1. Reducing the Risk of Developing Diabetes Chapter 5 Thomas Ransom, Ronald Goldenberg, Amanda Mikalachki, Ally PH Prebtani, Zubin Punthakee Canadian Diabetes Association 2013 Clinical Practice Guidelines

2. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Key Points 1.At this time, there are no safe and effective strategies to prevent T1DM 2.Intensive lifestyle modification with weight loss can reduce the risk of progression from pre-diabetes to T2DM by almost 60% 3.Progression from pre-diabetes to T2DM can be reduced by Metformin or Acarbose by approximately 30% 2013

3. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association No Safe and Effective Strategies to Prevent T1DM at this Time T1DM is a chronic autoimmune condition with destruction of pancreatic beta cells Ongoing or completed trials – ENDIT: High-dose nicotinamide – Not effective – DPT-1: Low-dose insulin in high risk relatives – Not effective overall – TRIGR: Exclusion of cow’s milk protein to infants until 6- 8 months of age – Trial ongoing Alternate strategy to use immunosuppression / modulation at the time of diagnosis but significant side effects and ethical considerations

4. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Diabetes Prevention Program (DPP) Diabetes Prevention Program (DPP) Research Group. N Engl J Med 2002;346:393-403. Years Benefit of diet and exercise or Metformin on diabetes prevention in at-risk patients N = 3234 with IFG and IGT, without diabetes 0 0 10 20 30 40 1.02.03.04.0 Placebo Metformin Lifestyle Cumulative incidence of diabetes (%)  31%  58% P* < 0.001 *vs placebo IFG = impaired fasting glucose, IGT = impaired glucose tolerance

5. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association STOP-NIDDM Study Effects of Acarbose on the risk of T2DM Chiasson JL, et al. Lancet 2002;359:2072-77. N = 1429 people with IGT, BMI 25-40, 40-70 yrs, 3.3 years follow up Days after randomization Cumulative probability P = 0.0022 0 Acarbose Placebo 100200300400 500 600 700 800900 1000110012001300 1.00 0.95 0.90 0.50 0.45 0.40 0.65 0.60 0.55 0.80 0.75 0.70 0.85 Acarbose  25%

6. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Pharmacology to Reduce Progression to T2DM Metformin has been shown to reduce the incidence of T2DM by approximately 30% in the Diabetes Prevention Program (DPP) Acarbose has been shown to reduce the risk of progression to diabetes by approximately 30% in the Study to Prevent Non-Insulin Dependent Diabetes (STOP-NIDDM) study

7. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 1 and 2 1.A structured program of lifestyle modification that includes moderate weight loss and regular physical activity should be implemented to reduce risk of T2DM in individuals with IGT [Grade A, Level 1A] or IFG [Grade B, Level 2] or A1C 6.0-6.4% [Grade D, consensus]. 2.In individuals with IGT, pharmacologic therapy with Metformin [Grade A, Level 1A] or Acarbose [Grade A, level 1A] may be used to reduce the risk of T2DM. 2013

8. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association CDA Clinical Practice Guidelines http://guidelines.diabetes.cahttp://guidelines.diabetes.ca – for professionals 1-800-BANTING (226-8464) http://diabetes.ca http://diabetes.ca – for patients