Download PDF
Diabetes aktuell 2017; 15(02): 58-64
DOI: 10.1055/s-0043-105377
Schwerpunkt / Sulfonylharnstoffe
© Georg Thieme Verlag Stuttgart · New York

Sulfonylharnstoffe – warum immer noch im Einsatz?

Widersprüchliche Datenlage erlaubt keine klare Aussage zur Sicherheit
Thomas Forst
1   Profil Mainz
› Author Affiliations
Further Information

Publication History

Publication Date:
24 April 2017 (online)

Also available at
    Permissions and Reprints

Insgesamt stellt sich die Datenlage rund um die kardiovaskuläre Sicherheit der Therapie mit Sulfonylharnstoffen ausgesprochen widersprüchlich dar. Insbesondere die Diskrepanz zwischen den Daten aus randomisierten klinischen und populationsbasierten Studien machen es derzeit unmöglich, die Sicherheit dieser Therapieoption abschließend zu beurteilen. Die bisher vorliegenden Daten sind erheblichen Limitationen unterworfen und können keine ausreichende Evidenz für die Sicherheit einer Sulfonylharnstofftherapie bieten. Ein klareres Bild wird sich hoffentlich mit den Ergebnissen derzeit laufender, randomisierter klinischer Studien ergeben. Bis diese Daten vorliegen, sollte der Einsatz von Sulfonylharnstoffen jedoch kritisch erfolgen. Mit Blick auf die zwischenzeitlich verfügbaren, kardiovaskulär nachweislich sicheren therapeutischen Alternativen fällt eine medizinische Begründung für den Einsatz von Sulfonylharnstoffen immer schwerer.

Key words

urinary tract infection - diabetes mellitus - acute uncomplicated cystitis - acute uncomplicated pyelonephritis - complicated urinary tract infection - uropathogenic Escherichia coli (UPEC)
 

  • Literatur

  • 1 DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care 2013; 36: S127-S138
    CrossrefGoogle Scholar
  • 2 Kahn SE, Haffner SM, Heise MA et al Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427-2443
    CrossrefPubMedGoogle Scholar
  • 3 Corrao G, Romio SA, Zambon A et al Multiple outcomes associated with the use of metformin and sulphonylureas in type 2 diabetes: a population-based cohort study in Italy. Eur J Clin Pharmacol 2011; 67: 289-299
    CrossrefGoogle Scholar
  • 4 Home PD, Pocock SJ, Beck-Nielsen H et al Rosiglitazone evaluated for cardiovascular outcomes in oral agent combi-nation therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009; 373: 2125-2135
    CrossrefGoogle Scholar
  • 5 Mellbin LG, Malmberg K, Norhammar A et al The impact of glucose lowering treatment on long-term prognosis in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI 2 trial. Eur Heart J 2008; 29: 166-176
    Google Scholar
  • 6 Inoguchi T, Umeda F, Kakimoto M et al Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. Endocr J 2000; 47: 763-770
    CrossrefGoogle Scholar
  • 7 Forst T, Dworak M, Berndt-Zipfel C et al Effect of vildagliptin compared to glimepiride on postprandial proinsulin processing in the beta cell of patients with type 2 diabetes mellitus. Diabetes Obes Metab 2013; 15: 576-579
    CrossrefGoogle Scholar
  • 8 Maedler K, Carr RD, Bosco D et al Sulfonylurea induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab 2005; 90: 501-506
    CrossrefGoogle Scholar
  • 9 Meinert CL, Knatterud GL, Prout TE, Klimt CR. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes 1970; 19 (Suppl) 830
    Google Scholar
  • 10 [No authors listed] 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: 837-853
    CrossrefGoogle Scholar
  • 11 Krall RL. Cardiovascular safety of rosiglitazone. Lancet 2007; 369: 1995-1996
    CrossrefGoogle Scholar
  • 12 Hemmingsen B, Schroll JB, Wetterslev J et al Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes: a Cochrane systematic review and meta-analysis of randomized clinical trials and trial sequential analysis. CMAJ Open 2014; 2: E162-E175
    CrossrefPubMedGoogle Scholar
  • 13 Rados DV, Pinto LC, Remonti LR et al The association between sulfonylurea use and all-cause and cardiovascular mortality: a meta-analysis with trial sequential analysis of randomized clinical trials. PLoS Med 2016; 13: e1002091
    CrossrefPubMedGoogle Scholar
  • 14 Palmer SC, Mavridis D, Nicolucci A et al Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA 2016; 316: 313-324
    CrossrefGoogle Scholar
  • 15 Bain S, Druyts E, Balijepalli C et al Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: a Bayesian meta-analysis of survival data. Diabetes Obes Metab 2017; 19: 329-335
    CrossrefPubMedGoogle Scholar
  • 16 Evans JM, Ogston SA, Emslie-Smith A, Morris AD. Risk of morta-lity and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metfor-min. Int J Obes Relat Metab Disord 2006; 49: 930-936
    Google Scholar
  • 17 Rao AD, Kuhadiya N, Reynolds K, Fonseca VA. Is the combination of sulfonylureas and metformin associated with an increased risk of cardiovascular disease or all-cause mortality? A meta-analysis of observational studies. Diabetes Care 2008; 31: 1672-1678
    CrossrefPubMedGoogle Scholar
  • 18 Tzoulaki I, Molokhia M, Curcin V et al Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ 2009; 339: b4731
    CrossrefPubMedGoogle Scholar
  • 19 Morgan CL, Poole CD, Evans M et al What next after metformin? A retrospective evaluation of the outcome of second-line, glucose-lowering therapies in people with type 2 diabetes. J Clin Endocrinol Metab 2012; 97: 4605-4612
    CrossrefGoogle Scholar
  • 20 Pantalone KM, Kattan MW, Yu C et al Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: a retrospective analysis. Diabetes Obes Metab 2012; 14: 803-809
    CrossrefGoogle Scholar
  • 21 Phung OJ, Schwartzman E, Allen RW et al Sulphonylureas and risk of cardiovascular disease: systematic review and meta-analysis. Diabet Med 2013; 30: 1160-1171
    CrossrefGoogle Scholar
  • 22 Monami M, Genovese S, Mannucci E. Cardiovascular safety of sulfonylureas: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013; 15: 938-953
    CrossrefGoogle Scholar
  • 23 Currie CJ, Poole CD, Evans M et al Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. J Clin Endocrinol Metab 2013; 98: 668-677
    CrossrefPubMedGoogle Scholar
  • 24 Wheeler S, Moore K, Forsberg CW et al Mortality among veterans with type 2 diabetes initiating metformin, sulfonylurea or rosiglitazone monotherapy. Int J Obes Relat Metab Disord 2013; 56: 1934-1943
    Google Scholar
  • 25 Mogensen UM, Andersson C, Fosbol EL et al Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus - a retrospective nationwide study. Diabetes Obes Metab 2014; 16: 1001-1008
    CrossrefGoogle Scholar
  • 26 Li Y, Hu Y, Ley SH et al Sulfonylurea use and incident cardiovascular disease among patients with type 2 diabetes: prospective cohort study among women. Diabetes Care 2014; 37: 3106-3113
    CrossrefGoogle Scholar
  • 27 Ke C, Morgan S, Smolina K et al Mortality and cardiovascular risk of sulfonylureas in south asian, chinese and other canadians with diabetes. Can J Diabetes. 21.10.2016 pii: S1499-2671(16)30106-X [Epub ahead of print]
    Google Scholar
  • 28 Forst T, Hanefeld M, Jacob S et al Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Diab Vasc Dis Res 2013; 10: 302-314
    CrossrefPubMedGoogle Scholar
  • 29 Gallwitz B, Rosenstock J, Rauch T et al 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012; 380: 475-483
    CrossrefGoogle Scholar
  • 30 Gamble JM, Thomas JM, Twells LK et al Comparative effectiveness of incretin-based therapies and the risk of death and cardiovascular events in 38,233 metformin monotherapy users. Medicine (Baltimore) 2016; 95: e3995
    CrossrefGoogle Scholar
  • 31 Eriksson JW, Bodegard J, Nathanson D et al Sulphonylurea compared to DPP-4 inhibitors in combination with metformin carries increased risk of severe hypoglycemia, cardiovascular events, and all-cause mortality. Diabetes Res Clin Pract 2016; 117: 39-47
    CrossrefGoogle Scholar
  • 32 Morgan CL, Mukherjee J, Jenkins-Jones S et al Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. Diabetes Obes Metab 2014; 16: 977-983
    CrossrefGoogle Scholar
  • 33 Zinman B, Wanner C, Lachin JM et al Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-2128
    CrossrefGoogle Scholar
  • 34 Marso SP, Daniels GH, Brown-Frandsen K et al Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375: 311-322
    CrossrefGoogle Scholar
  • 35 Forst T, Anastassiadis E, Diessel S et al Effect of linagliptin compared to glimepiride on postprandial glucose metabolism, islet cell function, and vascular function parameters in patients with type 2 diabetes mellitus on ongoing metformin treatment. Diabetes Metab Res Rev 2014; 30: 582-589
    CrossrefGoogle Scholar
  • 36 Malaguarnera R, Sacco A, Voci C et al Proinsulin binds with high affinity the insulin receptor isoform A and predominantly activates the mitogenic pathway. Endocrinology 2012; 153: 2152-2163
    CrossrefGoogle Scholar
  • 37 Lindahl B, Dinesen B, Eliasson M et al High proinsulin concentration precedes acute myocardial infarction in a nondiabetic population. Metabolism 1999; 48: 1197-1202
    CrossrefGoogle Scholar
  • 38 Zethelius B, Lithell H, Hales CN, Berne C. Insulin sensitivity, proinsulin and insulin as predictors of coronary heart disease. A population-based 10-year, follow-up study in 70-year old men using the euglycaemic insulin clamp. Int J Obes Relat Metab Disord 2005; 48: 862-867
    Google Scholar
  • 39 Burke MA, Mutharasan RK, Ardehali H. The sulfonylurea receptor, an atypical ATP-binding cassette protein, and its regulation of the KATP channel. Circ Res 2008; 102: 164-176
    CrossrefGoogle Scholar
  • 40 Abdelmoneim AS, Welsh RC, Eurich DT, Simpson SH. Sulfonylurea use is associated with larger infarct size in patients with diabetes and ST-elevation myocardial infarction. Int J Cardiol 2016; 202: 126-130
    CrossrefGoogle Scholar
  • 41 Monami M, Lamanna C, Pala L et al Treatment with insulin secretagogues and cancer-related mortality in type 2 diabetic patients a retrospective cohort study. Exp Clin Endocrinol Diabetes 2008; 116: 184-189
    Article in Thieme ConnectGoogle Scholar
  • 42 Singh S, Singh PP, Singh AG et al Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Am J Gastroenterol 2013; 108: 510-519
    CrossrefGoogle Scholar
  • 43 Chang HY, Hsieh CF, Singh S et al Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide retrospective cohort study from Taiwan. Pharmacoepidemiol Drug Saf 2015; 24: 567-575
    CrossrefGoogle Scholar
  • 44 Rosenstock J, Marx N, Kahn SE et al Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CAROLINA trial. Diab Vasc Dis Res 2013; 10: 289-301
    CrossrefGoogle Scholar
  • 45 Nathan DM, Buse JB, Kahn SE et al Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care 2013; 36: 2254-2261
    CrossrefGoogle Scholar