Insulin in the therapeutic scheme for type 2 diabetes mellitus
Authors:
Emil Martinka
Authors place of work:
Národný endokrinologický a diabetologický ústav, n. o., Ľubochňa
Published in the journal:
Forum Diab 2017; 6(2): 69-77
Category:
Topic
Summary
Insulin treatment in patients with type 2 diabetes mellitus (DM2T) is naturally needed as a result of their disease causing gradual reduction of their own insulin secretion. Although own insulin secretion in these patients only exceptionally falls below the limit that we still consider normal, a relative insufficiency of insulin in relation to the degree of insulin resistance already appears in the earlier stages of the disease. Insulin is a “medicine” with the strongest effect of lowering glycemia. The HbA1c target levels are attained in a greater number of patients as compared to OAD and the effect is long-term. Insulin can be used for patients with DM2T in the following ways: (1) As initial treatment for DM2T (with HbA1c > 9 %, or the clinical manifestations of hyperglycemia, or with glycemia levels > 14 mmol/l); (2) In combination with metformin (preferentially basal analogue); (3) In combination with all the groups of oral antidiabetics after preceding monotherapy or dual therapy of OAD; (4) As the ultimate treatment when the treatment with non-insulin antidiabetic drugs has failed. Insulin analogues (basal as well as prandial) have more advantageous pharmacokinetic properties, which is also why they are preferred. The most widespread method of initiating insulin treatment following OAD treatment is through basal insulin (preferentially the basal analogues glargine, detemir, degludec). An alternative initial regimen with HbA1c > 8.5 % is one using biphasic insulin. Intensification of basal insulin treatment was only possible by adding prandial insulin until recently. Currently it is also possible with the use of GLP1 receptor agonist, however only with a fixed combination of insulin degludec and liraglutide. Besides its impact on glycemia, insulin has also demonstrated numerous other effects. It affects the metabolism of fats, proteins, electrolytes and minerals. It has also demonstrated anti-inflammatory, antioxidant and endothelial protective effects. With regard to a cardiovascular risk/benefit it is neutral and it is safe as far as cancer risk is concerned. An early insulin treatment received by patients with newly diagnosed DM2T can lead to remission. The main undesirable effects include hypoglycemia and weight gain. A potentially increased morbidity and mortality risk associated with very high insulin doses has been a discussed topic.
Key words:
degludec, detemir, diabetes type 2 – DM2T, glargine, GLP1, insulin, insulin analogues, metformine, oral antidiabetic drugs
Received:
18. 4. 2017
Accepted:
2. 5. 2017
Zdroje
1. American Diabetes Association. Standards of Medical Care in Diabetes 2017. Diabetes Care 2017; 40(Suppl 1): S4-S5. Dostupné z DOI: <https://doi.org/10.2337/dc17-S003>.
2. Becker RH, Nowotny I, Teichert L et al. Low within- and between-day variability in exposure to new insulin glargine 300 U/ml. Diabetes Obes Metab 2015; 17(3): 261–267. <http://dx.doi.org/10.1111/dom.12416>.
3. Bergenstal R. Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml in people with type 1 diabetes (EDITION 4). EASD 2014. Wien. Poster 949.
4. Bi Y, Li X, Yang D et al. Comparative efficacy and safety of long-acting insulin analogs in patients with type 2 diabetes failing on oral therapy: Systemic review and meta-analyses. J Diabetes Investig 2012; 3(3): 283–293. Dostupné z DOI: <http://dx.doi.org/10.1111/j.2040–1124.2011.00187.x>.
5. Bode BW, Buse JB, Fisher M et al. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN(®) Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med 2013; 30(11): 1293–1297. Dostupné z DOI: <http://dx.doi.org/10.1111/dme.12243>.
6. Bonds DE, Miller ME, Bergenstal RM et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.b4909>.
7. Dandona P, Aljada A, Mohanty P. The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 2002; 45(6): 924–930. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–001–0766–5>.
8. Gerstein HC, Bosch J, Dagenais GR et al. [Origin Trial Investigators]. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367(4): 319–328. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1203858>.
9. Halperin F, Lopez X, Manning R et al. Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans. Diabetes 2012; 61(2): 301–309. Dostupné z DOI: <http://dx.doi.org/10.2337/db11–1067>.
10. Hanefeld M, Bramlage P. Insulin use early in the course of type 2 diabetes mellitus: the ORIGIN trial. Curr Diab Rep 2013; 13(3): 342–349. Dostupné z DOI: <http://dx.doi.org/10.1007/s11892–013–0366-z>.
11. Harrison LB1, Adams-Huet B, Raskin P et al. b-cell function preservation after 3,5 years of intensive diabetes therapy. Diabetes Care 2012; 35(7): 1406–1412. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11–2170>.
12. Heise T, Hermanski L, Nosek L et al. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab 2012; 14(9): 859–864. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1463–1326.2012.01627.x>.
13. Holden SE, Jenkins-Jones S, Morgan CLet al. Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer. Diabetes Obes Metab 2015; 17(4): 350–362. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12412>.
14. Horvath K, Jeitler K, Berghold A et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2007; (2): CD005613.
15. Chon S, Oh S, Kim SW et al. The Effect of Early Insulin Therapy on Pancreatic β-Cell Function and Long-Term Glycemic Control in Newly Diagnosed Type 2 Diabetic Patients. Korean J Intern Med 2010; 25(3): 273–281. Dostupné z DOI: <http://dx.doi.org/10.3904/kjim.2010.25.3.273>.
16. Inzucchi ES, Bergenstal RM, Buse JB et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38(1): 140–149. Dostupné z DOI: <http://dx.doi.org/10.2337/dc14–2441>.
17. Hirsch IB. Insulin Analogues. N Engl J Med 2005; 352(2): 174–183. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMra040832>.
18. Jonassen I, Havelund S, Hoeg-Jensen T et al. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res 2012; 29(8): 2104–2114. Dostupné z DOI: <http://dx.doi.org/10.1007/s11095–012–0739-z>.
19. Jones S, Benroubi M, Castell C et al. Characteristics of patients with type 2 diabetes mellitus initiating insulin therapy: baseline data from the INSTIGATE study. Curr Med Res Opin 2009; 25(3): 691–700. Dostupné z DOI: <http://dx.doi.org/10.1185/03007990902739669>.
20. Khunti K, Wolden ML, Thorsted BL et al. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care 2013; 36(11): 3411–3417. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–0331>.
21. King P, Peacock I, Donnelly R. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol 1999; 48(5): 643–648.
22. Lankisch MR, Del Prato S, Dain MP et al. Use of a basal-plus insulin regimen in persons with type 2 diabetes stratified by age and body mass index: A pooled analysis of four clinical trials. Primary Care Diabetes 2016; 10(1): 51–59. Dostupné z DOI: <http://dx.doi.org/10.1016/j.pcd.2015.05.003>.
23. Marso, SP, Daniels GH, Brown-Frandsen K et al. [LEADER Steering. LEADER Trial Investigators]. Liraglutide and ardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375(4): 311–322. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1603827>.
24. Marso, SP, Bain SC, Consoli A et al. [SUSTAIN-6 Investigators]. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375: 1834–1844. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1607141>.
25. Martinka E et al. Výsledky štúdie Insula T2. Diabetes Obezita 2017; (v tlači).
26. Martinka, E, Uličiansky V, Mokáň M et al. Konsenzuálny terapeutický algoritmus pre diabetes mellitus 2. typu. Forum Diab 2016; 5(2): 99–108.
27. McCoy RG, Van Houten HK, Ziegenfuss JY et al. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 2012; 35(9): 1897–1901. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11–2054>.
28. MZSR. Aktuálne znenie indikačných obmedzení pre preskripciu liekov hradených z verejného poistenia. Dostupné z WWW: <http://www.health.gov.sk/Clanok?lieky201605>.
29. Ogawa A, Hayashi A, Kishihara E et al. New Indices for Predicting Glycaemic Variability. PLoS ONE 2012; 7(9): e46517. Dostupné z DOI: http://dx.doi.org/10.1371/journal.pone.0046517>.
30. Owens DR, Bolli GB. Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application. Diabetes Technol Ther 2008; 10(5): 333–349. Dostupné z DOI: <http://dx.doi.org/10.1089/dia.2008.0023>.
31. Pisarchik AN, Pochepen ON, Pisarchyk LA. Increasing Blood Glucose Variability Is a Precursor of Sepsis and Mortality in Burned Patients. PLoS ONE 2012; 7(10): e46582. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0046582>.
32. Ratner RE, Gough SC, Mathieu C et al. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab 2013; 15(2): 175–184. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12032>.
33. Rhoads GG, Kosiborod M, Nesto RW et al. Comparison of incidence of acute myocardial infarction in patients with type 2 diabetes mellitus following initiation of neutral protamine Hagedorn insulin versus insulin glargine. Am J Cardiol 2009; 104(7): 910–916. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjcard.2009.05.030>. Erratum in Am J Cardiol 2010; 106(4): 603.
34. Riddle MC, Rosenstock J, Gerich J et al. [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. Diabetes Care 2003; 26(11): 3080–3086. Dostupné z DOI: <https://doi.org/10.2337/diacare.26.11.3080>.
35. Schernthaner G., Lehmann R., Prázný M et al. Diabetes, Obesity and Metabolism (pripravené k publikovaniu)
36. Gerstein HC, Miller ME, Byington RP et al. [Action to Control Cardiovascular Risk in Diabetes Study Group]. Effect of intensive glucose lowering in patients with type 2 diabetes. N Engl J Med 2008; 358(24): 2545–2559. <http://dx.doi.org/10.1056/NEJMoa0802743>
37. Gerstein HC, Bosch J, Dagenais GR et al. [Origin Trial Investigators] Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia. N Engl J Med 2012; 367(4): 319–328. <http://dx.doi.org/10.1056/NEJMoa1203858>.
38. Weng J, Li Y, Xu W et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 2008; 371(9626): 1753–1760. <http://dx.doi.org/10.1016/S0140–6736(08)60762-X>.
39. Yki-Järvinen H, Bergenstal R, Ziemen M et al. (EDITION 2 Study Investigators). New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care 2014; 37(12): 3235–3243. <http://dx.doi.org/10.2337/dc14–0990>.
40. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373(22): 2117–2128. <http://dx.doi.org/10.1056/NEJMoa1504720>.
41. Zinman B. Newer insulin analogs: advances in basal insulin replacement. Diabetes Obes Metab 2013; 15(Suppl 1): 6–10. <http://dx.doi.org/10.1111/dom.12068>.
Štítky
Diabetology Endocrinology Internal medicineČlánok vyšiel v časopise
Forum Diabetologicum
2017 Číslo 2
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