.
(39) Pieber TR, Draeger E, Kristensen A, Grill V. Comparison of three multiple injection regimens for Type 1 diabetes: morning plus dinner or bedtime administration of insulin detemir vs morning plus bedtime NPH insulin. Diabet Med 2005; 22(7): 850-7.
(40) Davies M, Storms F, Shutler S, Bianchi-Biscay M, Gomis R, ATLANTUS Study Group. Improvements of glycemic control in subjects with poorly controlled type 2 diabetes. Diabetes Care 2005; 28: 1282-8.
(41) Bott U, Ebrahim S, Hirschberger S, Skovlund S. Effect of the rapid-acting insulin analogue insulin aspart on quality of life and treatment satisfaction in patients with Type 1 diabetes. Diabet Med 2003; 20(8): 626-34.
(42) Bradley C, Speight J. Patient perceptions of diabetes and diabetes therapy: assessing quality of life. Diabetes Metab Res Rev 2002; 18 (Suppl 3): S64-9.
(43) Raskin P, Allen E, Hollander P, Lewin A, Gabbay RA, Hu P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care 2005; 28: 260-5.
(44) Malone JK, Bai S, Campaigne BN, Reviriego J, Augendre- Ferrante B. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes. Diabet Med 2005; 22: 374-81.
(45) Garber A, Wahlen J, Wahl T, Bressler P, Braceras R, Allen E, Jain R. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (The 1-2-3 study). Diabetes Obes Metab 2006; 8(1): 58-66.
(46) Janka H, Plewe G, Riddle M, Kliebe- Friesch C, Schweitzer M, Yki- Jarvinen H. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin. Diabetes Care 2005; 28: 254-9.
(47) Dailey G. New strategies for basal insulin treatment in type 2 diabetes mellitus. Clin Ther 2004; 26(6): 889-901.
(48) Riddle M, Rosenstock J, Gerich J, Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabet Care 2003; 26(11): 3080-6.
(2) The history of insulin. Obtenido de: http://www.med.uni-giessen.de/itr/history/inshist.html (Consulta: 10 abr 2006).
(3) Pisciotano C. Insulinoterapia en diabetes en el niño y adolescente. Montevideo: Prensa Médica Latinoamericana, 1996: 53-66.
(4) The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329 (14): 977-86
(5) UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352 (9131): 837-53.
(6) Rolla A. Insulin analogs: when oral therapies fail: treatment options for better control. Overcoming the limitations of conventional insulins. Obtenido de: http://www.baylorcme.org/index.cfm (Consulta: 12 ene 2005).
(7) Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28(2): 103-17.
(8) Reichard P, Berglund B, Britz A, Cars I, Nilsson BY, Rosenqvist U. Intensified conventional insulin treatment retards the microvascular complications of insulin dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDID) after 5 years. J Intern Med 1991; 230(2): 101-8.
(9) DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2- hour diagnostic criteria. Arch Intern Med 2001; 161(3): 397-405.
(10) American Diabetes Association. Standards of medical care in diabetes-2006. Diabetes Care 2006; 29 (Suppl 1): S4-42.
(11) American Association of Clinical Endocrinologists. American College of Endocrinology. Medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management-2002 update. Endocr Pract 2002; 8 (Suppl 1):40-82.
(12) Koro CE, Bowlin SJ, Borgeois N, Fedder DO. Glycemic control from 1988 to 2000 from US adults diagnosed with type 2 diabetes: A preliminary report. Diabetes Care 2004; 27 (1): 17-20.
(13) Saaddine JB, Cadwell B, Gregg EW, Engelgau MM, Vinicor F, Imperatore G, et al. Improvements in diabetes processes of care and intermediate outcomes: United States, 1988-2002. Ann Intern Med 2006; 144: 465-74.
(14) U.K. Prospective Diabetes Study Group. U.K. prospective diabetes study 16, Overview of 6 years´ therapy of type II diabetes: a progressive disease. Diabetes 1995; 44 (11): 1249-58.
(15) The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial: A randomized, controlled trial. Ann Intern Med 1998; 128: 517-23.
(16) Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care 2004: 27(5): 1028-35.
(17) Li Y, Xu W, Liao Z, Yao B, Chen X, Huang Z, et al. Induction of long term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvements of B cell function. Diabetes Care 2004; 27(11): 2595-602.
(18) Larger E. Weight gain and insulin treatment. Diabetes Metab 2005; (4Pt 2): 4S51-4S56.
(19) Hirsch IB. Insulin analogues. N Eng J Med 2005; 352: 174-83.
(20) Eli Lilly and Company. Humalog® insulin lispro injection. Prescribing information. Indianápolis, 2004. Obtenido de: http://pi.lilly.com/us/humalog-pen-pi.pdf (Consulta: 10 abr 2006).
(21) Novo Nordisk Inc. NovoLog® (insulin aspart). Prescribing information. Princeton, 2003. Obtenido de: http://www.novolog.com/consumer/assets/NovoLog_Prescribing_ Info.pdf (Consulta: 10 abr 2006).
(22) Aventis Pharmaceuticals Inc. Apidra (insulin glulisine [rDNA origin] injection). Prescribing information. Kansas, 2004.Obtenido de: http://products.sanofi-aventis.us/apidra/apidra.html (Consulta: 10 abr 2006).
(23) Aventis Pharmaceuticals Inc. Lantus (insulin glargine [rDNA origin] injection). Prescribing information. Kansas, 2003.Obtenido de: http://products.sanofi-aventis.us/lantus/lantus.html (Consulta: 10 abr 2006).
(24) Havelund S, Plum A, Ribel U, Jonassen I, Volund A, Markussen J, Kurtzhals P. The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharm Res 2004; 21: 1498-504.
(25) Heise T, Nosek L, Ronn BB, Endahl L, Heinemann L, Kapitza C, Draeger E. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin largine in people with type 1 diabetes. Diabetes 2004; 53: 1614-20.
(26) Skyler JS. Insulin treatment. In: Lebovitz H. ed. Therapy for diabetes mellitus and related disorders. 4 ed. Alexandria: American Diabetes Association, 2004: 207-223.
(27) Bolli G. Michael Berger Evidence-based Medicine Debate: therapeutic benefits of insulin analogues: "pro". Annual Meeting of the EASD, 41. (Athens, 13 set 2005). Obtenido de: http://easd-lectures.org/index.php?menu=view&chart= 2&id=91 (Consulta: 6 abr 2006).
(28) Heinemann L, Weyer C, Rauaus M, Heinrichs S, Heise T. Variability of the metabolic effect of soluble insulin and the rapid acting analog insulin aspart. Diabetes Care 1998, 21: 1910-4.
(29) Pisciotano C, García M V, Agazzi B, Melone I, Soñora M, Gasagoite J. Ensayo clínico comparativo en terapia intensiva con el uso de Insulina NPH y regular y con insulina NPH y lyspro en diabéticos tipo 1 de 8 a 15 años. Congreso Brasileiro de Diabetes, 12 (Aracaju-Brasil, 10-14 oct 1999)
(30) Siebenhofer A, Plank J, Berghold A, Narath M, Gfrerer R, Pieber TR. Análogos de insulina de acción rápida versus Insulina Humana Corriente en pacientes con diabetes mellitus (Revisión Cochrane traducida). Obtenido de: http//www.update-software.com (Consulta: 22 mar 2006).
(31) Pieber T. Michael Berger Evidence-based Medicine Debate: therapeutic benefits of insulin analogues: "contra". Annual Meeting of the EASD, 41. (Athens, 13 set 2005). Obtenido de: www.easd-lectures.org (Consulta: 6 abr 2006).
(32) Bolli GB. Insulin treatment in type 1 diabetes. Endocr Pract 2006; 12 (Suppl 1): 105-9.
(33) Hermansen K, Fontaine P, Kukolja K, Peterkova V, Leth G, Gall M. Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal bolus therapy for patients with Type 1 diabetes. Diabetología 2004; 47: 622-9.
(34) Christiansen JS, Vaz JA, Metelko Z, Bogoev M, Dedov I. Twice daily biphasic insulin aspart improves postprandial glycaemic control more effectively than twice daily NPH insulin, with low risk of hypoglycaemia, in patients with type 2 diabetes. Diabetes Obes Metab 2003; 5(6): 446-54.
(35) Russel Jones D, Simpson R, Hylleberg B, Draeger E, Bolindre J. Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen. Clin Ther 2004; 26(5): 724-36.
(36) Home PD, Rosskamp R, Forjanic-Klapproth J, Dressler A, European Insulin Glargine Study Group. A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes. Diabetes Metab Res Rev 2005; 21(6): 545-53.
(37) Fulcher GR, Gilbert RE, Yue DK. Glargine is superior to neutral protamine Hagedorn for improving glycated haemoglobin and fasting blood glucose levels during intensive insulin therapy. Intern Med J 2005; 35(9): 536-42.
(38) Rossetti P, Pampanelli S, Fanelli C, Porcellati F, Costa E, Torlone E, et al. Intensive replacement of basal insulin in patients with type 1 diabetes given rapid-acting insulin analog at mealtime: a 3-month comparison between administration of NPH insulin four times daily and glargine insulin at dinner or bedtime. Diabetes Care 2003; 26(5): 1490-6.
(39) Pieber TR, Draeger E, Kristensen A, Grill V. Comparison of three multiple injection regimens for Type 1 diabetes: morning plus dinner or bedtime administration of insulin detemir vs morning plus bedtime NPH insulin. Diabet Med 2005; 22(7): 850-7.
(40) Davies M, Storms F, Shutler S, Bianchi-Biscay M, Gomis R, ATLANTUS Study Group. Improvements of glycemic control in subjects with poorly controlled type 2 diabetes. Diabetes Care 2005; 28: 1282-8.
(41) Bott U, Ebrahim S, Hirschberger S, Skovlund S. Effect of the rapid-acting insulin analogue insulin aspart on quality of life and treatment satisfaction in patients with Type 1 diabetes. Diabet Med 2003; 20(8): 626-34.
(42) Bradley C, Speight J. Patient perceptions of diabetes and diabetes therapy: assessing quality of life. Diabetes Metab Res Rev 2002; 18 (Suppl 3): S64-9.
(43) Raskin P, Allen E, Hollander P, Lewin A, Gabbay RA, Hu P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care 2005; 28: 260-5.
(44) Malone JK, Bai S, Campaigne BN, Reviriego J, Augendre- Ferrante B. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes. Diabet Med 2005; 22: 374-81.
(45) Garber A, Wahlen J, Wahl T, Bressler P, Braceras R, Allen E, Jain R. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (The 1-2-3 study). Diabetes Obes Metab 2006; 8(1): 58-66.
(46) Janka H, Plewe G, Riddle M, Kliebe- Friesch C, Schweitzer M, Yki- Jarvinen H. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin. Diabetes Care 2005; 28: 254-9.
(47) Dailey G. New strategies for basal insulin treatment in type 2 diabetes mellitus. Clin Ther 2004; 26(6): 889-901.
(48) Riddle M, Rosenstock J, Gerich J, Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabet Care 2003; 26(11): 3080-6.
Publicado
2006-12-31
Cómo citar
1.
Serra Sansone M del P. Análogos de insulina. Rev. Méd. Urug. [Internet]. 31 de diciembre de 2006 [citado 17 de mayo de 2024];22(4):266-7. Disponible en: http://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/659
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