Type 2 Diabetes: Prototypical Chronic Illness

1. Type 2 Diabetes: Prototypical Chronic Illness Challenging Patient: Older Patient with Multiple Co-Morbidities

2. Managing Chronic Illness • Assess Adherence • Assess Risk • Monitor Disease Control • Monitor Treatment Side Effects • Monitor End-Organ Damage • Prevent End-Organ Damaage • Set Goals • Treat to Target • Educate Patient

3. The UKPDS • Most significant study of the treatment of type 2 diabetes published in 25 years • Now Six other outcomes trials evaluating “real-world” patients • University Group Diabetes Project (1975) • Increased CV mortality in patients treated with tolbutamide • “Black Box Warning” (widely ignored) • Multifactorial intervention trial of 160 patients (Steno-2) • Glucose, BP, lipid control, + ASA, ACE I, metformin (All of these were in favor of the intervention group) • Decreased composite of CV death, MI, stroke, PVD Gaede P, et al. Effect of a multifactorial intervention on mortality in type 2 DM. NEJM 2008;358:580-91. • ACCORD • ADVANCE • VADT • Pro-Active

4. Brief Review of the United Kingdom Prospective Diabetes Study (UKPDS) • 10.7-year study of 4,000 pts newly-diagnosed with type 2 diabetes • Goal 1: Evaluate value of tight (<110 mg/dL) vs. loose (<270 mg/dL) control of blood glucose • Goal 2: Evaluate value of tight (<150/85) vs. loose (<180/105) blood pressure control in diabetics

5. Findings of the UKPDS • Tight glucose control • Decreased diabetes-related outcomes (NNT = 196) • Almost all of this benefit was on the decreased need for photocoagulation • No effect on any single outcome, including visual loss • Had no effect on mortality • A1c changes did not correlate to outcomes (Stratton) • In overweight patients, metformin • Decreased mortality (NNT = 141) • Decreased diabetes-related outcomes (NNT = 74) • Independent of A1c

6. Findings of the UKPDS • Tight blood pressure • Decreased diabetes-related mortality (NNT = 152) • Decreased diabetes-related outcomes (NNT = 61) • No difference between b-blocker and ACE I • In overweight patients, sulfonylurea drugs and insulin • Hadnoeffect on diabetes-related outcomes • Hadnoeffect on mortality

7. No advantage to tight control in Type 2 DM • ACCORD. NEJM 2008;358:2545-59 • Stopped early due to increased mortality in intensive control (HBA1C<7) group • ADVANCE. NEJM 2008;358:2560-72 • Reduced microvascular but not major macrovascular events • Strong benefit to treating hypertension

8. VADT – no benefit to tight control • 1800 military veterans with poor control, mean years since diagnosis 11.5 years, 40% already with CV event. • Mean f/up 5.6 years • Intensive HbA1C- 6.9%; standard,- 8.4% • No difference in micro/macro/death • Severe hypoglycemia 24.1% v 17.6% (NNTH=15) • Duckworth et al. NEJM 2009;360:129-39

9. Tight Control Lowers CV Events

10. Tight control does not improve all cause mortality

11. Real World: Better control associated with higher mortality

12. Lending a Hand to Patients with Type 2 Diabetes Metformin/?ASA Blood pressure Cholesterol Glucose control? Smoking Slawson DC, Shaughnessy AF. Lending a Hand to Patients with Diabetes. Data from: Vijan S. Treatment of hypertension in type 2 diabetes mellitus: blood pressure goals, choice of agents, and setting priorities in diabetes care. Ann Intern Med 2003; 138:593-602.

13. 3 Control blood pressure (140/80 mmHg) 4 Add statin and aspirin (and metformin) 2 Stop smoking 5 consider tight glucose control 1 Control symptoms (diet, metformin) Don’t turn the hand around Let’s give our diabetic patients a hand!

14. What medicine to prescribe for HTN? • 31,512 patients in ALLHAT (not randomised to doxazosin arm) for whom a baseline FPG was recorded • No differences in primary outcome (fatal or non-fatal CHD) between lisinopril and chlorthalidone groups • Patients with IFG randomised to amlodipine had a higher risk of the primary outcome than those taking chlorthalidone(RR 1.73, 1.10 to 2.72, P=0.01) • Patients with DM randomised to amlodipine had a higher risk of heart failure than those taking chlorthalidone (RR 1.39, 1.22 to 1.59 P<0.001) • Patients randomised to chlorthalidone were not disadvantaged for any other outcomes compared to those in other treatment arms

15. Role of statins in type-2 diabetes • Third/fourth finger of the hand • After symptom control (smoking cessation if relevant) and control of blood pressure • Benefits appear to be around a 2030% relative risk reduction regardless of age, gender, lipid levels. • Baseline risk is the key to the size of the absolute benefits • Should all those with type 2 diabetes be on a statin? • Which statin: • Evidence is for simvastatin 40mg/day or atorvastatin 10mg/day

16. Role of Home Blood Sugar Monitoring • Cochrane, 2004 – Systematic review of poor quality trials – perhaps some sl. benefit • Diabetes Care, 2005 – Meta-analysis of 6 poor quality trials – min hgba1c benefit • BMJ 2007 – RCT – no difference, increase in hypoglycemia • BMJ 2008 – RCT – no difference, increased depression

17. What about ASA • IF CAD • Or DM plus one additional risk factor • Younger, without co-morbidities, do not need ASA

18. Summary for prescribers • Think CV risk, not blood glucose – Set Goals • Treating blood pressure is more important than worrying about drug choice • Low dose thiazidesare safe and well tolerated (ALLHAT) • ACE inhibitors also a reasonable first choice • Many will need combinations to achieve target BP • Still concern about CCBs in patients with diabetes • Why use ARBs or doxazosin, unless you really need to? • Is the emphasis on tight blood glucose control justified by the evidence? • Metformin in everyone with Type-2 DM? • Do patients really need to self monitor their blood glucose as often as they do? • Manage overall risk ( • Polypharmacyis the norm! (and needs support)