Therapie des Typ-2-Diabetes

Rüdiger Landgraf; Monika Kellerer; Jens Aberle; Eva-Maria Fach; Baptist Gallwitz; Andreas Hamann; Hans-Georg Joost; Harald Klein; Dirk Müller-Wieland; Michael A. Nauck; Hans-Martin Reuter; Stephan Schreiber; Erhard Siegel

doi:10.1055/a-0598-0475

Diabetologie und Stoffwechsel, Table of Contents

Diabetologie und Stoffwechsel 2018; 13(S 02): S144-S165
DOI: 10.1055/a-0598-0475

DDG-Praxisempfehlung

Therapie des Typ-2-Diabetes

Rüdiger Landgraf

¹Deutsche Diabetes Stiftung, München

,

Monika Kellerer

²Zentrum für Innere Medizin I, Marienhospital Stuttgart

,

Jens Aberle

³Sektion Endokrinologie und Diabetologie, Universitäres Adipositas Zentrum Hamburg, Universitätsklinikum Hamburg-Eppendorf

,

Eva-Maria Fach

⁴Studienzentrum Stephanskirchen

,

Baptist Gallwitz

⁵Medizinische Klinik IV, Universitätsklinikum Tübingen

,

Andreas Hamann

⁶Medizinische Klinik IV, Hochtaunuskliniken gGmbH, Bad Homburg v. d. H.

,

Hans-Georg Joost

⁷Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Nuthetal

,

Harald Klein

⁸Medizinische Klinik I, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum

,

Dirk Müller-Wieland

⁹Medizinische Klinik I, Universitätsklinikum RWTH Aachen, Aachen

,

Michael A. Nauck

¹⁰Diabeteszentrum Bochum-Hattingen, St. Josef-Hospital, Ruhr-Universität, Bochum

,

Hans-Martin Reuter

¹¹Innere Medizin/Diabetologie, GP Ambulantes Medizinisches Zentrum, Jena

,

Stephan Schreiber

¹²Diabeteszentrum Schreiber, Quickborn

,

Erhard Siegel

¹³Abteilung für Innere Medizin – Gastroenterologie, Diabetologie/Endokrinologie und Ernährungsmedizin, St. Josefskrankenhaus Heidelberg GmbH, Heidelberg

› Author Affiliations

Abstract

Full Text

References

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 Nauck M, Petermann A, Müller-Wieland D. et al. Definition, Klassifikation und Diagnostik des Diabetes Mellitus. Diabetologie 2018; 13 (Suppl. 02) S90-S96
5 Landgraf R, Nauck M, Freckmann G. et al. Fallstricke bei der Diabetesdiagnostik: Wird zu lax mit Laborwerten umgegangen? Dtsch Med Wochenschr. 2018 , im Druck
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 Lawall H, Huppert P, Rümenapf G. et al. Periphere arterielle Verschlusskrankheit (PAVK), Diagnostik, Therapie und Nachsorge. AWMF Register Nr. 065 – 003; 2015
9 Nationale VersorgungsLeitlinie Neuropathie bei Diabetes im Erwachsenenalter. 2016 www.leitlinien.de/mdb/downloads/nvl/diabetes-mellitus/dm-neuropathie
10 Nationale VersorgungsLeitlinie Prävention und Therapie von Netzhautkomplikationen bei Diabetes. 2016 www.leitlinien.de/nvl/html/netzhautkomplikationen
11 Nationale VersorgungsLeitlinie (NVL) Typ-2-Diabetes Präventions- und Behandlungsstrategien für Fußkomplikationen. 2018 www.leitlinien.de/nvl/diabetes/fusskomplikationen
12 Roeb E, Steffen HM, Bantel H. et al. S2k Leitlinie: Nicht-alkoholische Fettlebererkrankungen. AWMF Register Nr. 021-025; 2015
13 Nationale VersorgungsLeitlinie Nierenerkrankungen bei Diabetes im Erwachsenenalter. 2018 www.leitlinien.de/nvl/diabetes/nierenerkrankungen
14 Nationale VersorgungsLeitlinie Chronische Herzinsuffizienz. 2018 https://www.leitlinien.de/nvl/html/nvl-chronische-herzinsuffizienz
15 Nationale Versorgungs-Leitlinie Chronische Koronare Herzerkrankung (KHK). 2016 https://www.leitlinien.de/mdb/downloads/nvl/khk/ , www.leitlinien.de/nvl/html/nvl-chronische-khk
16 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
17 Lean MEJ, Leslie WS, Barnes AC. et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 2018; 391: 541-551
18 Adipositas – Prävention und Therapie. AWMF Register Nr. 050 – 001
19 The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369: 145-154
20 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
21 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
22 www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RV_STP/m-r/metformin.html
23 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 ; published online June 4
24 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
25 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
26 Mallik R, Chowdhury TA. Metformin in cancer. Diabetes Res Clin Pract 2018 May 26. pii: S0168-8227(17)31410-9
27 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
28 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
29 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
30 Zhuang XD, He X, Yang DY. et al. Comparative cardiovascular outcomes in the era of novel anti-diabetic agents: a comprehensive network meta-analysis of 166371 participants from 170 randomized controlled trials. Cardiovasc Diabetol 2018; 17 (01) 79
31 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 , published online May 28
32 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
33 Simpson SH, Lee J, Choi S. et al. Mortality risk among sulfonylureas: ansystematic review and network meta-analysis. Lancet Diabetes Endocrinol 2015; 3 (01) 43-51
34 Fadini GP, Bottigliengo D, D’Angelo F. et al. Comparative Effectiveness of DPP4 Inhibitors Versus Sulfonylurea for the Treatment of Type 2 Diabetes in Routine Clinical Practice: A Retrospective Multicenter Real-World Study. Diabetes Ther. 2018 , published online June 1
35 Wang F, He Y, Zhang R. et al. Combination therapy of metformin plus dipeptidylpeptidase-4 inhibitor versus metformin plus sulfonylurea and their association with a decreased risk of cardiovascular disease in type 2 diabetes mellitus patients. Systematic review and meta-analysis. Medicine 2017; 96 (36) e7638
36 Hemmingsen B, Schroll JB, Lund SS. et al. Sulphonylurea monotherapy for patients with type 2 diabetes mellitus. Cochrane Database Syst Rev 2013; Apr 30; (4): CD009008
37 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
38 Sharma M, Beckley N, Nazareth I. et al. Effectiveness of sitagliptin compared to sulfonylureas for type 2 diabetes mellitus inadequately controlled on metformin: a systematic review and meta-analysis. BMJ Open 2017; 7: e017260
39 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
40 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
41 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
42 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
43 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
44 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
45 Filion KB, Azoulay L, Platt RW. et al. A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. N Engl J Med 2016; 374: 1145-1154
46 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
47 Nyström T, Bodegard J, Nathanson D. et al. Second line initiation of insulin compared with DPP4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia. Diabetes Res Clin Pract 2017; 123: 199-208
48 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
49 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
50 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
51 Müller-Wieland D, Kellerer M, Cypryk K. et al. Efficacy and safety of dapagliflozin or dapagliflozin plus saxagliptin versus glimepiride as add-on to metformin in patients with type 2 diabetes. Diabetes Obes Metab. 2018 ; publ. online Jun 27
52 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
53 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
54 Fadini GP, Bonora BM, Avogaro A. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System. Diabetologia 2017; 60: 1385-1389
55 Fralick M, Schneeweiss S, Patorno E. Risk of diabetic ketoacidosis after initiation of an SGLT2 inhibitor. N Engl J Med 2017; 376: 2300-2303
56 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
57 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
58 Kosiborod M, Cavender MA, Fu AZ. et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs. CVD-REAL study. Circulation 2017; 136: 249-259
59 Wanner C, Inzucchi SE, Zinman B. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med 2016; 375: 323-334
60 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
61 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
62 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
63 https://www.gba.de/downloads/40-268-4342/2017-04-20_DMP-A-RL_Aenderung-Anlage-1_DMP-Diabetes-mellitus_TrG.pdf
64 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
65 Ryan PB, Buse JB, Schuemie MJ. et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes Metab 2018; 1-13
66 Sonesson C, Johansson PA, Johnsson E. et al. Cardiovascular effects of dapagliflozin in patients with type 2 diabetes and different risk categories: a meta‑analysis. Cardiovasc Diabetol 2016; 15: 37
67 Toulis KA, Willis BH, Marshall T. et al. All-cause mortality in patients with diabetes under treatment with dapagliflozin: A Population-based, open-cohort study in the health improvement network database. J Clin Endocrinol Metab 2017; 102: 1719-1725
68 Persson F, Nystrom T, Jorgensen ME. et al. Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study. Diabetes Obes Metab 2018; 20: 344-351
69 Nystrom T, Bodegard J, Nathanson D. et al. Novel oral glucose lowering drugs are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes. Diabetes Obes Metab 2017; 19: 831-841
70 Wu JH, Foote C, Blomster J. et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2016; 4: 411-419
71 Monami M, Dicembrini I, Mannucci E. et al. Effects of SGLT2 inhibitors on mortality and cardiovascular events: a comprehensive meta-analysis of randomized controlled trials. Acta Diabetol 2017; 54: 19-36
72 www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/SGLT2_inhibitors_(previously_Canagliflozin)/human_referral_prac_000059.jsp&mid=WC0b01ac05805c5
73 Scheen AJ. Does lower limb amputation concern all SGLT2 inhibitors?. Nat Rev Endocrinol 2018; 14 (06) 326-328
74 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;
75 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
76 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 ; published online June 15
77 Levin PA, Nguyen H, Wittbrodt ET. et al. Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research. 2017; 10: 123-139
78 Zinman B, Marso SP, Christiansen E. et al. Hypoglycemia, Cardiovascular Outcomes, and Death: The LEADER Experience. Diabetes Care 2018; 41 (08) 1783-1791
79 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
80 Nauck MA, Tornøe K, Rasmussen S. et al. Cardiovascular outcomes in patients who experienced a myocardial infarction while treated with liraglutide versus placebo in the LEADER trial. Diab Vasc Dis Res. 2018 ; published online June 1
81 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
82 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
83 Mann JFE, Ørsted DD, Buse JB. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377: 839-848
84 Mahmoud AN, Saad M, Mansoor H. et al. Cardiovascular safety of incretin-based therapy for type 2 diabetes: A meta-analysis of randomized trials. Int J Cardiol 2017; 230: 324-326
85 Ferdinand KC, Botros FT, Atisso CM. et al. Cardiovascular safety for once‑weekly dulaglutide in type 2 diabetes: a pre-specified meta-analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol 2016; 15: 38-50
86 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: Long-term efficacy with or without rescue therapy. Diabetes Res Clin Pract 2017; 131: 49-60
87 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
88 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
89 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
90 Pratley RE, Aroda VR, Lingvay I. et SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol 2018; 6 (04) 275-286
91 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
92 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
93 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
94 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
95 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
96 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
97 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
98 Marso SP, McGuire DK, Zinman B. et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. New Engl J Med 2017; 377 (08) 723-732
99 Pieber TR, Marso SP, McGuire DK. et al. DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality. Diabetologia 2018; 61: 58-65
100 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
101 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
102 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
103 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
104 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
105 Yamada T, Kamata R, Ishinohachi K. et al. Biosimilar vs originator insulins: Systematic review and meta-analysis. Diabetes Obes Metab 2018; 20: 1787-1792
106 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
107 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
108 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
109 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
110 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
111 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: 1602-1614
112 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
113 The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015; 373: 2103-2116
114 Düsing R. Therapieziele bei der Hypertoniebehandlung. Dtsch Med Wochenschr 2017; 142: 1420-1429
115 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
116 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
117 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
118 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
119 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, placebo-controlled trial. Diabetes Obes Metab 2015; 17: 1056-1064
120 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
121 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
122 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
123 www.dgk.org
124 www.hochdruckliga.de
125 Landgraf R, Klauss V, Middeke M. et al. Perioperatives Management von Menschen mit Diabetes bei elektiven Eingriffen. Review. Teil 1. Diabetologe 2017;13:203–218; Teil 2. Diabetologe 2017;13:277–290