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1、Aims,What is the ideal HbA1c?Legacy effectBlood Pressure:can we go too low?Cholesterol targets,and the role of FibratesWho should have aspirin?Case ScenariosWhat drugs to use after metformin?When to use insulin and which one?Anything else?,What is the ideal HbA1c,UKPDS dataDCCT and EDIC trialADVANCE
2、ACCORDSTENOVADT,HbA1c,cross-sectional,median values,UKPDS 80 Legacy of Long-term Glycaemic Control(30 Year Follow Up Data),Legacy Effect of Earlier Glucose Control,ACCORD ADVANCE and VADT-No Significant Effect on MacroVascular Outcomes,Summary of ACCORD,ADVANCE and VADT:Outcomes,intensive vs.standar
3、d,*p0.05,ACCORD Retinal Conclusion,Intensive glycemic control and intensive combination treatment of dyslipidemia,but not intensive blood-pressure control,reduced the rate of progression of diabetic retinopathy.(Funded by the National Heart,Lung,and Blood Institute and others;ClinicalTrials.gov numb
4、ers,NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.),ADVANCE,4.3 years of follow-up:Perindopril/indapamideBlood pressure reduced 7.1 0.3 mmHg systolic and 2.9 0.2 mmHg diastolic(P 0.001).135/75:140/77(baseline 145/81)HbA1C was reduced by 0.61 0.02%after 4.3 years(P 0.001).
5、Glicazide MR,VADT Conclusion,Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events,death,or microvascular complications,with the exception of progression of albuminuria(P=0.01),VADT in the Context of the“Nat
6、ural History”of Type 2 Diabetes,Mean Systolic Blood-Pressure Levels at Each Study Visit,The ACCORD Study Group.N Engl J Med 2010;362:1575-1585,ACCORD BP Conclusion,In patients with type 2 diabetes at high risk for cardiovascular events,targeting a systolic blood pressure of less than 120 mm Hg,as co
7、mpared with less than 140 mm Hg,did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events,ACCORD lipid Conclusion,The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events,nonfatal myocardial infarction,or nonfatal st
8、roke,as compared with simvastatin aloneThese results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes,Hazard Ratios for the Primary Outcome in Prespecified Subgroups,The ACC
9、ORD Study Group.N Engl J Med 2010;362:1563-1574,Diabetes and Aspirin Guidance,Yes in secondary preventionPrimary prevention should be on an individual basis with consideration of the benefits and harms of aspirin,taking into account the presence of risk factors for vascular disease(including conditi
10、ons such as diabetes)and the risk of gastrointestinal bleeding.MHRA Drug Safety Update.October 2009.,Diabetes and Aspirin Guidance,Primary prevention:over 50,smoker,treated for hypertension and high cholesterol:yesUnder 50 with all factors and FH:yes from age 40Under 50:noOver 50 non-smoker only DM:
11、noOver 50 treated for hypertension,and high cholesterol:probably yes,Aspirin and Diabetes,The ASCEND Study is a large multi site study recruiting 10,000 patients over 40 with type 2 diabetes designed to answer the question whether aspirin should be prescribed routinely in diabetic patients.(2011)ACC
12、EPT-D Italian study 5000 patients,greater than 50.(aspirin/placebo)2007 started,NICE Guidelines:General Recommendations,Structured diabetes education,and aim for good glucose control early on in the diagnosis(metformin early).Target HbA1c of 6.5%for Type 2 Diabetes in general,but avoid pursuing high
13、ly intensive management of levels less than 7%in those with limited life expectancy 5 years),especially if using drugs which can generate hypoglycaemia Blood pressure target of less than 140/80 mmHg(No legacy effect)Simvastatin 40 mg or equivalent for all patients with Type 2 diabetes aged over 40,i
14、rrespective of experience of CV disease.,Monotherapy with 1st or 2nd Generation SUs was Associated with 24-61%Excess Risk For All Cause Mortality Compared with Metformin Monotherapy(P0.001),2.0,1.5,1.0,0.5,1st Generation sulphonylureas v metformin,2nd Generation sulphonylureas v metformin,All rosigl
15、itazone*v metformin,All pioglitazone*v metformin,All rosiglitazone*v all pioglitazone*,Other combinations v metformin,Tzoulaki et al.,BMJ 2009;339:b4731,Hazard Ratio(95%CI)(Log Scale),*Any therapy(monotherapy and combinations).Other drugs and combinations of any oral antidiabetes drugs excluding ros
16、iglitazone and pioglitazone,Model 2 results,ACCORD:Mortality HR for Individual Agents,1 ACCORD Study Group.Effects of Intensive Glucose Lowering in Type 2 Diabetes.N Engl J Med 2008;358:2545-59 2.ACCORD Webcast presented at the American Diabetes Association,6-10 June 2008.Available at:http:/www.diab
17、etesconnect.org/StoreTemplate/default.aspx?ReturnUrl=%2fDefault.aspx 5.Cefalu,WT.N Engl J Med 2008;358(24):2633-2635.6.Avandia SPC March 2008,A 40 year old Supermarket Worker,A 40 year old lady has a 2 year history of type 2 diabetes.Her glycaemic control is consistently poor.She is an ex-smoker wit
18、h a BMI of 49.Her current medication includes Aspirin 75 mg OD,Lisinopril 20 mg OD,Simvastatin 20 mg OD,Metformin 850 mg BD.Examination reveal BP of 175/70 mm/hg,peripheral pulses are normal with no evidence of neuropathy.Fundoscopy reveals early background retinopathy.Hba1c-8.5%TC-5.7 mmol/l LDL-C-
19、3.5 mmol/l HDL-C-0.9 mmol/l Plasma TG-2.6 mmol/l U/E-Normal LFT-NormalMicroalbuminuria screen-positive How would you further manage this patient?,PATIENT MRS X,78 type 2 DM BMI 28 HbA1C 8.5%,no complicationsMetformin intolerant?Metformin MRBP 145/89,Normal ACR,Chol 6.5,Hdl 1.3SUs,PioGlitazone,or(Sit
20、a)gliptinTarget HbA1c?,OPTions,BMI 35 gliptin?Exenatide,avoid sulphonylureas earlyElderly avoid sulphonylureas early,aim for reasonable control HbA1c 7.5%BMI 30 Sus after MetforminBMI 30-35 age,renal function,weight changes,?SU,gliptin or Pioglitazone second.Known IHD consider Pioglitazone after met
21、formin unless heart failure,Insulin Costs,Mixtures:Human versus analoguesNo evidence of difference,?Increased risk of Hypoglycaemia.90%of type 2 patients do as well on cheaper human mixtureSAVINGS:100 patients around 15/month/patient=20000 per year,Insulins and Costs,Night time insulin:NPH-no eviden
22、ce of difference in control,weight gain,?Increased hypoglycaemia20 per month difference:100 patients 24,000 per annum,Ambery P et al.Poster presented at Diabetes UK annual professional conference,2005.P120.,Approximately 60%of Monotherapy Patients are Missing Glycaemic Targets,HbA1c 7%,HbA1c 710%,HbA1c 10%,40%,7%,53%,www.bathdiabetes.org,
