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![Numbers Needed to Treat
[To prevent 1 CVD event]
Glucose (HbA1c 0.9%) : 119
Cholesterol trials (1mM) 44
Blood Pressure trials (10/6mmHg) 34
Yudkin et al, Diabetologia 2010](https://image.slidesharecdn.com/edwingale-costeffectivediabetestreatment-120324160603-phpapp01/75/Edwin-gale-cost-effective-diabetes-treatment-27-2048.jpg)
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Edwin gale.cost effective diabetes treatment
This document discusses effective and cost-effective treatment for diabetes. It summarizes the key points made in the document in 3 sentences: Intensified glucose control alone offers limited benefits for type 2 diabetes patients, as it provides only weak protection against cardiovascular outcomes and has not been shown to improve life expectancy. Combined treatment of all cardiovascular risk factors can significantly improve outcomes. The best approach is to consider a patient's individual prognosis, risks, and preferences when determining the appropriate treatment goals and therapies.
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Edwin gale.cost effective diabetes treatment
- 1. Effective and Cost-Effective Treatment for Diabetes Edwin Gale Edwin Gale University of Bristol, UK
- 2. I have nofinancial conflicts of interest
- 3. Effective and Cost-EffectiveTreatment The scope of the problem What are we trying to achieve? Choosing the right treatment
- 4. Most of themedical textbooks are based upon experience gained in Western populations. The culture, phenotype and genotype of diabetes differs between major population groups Egyptian people should rewrite the textbooks for use in Egypt!
- 5. A Century ofEconomic Growth High employment, increasing disposable income, cheap food and energy (and everything that goes with these things) are changing the phenotype of the human species The changing phenotype of the human species (affluent variety) Diabetologia 2004;47:1339-1342
- 6. Health Correlates ofEconomic Growth: A Changing Human Phenotype Increasing height: 1 cm/decade Changing body proportions Increasing weight-to-height ratio Increasing longevity: 3-4 months for every calendar year
- 7. Estimated Numbers withDiabetes (in millions) in 2000 and 2030 Western Countries Growing economies
- 9. Diabetes Prevalence as% Population in Denmark Courtesy of Bendix Carstensen
- 10. Diabetes Prevalence as% Population in Denmark Courtesy of Bendix Carstensen
- 11. The Affluent Phenotype BP Lipids Atheroma Glucose Cancer
- 12. Excess calorie intakeis a major driver of the affluent phenotype … … and reduced calorie intake reverses most Edwin Gale of its features
- 13. Incidence of diabetesin Oslo, 1925-54 Westlund 1966
- 14. Diabetes Mortality inthe UK, 1938-58 World War II Deaths/ 100k Trowell, 1962
- 15. Calorie restriction isthe only form of therapy that strikes at the root cause of diabetes Pharmacotherapy largely represents the attempt to compensate for a failure of Edwin Gale calorie restriction
- 16. Summary: The HumanPhenotype Affluent humans are developing a new and distinctive phenotype Diseases of relative overnutrition have emerged as the leading causes of death Increasing longevity is a major factor in the diabetes epidemic
- 17. Effective and Cost-EffectiveTreatment The scope of the problem What are we trying to achieve? Choosing the right treatment
- 18. What are wetrying to achieve? 1. Near-normal glucose control? 2. Near-normal life expectancy? 3. Near-normal life quality?
- 19. Near-normal glucose control Offers strong protection against microvascular complications - but the benefit diminishes with increasing age But weak protection against cardiovascular outcomes Has not been shown to improve life expectancy in type 2 diabetes Intensified glucose control can reduce
- 20. Lifetime Risk ofBlindness by Age at Diagnosis and HbA1c n/1000 Age at diagnosis Ann Int Med 1997;127:788
- 21. Lifetime Risk ofESRF by Age at Diagnosis and HbA1c n/1000 Age at diagnosis Ann Int Med 1997;127:788
- 22. Microvascular Disease Risk diminisheswith age and/or limited life expectancy. The full benefits seen in young patients with type 1 diabetes are not achieved in older people with type 2 diabetes
- 23. Near-normal glucose control Offers strong protection against microvascular complications But weak protection against cardiovascular outcomes Has not been shown to improve life expectancy in type 2 diabetes Intensified glucose control can reduce quality of life
- 24. HRs for CVoutcomes, DM vs non-diabetes Emerging Risk Factors Collaboration (EFRC), Lancet 2010;375:2215-22
- 25. Emerging Risk FactorsCollaboration (EFRC), NEJM 2011;364:829-41
- 26. A 50-year-old manwith diabetes loses 6 years of life expectancy 60% of the excess mortality is due to vascular deaths Emerging Risk Factors Collaboration (EFRC), NEJM 2011;364:829-41
- 27. Numbers Needed toTreat [To prevent 1 CVD event] Glucose (HbA1c 0.9%) : 119 Cholesterol trials (1mM) 44 Blood Pressure trials (10/6mmHg) 34 Yudkin et al, Diabetologia 2010
- 28. Near-normal glucose control Offers strong protection against microvascular complications But weak protection against cardiovascular outcomes Has not been shown to improve life expectancy in type 2 diabetes Intensified glucose control can reduce quality of life
- 29. Mortality – intensiveversus standard Meta-Analysis: 13 studies, 34533 patients All cause mortality OR: 1.04 (0.91 – 1.19) Cardiovascular death OR: 1.11 (0.96 – 1.43) Boussageon R et al. BMJ 2011
- 30. Relationship Between GlycatedHaemoglobin and Mortality in 47,970 Patients Oral therapy Insulin UK General Practice Research Database, Currie et al, Lancet 2010
- 31. Near-normal glucose control Offers strong protection against microvascular complications But weak protection against cardiovascular outcomes Has not been shown to improve life expectancy in type 2 diabetes Intensified glucose control can reduce quality of life
- 32. Patient perceptions ofintensive glucose lowering 701 pts with T2DM asked re QOL utilities; a score of 1.0 = perfect health, 0 = death Intensive glucose control scored 0.67, or 1/3 of a year‟s quality of life Huang et al, Diabetes Care (2007) 30:2478
- 33. Check Point Intensified glucose lowering therapy ALONE offers limited benefits in type 2 diabetes BUT Combined attention to all cardiovascular risk factors can make a dramatic difference to outcomes
- 34. STENO-2 Randomized 160 NEJM 2008;358:580 80 80 Trial Ends 67 63 Mean 7.8 yr 55 38 Study Ends Mean 5.5 yr Died 24 (9 CVD) 40 (19 CVD) Intensified Conventional (1 dropped out) (2 dropped out)
- 35. Effective and Cost-EffectiveTreatment The scope of the problem What are we trying to achieve? Choosing the right treatment
- 36. When? Why? Who? How?
- 37. When? Why? LifeQuality CV Risk Other risks Longevity
- 38. When? Does intensified Why? therapy benefit? Life Quality CV Risk Other risks Longevity Hemmingsen B et al: Cochrane Database Syst Rev. 2011 Jun 15;6:CD008143 Yudkin et al, Diabetologia 2010;53:2079-85
- 39. When? Does intensified Why? therapy benefit? Life Quality No CV Risk Other risks Longevity Hemmingsen B et al: Cochrane Database Syst Rev. 2011 Jun 15;6:CD008143 Yudkin et al, Diabetologia 2010;53:2079-85
- 40. When? Does intensified Why? therapy benefit? Life Quality No CV Risk Marginal Other risks Longevity Hemmingsen B et al: Cochrane Database Syst Rev. 2011 Jun 15;6:CD008143 Yudkin et al, Diabetologia 2010;53:2079-85
- 41. When? Does intensified Why? therapy benefit? Life Quality No CV Risk Marginal Other risks Minor Longevity Hemmingsen B et al: Cochrane Database Syst Rev. 2011 Jun 15;6:CD008143 Yudkin et al, Diabetologia 2010;53:2079-85
- 42. When? Does intensified Why? therapy benefit? Life Quality No CV Risk Marginal Other risks Minor Longevity No Hemmingsen B et al: Cochrane Database Syst Rev. 2011 Jun 15;6:CD008143 Yudkin et al, Diabetologia 2010;53:2079-85
- 43. When? Does intensified Why? therapy benefit? Life Quality No CV Risk Marginal But early intervention Other risks Minor is beneficial! Longevity No Hemmingsen B et al: Cochrane Database Syst Rev. 2011 Jun 15;6:CD008143 Yudkin et al, Diabetologia 2010;53:2079-85
- 44. VADT - HRfor Primary Outcome in Intensive Arm 1.4 1.2 Hazard Ratio 1 0.8 0.6 0.4 0.2 0 0 3 6 9 12 15 18 21 24 Duration of Diabetes (yrs)
- 45. When? Why? How?
- 46. Comorbidity and GlucoseControl, New onset patients aged 60-64 yrs Comorb. Life Exp Days added Case 1 0 14.6 yrs +106 Case 2 3 9.7 yrs + 44 Case 3 7 4.8 yrs + 8 Huang et al, Ann Int Med (2008) 149:11-19
- 47. When? Why? Who? Life Quality Life Quality CV Risk CV Risk Other risks Other risks Longevity Longevity
- 48. When? Why? Who? Life Quality Life Quality Prognosis, patient choice CV Risk CV Risk Other risks Other risks Longevity Longevity
- 49. When? Why? Who? Life Quality Life Quality Prognosis, patient choice CV Risk CV Risk Other risks Other risks Established vascular disease? Longevity Longevity
- 50. When? Why? Who? How?
- 51. When? Why? Who? How? Life Quality Life Quality Life Quality CV Risk CV Risk CV Risk Other risks Other risks Other risks Longevity Longevity Longevity
- 52. When? Why? Who? How? Life Quality Diabetes therapies previously considered solely in terms of CV Risk HbA1c reduction ... Other risks Longevity
- 53. Spot Quiz • TreatmentA lowers HbA1c from 10.5% to 9% • Treatment B lowers HbA1c from 7.6% to 7% • Which treatment is more potent?
- 54. HbA1c: Baseline vs.change Diabetes Care 2006;29:2137
- 55. When? Why? Who? How? Diabetes therapies previously Life Quality considered solely in terms of CV Risk HbA1c reduction ... Other risks But global profile now seen as more important Longevity
- 56. Check Point Most patientshave been exposed to multiple treatments RCT evidence does not (with some exceptions) allow us to assess the global impact of specific therapies upon cardiovascular risk
- 57. Glucose-lowering Agents Core therapies: Biguanides Sulfonylureas Human Insulin Newer therapies: Thiazolidinediones DPP-4 inhibitors GLP-1 agonists Other: Acarbose Meglitinides SGLT-2 inhibitors
- 58. ADA / EASDGuidelines Revised Treatment Algorithm At diagnosis: STEP 1 Lifestyle + metformin Tier 1* Tier 2† HbA1C >7.0% STEP 2 Add basal Add Add GLP-1 Add pioglitazone insulin sulfonylurea agonist ± SU STEP 3 Intensive insulin Nathan et al. Diabetes Care 2008
- 59. Core Therapies Lifestyle Metformin Human insulin SUs
- 60. Lifestyle … Is thestarting point for any treatment No treatment for diabetes can work effectively without adjustment of lifestyle Diabetes conferences are 90% about pharmacology and 10% about human behaviour Real world therapy is the other way round
- 61. Reduces CV disease! ? METFOR MIN Fights cancer!
- 62. Myocardial Infarction HazardRatio (fatal or non-fatal myocardial infarction or sudden death) Intensive (metformin) vs. Conventional glucose control HR (95%CI) UKPDS 80
- 63. Metformin in Patientswith Established Atherosclerosis Method: Comparison of 2 year mortality in 19,691 patients with diabetes and known vascular disease, treated with or without metformin, in the REACH registry. Roussel et al, Arch Int Med 2010;170:1892-99
- 64. Metformin in Patientswith Established Atherosclerosis +Metformin -Metformin % Mortality 6.3 (5.2-7.4) 9.8 (8.4-11.2%) Hazard Ratio 0.76 (0.65-0.89) (adjusted) Roussel et al, Arch Int Med 2010;170:1892-99
- 65. Benefits of Metformin (Hazard Ratios) Age 65-80 0.77 (0.62-0.95) Heart failure 0.69 (0.54-0.90) GFR 30-60 0.64 (0.48-0.86) MF + INS 0.64 (0.46-0.89) Roussel et al, Arch Int Med 2010;170:1892-99
- 66. Metformin: Summary Mechanism ofcardiovascular protection unclear – related to mechanism of cancer protection? Observational studies to date show consistent reductions in overall and cardiovascular mortality
- 67. Sulfonylureas Gloyn et al,New Engl J Med 2004;350:1838-1849
- 68. Closure of theK+ channel leads to membrane depolarization
- 69. KATP channels Transducers betweenintracellular energy metabolism and electrical excitability Found in many tissues including heart and brain Mostly closed in tissues outside the beta cell; open in response to ischaemia, hormones or neurotransmitters In cardiac muscle and neurones the reduction in electrical activity protects against damage Frances Ashcroft, J Clin Invest 2005;115;2047-58
- 70. Variant forms ofthe channel Kir 6.2 SUR1 beta cells Kir 6.2 SUR2A cardiomyocytes Kir 6.2 SUR2B arterial smooth muscle All sulfonylureas show some cross-reactivity
- 71. Potential cardiovascular consequences of failure to open KATP channels The default setting for cardiovascular KATP channels is closure. Opening results in - • Limitation of myocardial damage during ischaemia • Loss of preconditioning • Masking of ST segment elevation • Loss of smooth muscle relaxation in coronary arteries Bell, CMAJ 2006;174:185-6
- 72. Myocardial Infarction HazardRatio (fatal or non-fatal myocardial infarction or sudden death) Intensive (SU/Ins) vs. Conventional glucose control HR (95%CI) UKPDS 80
- 73. Sulfonylureas: Summary No clear evidence that theoretical risk translates into actual risk No clear evidence that prognosis worse after myocardial infarction Best avoided in interventional cardiology Gliclazide probably safer than glibenclamide
- 74. Disadvantages of NewerTherapies Benefits overstated Unsupported claims “Newer” may not mean „better” Evidence base not yet established Long term safety unknown Much more expensive!
- 76. A Situation ofDiminishing Returns Analogs DPP4s SUs TZDs Metformin Insulin 1920 1960 2010
- 77. And Escalating Costs 1500 Rosiglitazone Pioglitazone Sitagliptin 1000 Euros/yr Analog + Lantus Metformin 500 Gliclazide Human Pork UK Formulary, 2006
- 78. Costs as %total Costs of glucose- lowering medication in England Currie et al, Diabet Med 2010;27:744-52
- 79. Costs as %total Total Costs (£m) Adjusted to 2008 Currie et al, Diabet Med 2010;27:744-52
- 80. Costs as %total Total Costs (£m) Adjusted to 2008 Costs (in England) 2000 = £289.9 million 2008 = £590.4 million Currie et al, Diabet Med 2010;27:744-52
- 81. Prescriptions by Costand Volume (2008) Currie et al, Diabet Med 2010;27:744-52
- 82. Insulin costs (£)per 1000 units BNF (accessed Oct 2011)
- 83. Insulin costs (£)per 1000 units Cumulative excess cost of analogues to the NHS is ~£650 million Currie et al, BMJ in press
- 85. Overall Summary Metformin emerges as “best buy” The disadvantages of the sulfonylureas have been over-stated Analogue insulins have marginal benefits only in type 2 diabetes Newer therapies should be reserved for second line use
- 86. Where Next? Future clinicaltrials will need to evaluate global risks and benefits of individual therapies (and combinations) rather than focusing on glucose-lowering efficacy
- 87. The Physician’s Prayer Frominability to let well alone, From too much zeal for the new and contempt for what is old, From putting knowledge before wisdom, Science before art and cleverness before common sense, From treating patients as cases And from making the cure of the disease more grievous than the endurance of the same, Good Lord deliver us. Sir Robert Hutchison (1871-1960)
- 88.