Diabetologie und Stoffwechsel 2019; 14(S 02): S167-S187
DOI: 10.1055/a-0898-9617
DDG-Praxisempfehlung
© Georg Thieme Verlag KG Stuttgart · New York

Therapie des Typ-2-Diabetes

Rüdiger Landgraf
1   Deutsche Diabetes Stiftung, München
,
Jens Aberle
2   Sektion Endokrinologie und Diabetologie, Universitäres Adipositas-Zentrum Hamburg, Universitätsklinikum Hamburg-Eppendorf
,
Andreas L. Birkenfeld
3   Universitätsklinikum Carl Gustav Carus an der TU Dresden, Bereich Metabolisch Vaskuläre Medizin, Dresden und Deutsches Zentrum für Diabetesforschung (DZD e. V.), Neuherberg
4   Medizinische Klinik IV, Universitätsklinikum Tübingen
,
Baptist Gallwitz
4   Medizinische Klinik IV, Universitätsklinikum Tübingen
,
Monika Kellerer
5   Zentrum für Innere Medizin I, Marienhospital Stuttgart
,
Harald Klein
6   Medizinische Klinik I, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum
,
Dirk Müller-Wieland
7   Medizinische Klinik I, Universitätsklinikum RWTH Aachen, Aachen
,
Michael A. Nauck
8   Diabeteszentrum Bochum-Hattingen, St.-Josef-Hospital, Ruhr-Universität, Bochum
,
Hans-Martin Reuter
9   Diabetologische Schwerpunktpraxis, Jena
,
Erhard Siegel
10   Abteilung für Innere Medizin – Gastroenterologie, Diabetologie/Endokrinologie und Ernährungsmedizin, St. Josefkrankenhaus Heidelberg GmbH, Heidelberg
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
29. Oktober 2019 (online)

Die Praxisempfehlungen der Deutschen Diabetes Gesellschaft (DDG) zusammen mit der Deutschen Gesellschaft für Innere Medizin (DGIM) lehnen sich an die Inhalte der Nationalen Versorgungsleitlinie (NVL) „Therapie des Typ-2-Diabetes“ an [1]. Die in den vorliegenden Praxisempfehlungen der DDG erfolgten Modifikationen in der Therapie und dessen Begründungen wurden auf der Basis neuer randomisierter kontrollierter Studien (RCTs) und Metaanalysen aktualisiert und von der DDG und der DGIM konsentiert.

 
  • Literatur

  • 1 Nationale Versorgungsleitlinien. www.versorgungsleitlinien.de
  • 2 Alberti KGMM, Eckel RH, Grundy SM. et al. Harmonizing the Metabolic Syndrome. Circulation 2009; 120: 1640-1645
  • 3 Heinemann L, Kaiser P, Freckmann G. et al. HbA1c-Messung in Deutschland: Ist die Qualität ausreichend für Verlaufskontrolle und Diagnose?. Diabetologie 2018; 13: 46-53
  • 4 Petersmann A, Müller-Wieland D, Müller UA. et al. Definition, Klassifikation und Diagnostik des Diabetes mellitus. Diabetolgie 2019; 14 (Suppl. 02) S111-S117
  • 5 Landgraf R, Nauck M, Freckmann G. et al. Fallstricke bei der Diabetesdiagnostik: Wird zu lax mit Laborwerten umgegangen?. Dtsch Med Wochenschr 2018; 143: 1549-1555
  • 6 Nationale VersorgungsLeitlinie (NVL) Diabetes – Strukturierte Schulungsprogramme. 2018 www.leitlinien.de/nvl/diabetes/schulungsprogramme
  • 7 Wang R, Song Y, Yan Y. et al. Elevated serum uric acid and risk of cardiovascular or all-cause mortality in people with suspected or definite coronary artery disease: A meta-analysis. Atherosclerosis 2016; 254: 193-199
  • 8 Praxisempfehlungen DDG zu Lipidtherapie, Diabetologie 2019.
  • 9 The Task Force for the management of arterial hypertension of the European Society of cardiology (ESC) and the European Society of Hypertension (ESH). 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021-3104
  • 10 Forouhi NG, Misra A, Mohan V. et al. Dietary and nutritional approaches for prevention and management of type 2 diabetes. BMJ 2018; 361: k2234
  • 11 Serra-Majem L, Román-Viñas B, Sanchez-Villegas A. et al. Benefits of the Mediterranean diet: Epidemiological and molecular aspects. Mol Aspects Med 2019; 67: 1-55
  • 12 Taylor R, Al-Mrabeh A, Sattar N. Understanding the mechanisms of reversal of type 2 diabetes. Lancet Diabetes Endocrinol 2019; DOI: S2213-8587(19)30076-2.
  • 13 Evert AB, Dennison M, Gardner CD. et al. Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report. Diabetes Care 2019; 42 (05) 731-754
  • 14 Kempf K, Altpeter B, Berger J. et al. Efficacy of the telemedical lifestyle intervention program TeLiPro in advanced stages of type 2 diabetes: A randomized controlled trial. Diabetes Care 2017; 40 (07) 863-871
  • 15 Lean MEJ, Leslie WS, Barnes AC. et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, clusterrandomised trial. Lancet 2018; 391: 541-551
  • 16 Adipositas – Prävention und Therapie. AWMF Register Nr. 050-001.
  • 17 Lawall H, Huppert P, Rümenapf G. et al. Periphere arterielle Verschlusskrankheit (PAVK), Diagnostik, Therapie und Nachsorge. AWMF Register Nr. 065-003 2015.
  • 18 Nationale VersorgungsLeitlinie Neuropathie bei Diabetes im Erwachsenenalter. 2016 www.leitlinien.de/mdb/downloads/nvl/diabetes-mellitus/dm-neuropathie
  • 19 Nationale VersorgungsLeitlinie Prävention und Therapie von Netzhautkomplikationen bei Diabetes. 2016 www.leitlinien.de/nvl/html/netz.hautkomplikationen
  • 20 Nationale VersorgungsLeitlinie (NVL) Typ-2-Diabetes Präventions- und Behandlungsstrategien für Fußkomplikationen. 2018 www.leitlinien.de/nvl/diabetes/fusskomplikationen
  • 21 Roeb E, Steffen HM, Bantel H. et al. S2k Leitlinie: Nicht-alkoholische Fettlebererkrankungen. AWMF Register Nr. 021-025 2015.
  • 22 Nationale VersorgungsLeitlinie Nierenerkrankungen bei Diabetes im Erwachsenenalter. 2018 www.leitlinien.de/nvl/diabetes/nierenerkrankungen
  • 23 Nationale VersorgungsLeitlinie Chronische Herzinsuffizienz. 2018 https://www.leitlinien.de/nvl/html/nvl-chronische-herzinsuffizienz
  • 24 Nationale Versorgungs-Leitlinie Chronische Koronare Herzerkrankung (KHK). 2016 https://www.leitlinien.de/mdb/downloads/nvl/khk/ , www.leitlinien.de/nvl/html/nvl-chronische-khk
  • 25 Piercy KL, Richard P, Troiano RP. et al. The Physical Activity Guidelines for Americans. JAMA 2018; 320 (19) 2020-2028
  • 26 The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369: 145-154
  • 27 Unick JL, Gaussoin SA, Hill JO. et al. Objectively assessed physical activity and weight loss maintenance among individuals enrolled in a lifestyle intervention. Obesity (Silver Spring) 2017; 25 (11) 1903-1909
  • 28 The Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomized clinical trial. Lancet Diabetes Endocrinol 2016; 4: 913-921
  • 29 Gregg EW, Lin J, Bardenheier B. et al. Impact of Intensive Lifestyle Intervention on Disability-Free Life Expectancy: The LookAHEAD Study. Diabetes Care 2018; 41: 1040-1048
  • 30 Yang D, Yang Y, Li Y. et al. Physical Exercise as Therapy for Type 2 Diabetes Mellitus: From Mechanism to Orientation. Ann Nutr Metab 2019; 74 (04) 313-321
  • 31 Tarp J, Støle AP, Blond K. et al. Cardiorespiratory fitness, muscular strength and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetologia 2019; 62: 1129-1142
  • 32 Liu Y, Ye W, Chen Q. et al. Resistance Exercise Intensity is Correlated with Attenuation of HbA1c and Insulin in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health 2019; 16 (01) E140
  • 33 Pan A, Yeli Wang Y, Talaei M. et al. Relation of active, passive, and quitting smoking with incident diabetes: a meta-analysis and systematic review. Lancet Diabetes Endocrinol 2015; 3 (12) 958-996
  • 34 www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RV_STP/m-r/metformin.html
  • 35 Lazarus B, Wu A, Shin JI. et al. Association of metformin use with risk of lactic acidosis across the range of kidney function. A community-based cohort tudy. JAMA Intern Med 2018; 178 (07) 903-910
  • 36 Griffin SJ, Leaver JK, Irving GJ. et al. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trails among people with type 2 diabetes. Diabetologia 2017; 60: 1620-1629
  • 37 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 (03) 313-324
  • 38 Madsen KS, Kähler P, Kähler LKA. et al. Metformin and second- or third-generation sulphonylurea combination therapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev 2019; 4: CD012368
  • 39 Mallik R, Chowdhury TA. Metformin in cancer. Diabetes Res Clin Pract 2018; 143: 409-419
  • 40 Thakur S, Daley B, Klubo-Gwiezdzinska J. The role of the antidiabetic drug metformin in the treatment of endocrine tumors. J Mol Endocrinol 2019; DOI: JME-19-0083.R1.
  • 41 De A, Kuppusamy G. Metformin in breast cancer: preclinical and clinical evidence. Curr Probl Cancer 2019; DOI: S0147-0272(19)30047-9.
  • 42 Rahmani J, Manzari N, Thompson J. et al. The effect of metformin on biomarkers associated with breast cancer outcomes: a systematic review, meta-analysis, and dose-response of randomized clinical trials. Clin Transl Oncol 2019; DOI: 10.1007/s12094-019-02108-9.
  • 43 Fong W, To KKW. Drug repurposing to overcome resistance to various therapies for colorectal cancer. Cell Mol Life Sci 2019; DOI: 10.1007/s00018-019-03134-0.
  • 44 Feng Z, Zhou X, Liu N. et al. Metformin use and prostate cancer risk: A meta-analysis of cohort studies. Medicine (Baltimore) 2019; 98 (12) e14955
  • 45 Marx N, Rosenstock J, Kahn SE. et al. Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA®). Diab Vasc Dis Res 2015; 12 (03) 164-174
  • 46 Rosenstock J, Kahn SE, Johansen OE. et al. on behalf of the CAROLINA Investigators. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA 2019; DOI: 10.1001/jama.2019.13772. . [Epub ahead of print]
  • 47 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 (06) e1002091
  • 48 Azoulay L, Suissa S. Sulfonylureas and the risks of cardiovascular events and death: A methodological meta-regression analysis of the observational studies. Diabetes Care 2017; 40: 706-714
  • 49 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 (03) 329-335
  • 50 Zhuang XD, He X, Yang DY. et al. Comparative cardiovascular outcomes in the era of novel anti-diabetic agents: a comprehensive network metaanalysis of 166371 participants from 170 randomized controlled trials. Cardiovasc Diabetol 2018; 17 (01) 79
  • 51 Powell WR, Christiansen CL, Miller DR. Meta-analysis of sulfonylurea therapy on long-term risk of mortality and cardiovascular events compared to other oral glucose-lowering treatments. Diabetes Ther 2018; 9 (04) 1431-1440
  • 52 Simpson SH, Lee J, Choi S. et al. Mortality risk among sulfonylureas: ansystematic review and network meta-analysis. Lancet Diabetes Endocrinol 2015; 3 (01) 43-5134
  • 53 Hemmingsen B, Schroll JB, Lund SS. et al. Sulphonylurea monotherapy for patients with type 2 diabetes mellitus. Cochrane Database Syst Rev 2013; 4: CD009008
  • 54 Hemmingsen B, Schroll JB, Jorn 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 (03) E162-E175
  • 55 Chen K, Kang D, Yu M. et al. Direct head-to-head comparison of glycaemic durability of dipeptidyl peptidase-4 inhibitors and sulphonylureas in patients with type 2 diabetes mellitus: A meta-analysis of long-term randomized controlled trials. Diabetes Obes Metab 2018; 20: 1029-1033
  • 56 Scirica BM, Bhatt DL, Braunwald E. et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369 (14) 1317-1326
  • 57 White WB, Cannon CP, Heller SR. EXAMINE Investigators. et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369 (14) 1327-1335
  • 58 Green JB, Bethel MA, Armstrong PW. et al. TECOS Study Group. N Engl J Med 2015; 373 (03) 232-242
  • 59 Rosenstock J, Perkovic V, Johansen OE. CARMELINA Investigators. et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA 2019; 321 (01) 69-79
  • 60 Monami M, Ahrén B, Dicembrini I. et al. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013; 15: 112-120
  • 61 Xu S, Zhang X, Tang L. et al. Cardiovascular effects of dipeptidylpeptidase-4 inhibitor in diabetic patients with and without established cardiovascular disease: a meta-analysis and systematic review. Postgrad Med 2017; 129: 205-215
  • 62 Zheng SL, Roddick AJ, Aghar-Jaffar R. et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes. A systematic review and meta-analysis. JAMA 2018; 319 (15) 1580-1591
  • 63 Ling J, Cheng P, Ge L. et al. The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a Bayesian network meta-analysis of 58 randomized controlled trials. Acta Diabetologica 2019; 56: 249-272
  • 64 Li L, Li S, Deng K. et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomized and observational studies. BMJ 2016; 352: i610
  • 65 Guo WQ, Li L, Su Q. et al. Effect of dipeptidylpeptidase-4 inhibitors on heart failure: A Network Meta-Analysis. Value Health 2017; 20: 1427-1430
  • 66 Nauck MA, Meier JJ, Cavender MA. et al. Cardiovascular Actions and Clinical Outcomes With Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors. Circulation 2017; 136 (09) 849-870
  • 67 Tkáč I, Raz I. Combined analysis of three large interventional trials with gliptins indicates increased incidence of acute pancreatitis in patients with type 2 diabetes. Diabetes Care 2017; 40: 284-286
  • 68 Abrahami D, Douros A, Yin H. et al. Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel disease among patients with type 2 diabetes: population based cohort study. BMJ 2018; 360: k872
  • 69 Li G, Crowley MJ, Tang H. et al. Dipeptidyl Peptidase 4 Inhibitors and Risk of Inflammatory Bowel Disease Among Patients With Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials. Diabetes Care 2019; 42 (07) e119-e121
  • 70 Storgaard H, Gluud LL, Bennett C. et al. Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. PLoS One 2016; 11 (11) e0166125
  • 71 Monami M, Liistro F, Scatena A. et al. Short and medium-term efficacy of sodium glucose co-transporter-2 (SGLT-2) inhibitors: A meta-analysis of randomized clinical trials. Diabetes Obes Metab 2018; 20 (05) 1213-1222
  • 72 Usman MS, Siddiqi TJ, Memon MM. et al. Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: A systematic review and meta-analysis. Eur J Prev Cardiol 2018; 25 (05) 495-502
  • 73 Mishriky BM, Tanenberg RJ, Sewell KA. et al. Comparing SGLT-2 inhibitors to DPP-4 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab 2018; 44 (02) 112-120
  • 74 Seidu S, Kunutsor SK, Cos X. on behalf of Primary Care Diabetes Europe. et al. SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis. Prim Care Diabetes 2018; 12 (03) 265-283
  • 75 Rådholm K, Wu JH, Wong MG. et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes – A systematic review. Diabetes Res Clin Pract 2018; 140: 118-128
  • 76 Sinha B, Ghosal S. Meta-analyses of the effects of DPP-4 inhibitors, SGLT2 inhibitors and GLP1 receptor analogues on cardiovascular death, myocardial infarction, stroke and hospitalization for heart failure. Diabetes Res Clin Pract 2019; 150: 8-16
  • 77 Zheng SL, Roddick AJ, Aghar-Jaffar R. et al. Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA 2018; 319 (15) 1580-1591
  • 78 Puckrin R, Saltiel MP, Reynier P. et al. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol 2018; 55 (05) 503-514
  • 79 Lega IC, Bronskill SE, Campitelli MA. et al. Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: A population-based study of older women and men with diabetes. Diabetes Obes Metab 2019; DOI: 10.1111/dom.13820. . [Epub ahead of print]
  • 80 Aronson R, Frias J, Goldman A. et al. Long-term efficacy and safety of ertugliflozin monotherapy in patients with inadequately controlled T2DM despite diet and exercise: VERTIS MONO extension study. Diabetes Obes Metab 2018; 20: 1453-1460
  • 81 Pratley RE, Eldor R, Raji A. et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: The VERTIS FACTORIAL randomized trial. Diabetes Obes Metab 2018; 20: 1111-1120
  • 82 Fralick M, Schneeweiss S, Patorno E. Risk of diabetic ketoacidosis after initiation of an SGLT2 inhibitor. N Engl J Med 2017; 376: 2300-2303
  • 83 Monami M, Nreu B, Zannoni S. et al. Effects of SGLT2 inhibitors on diabetic ketoacidosis: A meta-analysis of randomised controlled trials. Diabetes Res Clin Pract 2017; 130: 53-60
  • 84 Fadini GP, Bonora BM, Avogaro A. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System. Diabetologia 2017; 60: 1385-1389
  • 85 Donnan K, Segar L. SGLT2 inhibitors and metformin: Dual antihyperglycemic therapy and the risk of metabolic acidosis in type 2 diabetes. Eur J Pharmacol 2019; 846: 23-29
  • 86 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
  • 87 Wanner C, Inzucchi SE, Zinman B. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med 2016; 375: 323-334
  • 88 Cherney DZI, Zinman B, Inzucchi SE. et al. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2017; 5: 610-621
  • 89 Sattar N, McLaren J, Kristensen SL. et al. SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?. Diabetologia 2016; 59: 1333-1339
  • 90 Ferrannini E, Mark M, Mayoux E. et al. CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis. Diabetes Care 2016; 39: 1108-1114
  • 91 https://www.gba.de/downloads/40-268-4342/2017-04-20_DMP-ARL_Aenderung-Anlage-1_DMP-Diabetes-mellitus_TrG.pdf
  • 92 Neal B, Perkovic V, Mahaffey KW. et al. CANVAS Program Collaborative Group Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377: 644-657
  • 93 Perkovic V, Jardine MJ, Neal N. et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med 2019; 380: 2295-2306
  • 94 Wiviott SD, Raz I, Bonaca MP. DECLARE–TIMI 58 Investigators. et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380 (04) 347-357
  • 95 Mosenzon O, Wiviott SD, Cahn A. et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol 2019; 7 (08) 606-617
  • 96 Furtado RHM, Bonaca MP, Raz I. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction. Circulation 2019; 139 (22) 2516-2527
  • 97 Kato ET, Silverman MG, Mosenzon O. et al. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation 2019; 139 (22) 2528-2536
  • 98 www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/SGLT2_inhibitors_(previously_Canagliflozin)/human_referral_prac_000059.jsp&mid=WC0b01ac05805c5
  • 99 Scheen AJ. Does lower limb amputation concern all SGLT2 inhibitors?. Nat Rev Endocrinol 2018; 14 (06) 326-328
  • 100 Fioretto P, Del Prato S, Buse JB. et al. Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (CKD Stage 3A): The DERIVE Study). Diabetes Obes Metab 2018; DOI: 10.1111/dom.13413.
  • 101 Inzucchi SE, Iliev H, Pfarr E. et al. Empagliflozin and assessment of lower limb amputations in the EMPA-REG OUTCOME trial. Diabetes Care 2018; 41: e4-e5
  • 102 Zhou Z, Jardine M, Perkovic V. et al. Canagliflozin and fracture risk in individuals with type 2 diabetes: results from the CANVAS Program. Diabetologia 2019 published online Aug 11
  • 103 Kohler S, Kaspers S, Salsali A. et al. Analysis of Fractures in Patients With Type 2 Diabetes Treated With Empagliflozin in Pooled Data From Placebo- Controlled Trials and a Head-to-Head Study Versus Glimepiride. Diabetes Care 2018; 41 (08) 1809-1816
  • 104 Ruanpeng D, Ungprasert P, Sangtian J. et al. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis. Diabetes Metab Res Rev 2017; DOI: 10.1002/dmrr.2903.
  • 105 Tang HL, Li DD, Zhang JJ. et al. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes Obes Metab 2016; 18 (12) 1199-1206
  • 106 Levin PA, Nguyen H, Wittbrodt ET. et al. Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research. Diabetes Metab Syndr Obes 2017; 10: 123-139
  • 107 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
  • 108 Verma S, Bhatt DL, Bain SC. et al. Effect of liraglutide on cardiovascular events in patients with type 2 diabetes mellitus and polyvascular disease. Circulation 2018; 137 (20) 2179-2183
  • 109 Marso SP, Nauck MA, Monk Fries T. et al. Myocardial infarction subtypes in patients with type 2 diabetes mellitus and the effect of liraglutide therapy (from the LEADER Trial). Am J Cardiol 2018; 121: 1467-1470
  • 110 Mann JFE, Ørsted DD, Buse JB. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377: 839-848
  • 111 Kristensen SL, Rørth R, Jhund PS. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol 2019 published Online August 14
  • 112 Liu J, Li L, Deng K. et al. Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis. BMJ 2017; 357: j2499
  • 113 Gerstein HC, Colhoun HM, Dagenais GR. for the REWIND Investigators. et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019; 394: 121-130
  • 114 Gerstein HC, Colhoun HM, Dagenais GR. for the REWIND Investigators. et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet 2019; 394: 131-138
  • 115 Home PD, Ahrén B, Reusch JEB. et al. Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus: Longterm efficacy with or without rescue therapy. Diabetes Res Clin Pract 2017; 131: 49-60
  • 116 Ahrén B, Carr MC, Murphy K. et al. Albiglutide for the treatment of type 2 diabetes mellitus: An integrated safety analysis of the HARMONY phase 3 trials. Diabetes Res Clin Pract 2017; 126: 230-239
  • 117 Hernandez AF, Green JB, Janmohamed S. et al. Harmony Outcomes committees and investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 2018; 392: 1519-1529
  • 118 Holman RR, Bethel MA, Mentz RJ. et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017; 377 (13) 1228-1239
  • 119 Bethel MA, Patel RA, Merrill P. et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol 2018; 6: 105-113
  • 120 Marso SP, Bain SC, Consoli A. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375 (19) 1834-1844
  • 121 Leiter LA, Bain SC, Hramiak I. et al. Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial. Cardiovasc Diabetol 2019; 18: 73
  • 122 Husain M, Birkenfeld AL, Donsmark M. PIONEER 6 Investigators. et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2019; DOI: 10.1056.
  • 123 Zheng SL, Roddick AJ, Aghar-Jaffar R. et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes. A systematic review and meta-analysis. JAMA 2018; 319 (15) 1580-1591
  • 124 Dicembrini I, Nreu B, Scatena A. et al. Microvascular effects of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized controlled trials. Acta Diabetol 2017; 54: 933-941
  • 125 Vilsbøll T, Bain SC, Leiter LA. et al. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab 2018; 20: 889-897
  • 126 Monami M, Nreu B, Scatena A. et al. Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): Data from randomized controlled trials. Diabetes Obes Metab 2017; 19 (09) 1233-1241
  • 127 Nauck MA, Meier JJ, Schmidt WE. Incretin-based glucose-lowering medications and the risk of acute pancreatitis and/or pancreatic cancer: Reassuring data from cardio-vascular outcome trials. Diabetes Obes Metab 2017; 19 (09) 1327-1328
  • 128 Azoulay L, Filion KB, Platt RW. et al. Association Between Incretin-Based Drugs and the Risk of Acute Pancreatitis. JAMA Intern Med 2016; 176 (10) 1464-1473
  • 129 Wang T, Wang F, Gou Z. et al. Using real-world data to evaluate the association of incretin-based therapies with risk of acute pancreatitis: a meta-analysis of 1324515 patients from observational studies. Diabetes Obes Metabol 2015; 17: 32-41
  • 130 Russell-Jones D, Pouwer F, Khunti K. Identification of barriers to insulin therapy and approaches to overcoming them. Diabetes Obes Metab 2018; 20: 488-496
  • 131 Marso SP, McGuire DK, Zinman B. DEVOTE Study Group. et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. New Engl J Med 2017; 377 (08) 723-732
  • 132 Pieber TR, Marso SP, McGuire DK. et al. DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes andmortality. Diabetologia 2018; 61: 58-65
  • 133 Lau IT, Lee KF, So WY. et al. Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus. Diabetes Metab Syndr Obes 2017; 10: 273-284
  • 134 Ritzel R, Roussel R, Giaccari A. et al. Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes. Diabetes Obes Metab 2018; 20: 541-548
  • 135 Bonadonna RC, Renard E, Cheng A. et al. Switching to insulin glargine 300 U/mL: Is duration of prior basal insulin therapy important?. Diabetes Res Clin Pract 2018; 142: 19-25
  • 136 Linnebjerg H, Lam EC, Seger ME. et al. Comparison of the Pharmacokinetics and Pharmacodynamics of LY2963 016 Insulin Glargine and EU- and US-Approved Versions of Lantus Insulin Glargine in Healthy Subjects: Three Randomized Euglycemic Clamp Studies. Diabetes Care 2015; 38: 2226-2233
  • 137 Rosenstock J, Hollander P, Bhargava A. et al. Similar efficacy and safety of LY2963 016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (ELEMENT 2 study). Diabetes Obes Metabol 2015; 17: 734-741
  • 138 Yamada T, Kamata R, Ishinohachi K. et al. Biosimilar vs originator insulins: Systematic review and meta-analysis. Diabetes Obes Metab 2018; 20: 1787-1792
  • 139 But A, De Bruin ML, Bazelier MT. et al. Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study. Diabetologia 2017; 60: 1691-1703
  • 140 Maiorino MI, Chiodini P, Bellastella G. et al. Insulin and Glucagon-Like Peptide1 Receptor Agonist Combination Therapy in Type 2 Diabetes: A systematic review and meta-analysis of randomized controlled trials. Diabetes Care 2017; 40: 614-624
  • 141 Guja C, Frías JP, Somogyi A. et al. Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study. Diabetes Obes Metab 2018; 20: 1602-1161
  • 142 Rodbard HW, Lingvay I, Reed J. et al. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): A randomized, controlled trial. J Clin Endocrinol Metab 2018; 103 (06) 2291-2301
  • 143 Gentile S, Fusco A, Colarusso S. et al. A randomized, open-label, comparative, crossover trial on preference, efficacy, and safety profiles of lispro insulin U-100 versus concentrated lispro insulin U-200 in patients with type 2 diabetes mellitus: a possible contribution to greater treatment adherence. Expert Opin Drug Saf 2018; 17 (05) 445-450
  • 144 Heise T, Hövelmann U, Brøndsted L. et al. Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart. Diabetes Obes Metabol 2015; 17: 682-688
  • 145 Bowering K, Case C, Harvey J. et al. Faster Aspart Versus Insulin Aspart as Part of a Basal-Bolus Regimen in Inadequately Controlled Type 2 Diabetes: The onset 2 Trial. Diabetes Care 2017; 40 (07) 951-957
  • 146 The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015; 373: 2103-2116
  • 147 Düsing R. Therapieziele bei der Hypertoniebehandlung. Dtsch Med Wochenschr 2017; 142: 1420-1429
  • 148 Banegas JR, Ruilope LM, de la Sierra A. et al. Relationship between clinic and ambulatory blood-pressure measurements and mortality. N Engl J Med 2018; 378: 1509-1520
  • 149 Khunti K, Gomes MB, Pocock S. et al. Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: A systematic review. Diabetes Obes Metab 2018; 20: 427-437
  • 150 Gough SC, Bode B, Woo V. et al. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26- week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabet Endocrinol 2014; 2 (11) 885-893
  • 151 Diamant M, Nauck MA, Shaginian R. et al. Glucagon-Like Peptide 1 Receptor Agonist or Bolus Insulin With Optimized Basal Insulin in Type 2 Diabetes. Diabetes Care 2014; 37 (10) 2763-2773
  • 152 Ahmann A, Rodbard HW, Rosenstock J. et al. Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebocontrolled trial. Diabetes Obes Metab 2015; 17: 1056-1064
  • 153 Montvida O, Klein K, Kumar S. et al. Addition of or switch to insulin therapy in people treated with glucagon-like peptide-1 receptor agonists: A real-world study in 66 583 patients. Diabetes Obes Metab 2017; 19 (01) 108-117
  • 154 Billings LK, Doshi A, Gouet D. et al. Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial. Diabetes Care 2018; 41 (05) 1009-1016
  • 155 Catapano AL, Graham I, De Backer G. et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37 (39) 2999-3058
  • 156 Parhofer KG, Birkenfeld AL, Krone W. et al. Positionspapier zur Lipidtherapie bei Patienten mit Diabetes mellitus. Diabetologie 2018; 13 (02) S209-S213