Sulfonylurea derivatives and risk of hypoglycaemia in type 2 diabetic patients

Česká verzia

Authors: Jakub Svěcený ¹; Jana Jirušková ¹; Karel Hrach ²; Lucie Radovnická ¹; Jiří Laštůvka ¹
Authors place of work: Interní oddělení Masarykovy nemocnice v Ústí nad Labem, Krajská zdravotní a. s. ¹; Katedra zdravotnických studií, Univerzita J. E. Purkyně ²
Published in the journal: Vnitř Lék 2020; 66(6): 35-42
Category: Original Contributions

Summary

Hypoglycemia related to treatment of type 2 diabetes mellitus patients constantly represents a substantial problem. It is connected with higher mortality and lower quality of life, mostly displayed with elder patients. Therefore it is vital to revise the antidiabetic therapy regularly and to inquire for the associated risks. Nevertheless, elder patiens are often following the inadvisable treatment by sulphonylureas derivates, which represent the second most risky medication causing hypoglycemia after insulin. In our retrospective study we analysed the occurence of serious hypoglycemia, caused by any factor, with severe diabetics urgently hospitalised at The Department of Internal Medicine of Masaryk Hospital in Ústí nad Labem, in relation to the applied antidiabetic therapy. We suspected a negative influence of hypoglycemizing therapy (above all sulphonylureas) with the elderly patiens. In sum, we hospitalised 32 patients with type 2 diabetes mellitus (average age 76,5 ± 8,2 years), 18 of these using sulphonylureas (average age 77,4, with a relatively wide range from 65 to alarming 93 years). The average figure of estimated glomerular filtration rate (eGFR) was 0,745 (±0,293) ml/s/1,73m2. Moreover, the patients manifested polmorbidity – the average of comorbidities was 3,125, and even 3,5 with patiens on sulphonylureas. Following the arguments summarised above, we believe that hypoglycemic episodes are extremely dangerous especially for elder patients with T2DM, and from this point of view, the medication using sulphonylureas derivates seems to be inappropriate.

Keywords:

sulphonylureas – hypoglycaemia – diabetes mellitus – elderly – antidiabetic therapy

Zdroje

1. Agiostratidou G, Anhalt H, Ball D, Blonde L, Gourgari E, Harriman KN, Kowalski AJ, Madden P, McAuliffe-Fogarty AH, McElwee-Malloy M, Peters A, Raman S, Reifschneider K, Rubin K, Weinzimer SA. Standardizing Clinically Meaningful Outcome Measures Beyond HbA1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange. Diabetes Care. 2017 Dec;40(12):1622-1630. doi: 10.2337/dc17-1624. Review. PubMed PMID: 29162582; PubMed Central PMCID: PMC5864122.

2. Minimizing Hypoglycemia in Diabetes. Diabetes Care. 2015; 38(8): 1583–1591. doi: 10.2337/dc15-0279.

3. Wright AD, Cull CA, Macleod KM, Holman RR. Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73. J Diabetes Complications. 2006; 20(6): 395– 401. doi: 10.1016/j.jdiacomp.2005.08.010.

4. Quilliam BJ, Simeone JC, Ozbay AB. Risk factors for hypoglycemia-related hospitalization in patients with type 2 diabetes: a nested case-control study. Clin Ther. 2011; 33(11): 1781–1791. doi: 10.1016/j.clinthera.2011.09.020.

5. Misra-Hebert AD, Pantalone KM, Ji X, Milinovich A, Dey T, Chagin KM, Bauman JM, Kattan MW, Zimmerman RS. Patient Characteristics Associated With Severe Hypoglycemia in a Type 2 Diabetes Cohort in a Large, Integrated Health Care System From 2006 to 2015. Diabetes Care. 2018; 41(6): 1164–1171. doi: 10.2337/dc17-1834.

6. Davis TM, Brown SG, Jacobs IG, Bulsara M, Bruce DG, Davis WA. Determinants of severe hypoglycemia complicating type 2 diabetes: the Fremantle diabetes study. J Clin Endocrinol Metab. 2010; 95(5): 2240–2247. doi: 10.1210/jc.2009-2828.

7. McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012; 35(9): 1897–1901. doi: 10.2337/dc11-2054.

8. Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal T, Hemmingsen C, Wetterslev J. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ. 2011; 343: d6898. doi: 10.1136/bmj.d6898.

9. Bolek T, Samoš M, Mokáň M, et al. Akútne príčiny náhlých úmrtí u pacientov so závažnou hypoglykemiou. Vnitř Lék 2016; 62(6): 462–466. https://www.prolekare.cz/casopisy/ vnitrni-lekarstvi/2016-6/akutne-priciny-nahlych-umrti-u-pacientov-so-zavaznou-hypoglykemiou-58811

10. Svačina Š, Jurašková B, Karen I, et al. Doporučené postupy v léčbě starších pacientů s diabetes mellitus v ČR. DMEV 2013; 2: 82–92.

11. Hirst JA, Farmer AJ, Dyar A, Lung TW, Stevens RJ. Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis. Diabetologia. 2013; 56(5): 973–984. doi: 10.1007/s00125-013-2856-6.

12. Standards of medical Care in Diabetes“ Introduction. Diabetes Care. 2011, 34. (Suppl 1): S1–2., doi: 10.2337/dc11-S001.

13. Standards of mediacal care in diabetes--2015. Diabetes Care. 2015 Jan;38 Suppl:S1-2. doi: 10.2337/dc15-S001.

14. Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, D‘Alessio DA, Davies MJ. 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(2): 487–493. doi: 10.2337/dci19-0066.

15. Davies MJ, D‘Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018 Dec;61(12):2461-2498. doi: 10.1007/s00125-018-4729-5.

16. Ústav zdravotnických informací a statistiky ČR. (2019). Zdravotnická ročenka České republiky 2017. Retrieved November 5, 2019, from http://www.uzis.cz/katalog/rocenky/zdravotnicka-rocenka-ceske-republiky-1961-az-2013.

17. Kitten AK, Kamath M, Ryan L, Reveles KR. National ambulatory care non-insulin antidiabetic medication prescribing trends in the United States from 2009 to 2015. PLoS One. 2019; 14(8): e0221174. doi: 10.1371/journal.pone.0221174.

18. Khunti K, Chatterjee S, Gerstein HC, Zoungas S, Davies MJ. Do sulphonylureas still have a place in clinical practice?. Lancet Diabetes Endocrinol. 2018 Oct;6(10):821-832. doi: 10.1016/S2213-8587(18)30025-1.

19. Chan SP, Colagiuri S. Systematic review and meta-analysis of the efficacy and hypoglycemic safety of gliclazide versus other insulinotropic agents. Diabetes Res Clin Pract. 2015; 110(1): 75–81. doi: 10.1016/j.diabres.2015.07.002.

20. Ahrén B. Are sulfonylureas less desirable than DPP-4 inhibitors as add-on to metformin in the treatment of type 2 diabetes?. Curr Diab Rep. 2011; 11(2): 83–90. doi: 10.1007/ s11892-011-0179-x.

21. Penfornis A, Bourdel-Marchasson I, Quere S, Dejager S. Real-life comparison of DPP4-inhibitors with conventional oral antidiabetics as add-on therapy to metformin in elderly patients with type 2 diabetes: the HYPOCRAS study. Diabetes Metab. 2012; 38(6): 550–557. doi: 10.1016/j.diabet.2012.08.003.

22. Curkendall SM, Zhang B, Lenhart G, Thomson E, Bell KF. Rate of hypoglycemia in patients with type 2 diabetes receiving metformin plus saxagliptin versus metformin plus sulfonylurea: a retrospective observational cohort study using administrative claims data. Expert Rev Endocrinol Metab. 2014; 9(2): 183–191. doi: 10.1586/17446651.2014.870471.

23. Detournay B, Halimi S, Robert J, Deschaseaux C, Dejager S. Hypoglycemia hospitalization frequency in patients with type 2 diabetes mellitus: a comparison of dipeptidyl peptidase 4 inhibitors and insulin secretagogues using the French health insurance database. Vasc Health Risk Manag. 2015; 11: 417–425. doi: 10.2147/VHRM.S84507.

24. Wu S, Chai S, Yang J, Cai T, Xu Y, Yang Z, Zhang Y, Ji L, Sun F, Zhan S. Gastrointestinal Adverse Events of Dipeptidyl Peptidase 4 Inhibitors in Type 2 Diabetes: A Systematic Review and Network Meta-analysis. Clin Ther. 2017 Sep;39(9):1780-1789.e33. doi: 10.1016/j. clinthera.2017.07.036.

25. Salvo F, Moore N, Arnaud M, Robinson P, Raschi E, De Ponti F, Bégaud B, Pariente A. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. BMJ. 2016; 353: i2231. doi: 10.1136/bmj.i2231.

26. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009; 301(15): 1565–1572. doi: 10.1001/jama.2009.460.

27. Bramlage P, Gitt AK, Binz C, Krekler M, Deeg E, Tschöpe D. Oral antidiabetic treatment in type-2 diabetes in the elderly: balancing the need for glucose control and the risk of hypoglycemia. Cardiovasc Diabetol. 2012; 11: 122. doi: 10.1186/1475-2840-11-122.

28. Bremer JP, Jauch-Chara K, Hallschmid M, Schmid S, Schultes B. Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care. 2009; 32(8): 1513–1517. doi: 10.2337/dc09-0114.

29. Vimalananda VG, DeSotto K, Chen T, Mullakary J, Schlosser J, Archambeault C, Peck J, Cassidy H, Conlin PR, Evans S, McConnell M, Shirley E. A Quality Improvement Program to Reduce Potential Overtreatment of Diabetes Among Veterans at High Risk of Hypoglycemia. Diabetes Spectr. 2017; 30(3): 211–216. doi: 10.2337/ds16-0006.

30. Liatis S, Mylona M, Kalopita S, Papazafiropoulou A, Karamagkiolis S, Melidonis A, Xilomenos A, Ioannidis I, Kaltsas G, Lanaras L, Papas S, Basagiannis C, Kokkinos A. Hypoglycaemia requiring medical assistance in patients with diabetes: a prospective multicentre survey in tertiary hospitals. Diabetes Metab. 2015; 41(2): 126–131. doi: 10.1016/j. diabet.2014.10.006.

31. Breuer HW, Ptak P. (Hypoglycemia – frequency, causes, induced costs). Dtsch Med Wochenschr. 2012; 137(19): 988–992. doi: 10.1055/s-0031-1299014.

32. Nelson JM, Dufraux K, Cook PF. The relationship between glycemic control and falls in older adults. J Am Geriatr Soc. 2007; 55(12): 2041–2044. doi: 10.1111/j.1532-5415.2007.01430.x.

33. Fulcher G, Singer J, Castañeda R, Fraige Filho F, Maffei L, Snyman J, Brod M. The psychosocial and financial impact of non-severe hypoglycemic events on people with diabetes: two international surveys. J Med Econ. 2014; 17(10): 751–761. doi: 10.3111/13696998.2014.946992.

34. Parekh TM, Raji M, Lin YL, Tan A, Kuo YF, Goodwin JS. Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas. JAMA Intern Med. 2014; 174(10): 1605–1612. doi: 10.1001/jamainternmed.2014.3293.

35. Clayton D, Woo V, Yale JF. Hypoglycemia. Can J Diabetes. 2013; 37 Suppl 1: S69–71. doi: 10.1016/j.jcjd.2013.01.022.

36. Stahn A, Pistrosch F, Ganz X, Teige M, Koehler C, Bornstein S, Hanefeld M. Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases: silent hypoglycemias and silent arrhythmias. Diabetes Care. 2014; 37(2): 516–520. doi: 10.2337/dc13-0600.

37. Bron M, Marynchenko M, Yang H, Yu AP, Wu EQ. Hypoglycemia, treatment discontinuation, and costs in patients with type 2 diabetes mellitus on oral antidiabetic drugs. Postgrad Med. 2012; 124(1): 124–132. doi: 10.3810/pgm.2012.01.2525.

38. Majumdar SR, Hemmelgarn BR, Lin M, McBrien K, Manns BJ, Tonelli M. Hypoglycemia associated with hospitalization and adverse events in older people: population-based cohort study. Diabetes Care. 2013; 36(11): 3585–3590. doi: 10.2337/dc13-0523.

39. Nordin C. The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidence. Diabetologia. 2010; 53(8): 1552–1561. doi: 10.1007/s00125-010-1752-6.

40. Holstein A, Hammer C, Hahn M, Kulamadayil NS, Kovacs P. Severe sulfonylurea-induced hypoglycemia: a problem of uncritical prescription and deficiencies of diabetes care in geriatric patients. Expert Opin Drug Saf. 2010; 9(5): 675–681. doi: 10.1517/14740338.2010.492777.

41. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358(24): 2545–2559. doi: 10.1056/NEJMoa0802743.

42. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358(24): 2560–2572. doi: 10.1056/NEJMoa0802987.

43. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009; 360(2): 129–139. doi: 10.1056/NEJMoa0808431.

44. Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007; 369(9557): 201–207. doi: 10.1016/S01406736(07)60108-1.

45. Moen MF, Zhan M, Hsu VD, Walker LD, Einhorn LM, Seliger SL, Fink JC. Frequency of hypoglycemia and its significance in chronic kidney disease. Clin J Am Soc Nephrol. 2009; 4(6): 1121–1127. doi: 10.2215/CJN.00800209.

46. Ústav zdravotnických informací a statistiky ČR. (2019). Zdravotnická ročenka České republiky 2011. Retrieved November 5, 2019, from http://www.uzis.cz/katalog/rocenky/zdravotnicka-rocenka-ceske-republiky-1961-az-2013.

47. Ústav zdravotnických informací a statistiky ČR. (2019). Zdravotnická ročenka České republiky 2015. Retrieved November 5, 2019, from http://www.uzis.cz/katalog/rocenky/ zdravotnicka-rocenka-ceske-republiky-1961-az-2013.