Diyabetin Farmakolojik Tedavisinde Güncel Yaklaşımlar
Özet
Diyabet tedavisindeki güncel farmakolojik yaklaşımlar, hastalığın ilerleyici kronik doğası ve küresel artışı nedeniyle bireyselleştirilmiş stratejilere dayanmaktadır. Tip 1 diyabet yönetiminde, açlık ve tokluk kan şekerini düzenleyen bazal-bolus insülin rejimleri ile hızlı etkili insülin analogları, hipoglisemi riskini ve kilo alımını azaltmaları sebebiyle öncelikli olarak tercih edilmektedir. İnsülin pompaları ve pramlintid gibi ek tedaviler de glisemi kontrolünü optimize etmeye yardımcı olmaktadır. Tip 2 diyabet tedavisinde ise yaşam tarzı değişiklikleri ve güçlü, düşük maliyetli bir ajan olan metformin birinci basamak tedavisinin temelini oluşturmaktadır. Ancak, hastada aterosklerotik kalp hastalığı, kalp yetmezliği veya kronik böbrek yetmezliği gibi komorbiditelerin varlığı durumunda, hemoglobin A1C seviyesinden bağımsız olarak kardiyovasküler ve renal koruma sağlayan GLP-1 analogları ile SGLT-2 inhibitörlerinin kullanımı erken dönemde önerilmektedir. Glisemik hedeflere ulaşılamayan ilerleyici tablolarda veya şiddetli hiperglisemi semptomlarında insülin tedavisine geçiş geciktirilmemelidir. Özetle, modern diyabet kılavuzları; ilaçların etkinliği, yan etkileri, maliyeti ve hastanın kardiyorenal risk profilini birlikte değerlendiren hasta merkezli bütünsel bir yaklaşımı benimsemektedir.
Current pharmacological approaches in diabetes treatment are based on individualized strategies due to the progressive chronic nature and global increase of the disease. In type 1 diabetes management, basal-bolus insulin regimens and rapid-acting insulin analogs, which regulate fasting and postprandial blood glucose, are primarily preferred because they reduce the risk of hypoglycemia and weight gain. Insulin pumps and adjunctive therapies like pramlintide also help optimize glycemic control. For type 2 diabetes treatment, lifestyle modifications and metformin, a potent and low-cost agent, form the cornerstone of first-line therapy. However, in the presence of comorbidities such as atherosclerotic heart disease, heart failure, or chronic kidney disease, the use of GLP-1 analogs and SGLT-2 inhibitors, which provide cardiovascular and renal protection, is recommended early, regardless of hemoglobin A1C levels. In progressive cases where glycemic goals are not achieved or in severe hyperglycemic symptoms, the transition to insulin therapy should not be delayed. In summary, modern diabetes guidelines adopt a patient-centered holistic approach that evaluates drug efficacy, side effects, cost, and the patient's cardiorenal risk profile together.
Referanslar
Karuranga, S., Rocha Fernandes, J., Huang, Y., Malanda, B. (2017), International Diabetes Federation Diabetes Atlas, 8th Edition, (a) Chapter 1, What is diabetes? 16; (b) Chapter 3, Global picture, 40-41.
Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Res Clin Pract. 2019;157 :107843. [Crossref]
American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45:S125.
Holt RIG, DeVries JH, Hess-Fischl A, et al. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2021;44:2589–2625
Tricco AC, Ashoor HM, Antony J, et al. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis. BMJ 2014;349:g5459
Bartley PC, Bogoev M, Larsen J, Philotheou A. Long-term efficacy and safety of insulin detemir compared to Neutral Protamine Hagedorn insulin in patients with Type 1 diabetes using a treat-totarget basal-bolus regimen with insulin aspart at meals: a 2-year, randomized, controlled trial. Diabet Med 2008;25:442–449
DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA 2003;289:2254–2264
Russell-Jones D, Bode BW, De Block C, et al. Fast-acting insulin aspart improves glycemic control in basal-bolus treatment for type 1 diabetes: results of a 26-week multicenter, active-controlled, treat-to-target, randomized, parallel-group trial (onset 1). Diabetes Care 2017;40:943–950
Klaff L, Cao D, Dellva MA, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: results from the 26-week PRONTOT1D study. Diabetes Obes Metab 2020;22: 1799–1807
Blevins T, Zhang Q, Frias JP, Jinnouchi H; PRONTO-T2D Investigators. Randomized doubleblind clinical trial comparing ultra rapid lispro with lispro in a basal-bolus regimen in patients with type 2 diabetes: PRONTO-T2D. Diabetes Care 2020;43:2991–2998
Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB; Affinity 1 Study Group. Inhaled technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Diabetes Care 2015;38:2266–2273 10. Russell-Jones D, B
Lane W, Bailey TS, Gerety G, et al.; Group Information; SWITCH 1. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 1 diabetes: the SWITCH 1 randomized clinical trial. JAMA 2017;318:33–44
Home PD, Bergenstal RM, Bolli GB, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 1 diabetes: a randomized, phase 3a, open-label clinical trial (EDITION 4). Diabetes Care 2015;38:2217–2225
Türkiye Endokrinoloji ve Metabolizma Derneği Diabetes Mellitus ve Komplikasyonlarının Tanı, Tedavi ve İzlem Kılavuzu-2020
Pickup JC. The evidence base for diabetes technology: appropriate and inappropriate metaanalysis. J Diabetes Sci Technol 2013;7: 1567–1574
Bergenstal RM, Klonoff DC, Garg SK, et al.; ASPIRE In-Home Study Group. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med 2013;369:224–232
Buckingham BA, Raghinaru D, Cameron F, et al.; In Home Closed Loop Study Group. Predictive low-glucose insulin suspension reduces duration of nocturnal hypoglycemia in children without increasing ketosis. Diabetes Care 2015;38:1197–1204
Bell KJ, Smart CE, Steil GM, Brand-Miller JC, King B, Wolpert HA. Impact of fat, protein, and glycemic index on postprandial glucose control in type 1 diabetes: implications for intensive diabetes management in the continuous glucose monitoring era. Diabetes Care 2015;38:1008–1015
Whitehouse F, Kruger DF, Fineman M, et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care 2002;25:724–7303
Ratner RE, Want LL, Fineman MS, et al. Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes. Diabetes Technol Ther 2002;4:51–61
Hollander PA, Levy P, Fineman MS, et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 2003;26:784–790
Ratner RE, Dickey R, Fineman M, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med 2004;21:1204–1212
Meng H, Zhang A, Liang Y, Hao J, Zhang X, Lu J. Effect of metformin on glycaemic control in patients with type 1 diabetes: a meta-analysis of randomized controlled trials. Diabetes Metab Res Rev 2018;34:e2983
Petrie JR, Chaturvedi N, Ford I, et al.; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2017;5:597–609
Dean PG, Kukla A, Stegall MD, Kudva YC. Pancreas transplantation. BMJ 2017;357:j1321
Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669–2701
Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020;43:487–493
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–1589
U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. Accessed 20 October 2021. Available from https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-warnings-regarding-use-diabetes-medicine-metformin –certain
Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375:1834.
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375:311
Mann JFE, Ørsted DD, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377:839
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019; 394:121.
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet 2019; 394:131.
Kanie T, Mizuno A, Takaoka Y, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 10:CD013650.
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020; 383:1436.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380:347.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373:2117.
NeNeal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377:644.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med 2019; 380:2295.
Shyangdan DS, Royle P, Clar C, et al. Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev 2011; :CD006423.
Singh S, Wright EE Jr, Kwan AY, et al. Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab 2017; 19:228.
American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45:S125.
Davies MJ, D'Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41:2669.
Buse JB, Wexler DJ, Tsapas A, et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020; 43:487.
Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care 2012; 35:2650.
Rubino F, Nathan DM, Eckel RH, et al. Metabolic Surgery in Type 2 Diabetes Treatment Algorithm: Joint Statement from International Diabetes Organizations. Diabetes Care 2016; 39:861.
American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, et al. 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45:S113.
Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ 2009;180:385–397
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
Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract 2008;81:184–189
Owens DR, Traylor L, Mullins P, Landgraf W. Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analyzed according to concomitant oral antidiabetes therapy. Diabetes Res Clin Pract 2017;124(Suppl. C):57–65
Riddle MC, Rosenstock 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. Diabetes Care 2003;26:3080–3086
Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose- lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care 2006;29:1269–1274
