1. Prediabetes
Management

2. AACE Prediabetes Consensus Statement: Summary
Untreated individuals with prediabetes are at increased risk for diabetes as well as for micro- and macrovascular complications
Treatment goals are to prevent deterioration in glucose levels and modify other risk factors such as obesity, hypertension, and dyslipidemia
The same blood pressure and lipid goals are suggested for prediabetes and diabetes
Intensive lifestyle management is the cornerstone of all prevention efforts; pharmacotherapy targeted at glucose may be considered in high-risk patients
Handelsman Y, et al. Endocr Pract. 2011;17(Suppl 2):1-53.
Garber AJ, et al. Endocr Pract. 2008;14:

3. Prediabetes
Epidemiologic evidence suggests that the complications of T2DM begin early in the progression from NGT to frank diabetes
Prediabetes and diabetes are conditions in which early detection is appropriate, because
Duration of hyperglycemia is a predictor of adverse outcomes
There are effective interventions to prevent disease progression and to reduce complications
NGT, normal glucose tolerance ; T2DM , type 2 diabetes mellitus.
Garber AJ, et al. Endocr Pract. 2008;14:

4. Policy Paradigm Shifts Needed to Stem Global Tide of T2DM
Integrating primary and secondary prevention along a clinical continuum
Early detection of prediabetes and undiagnosed diabetes
Implementing cost-effective prevention and control by integrating community and clinical expertise/resources within affordable service delivery systems
Sharing and adopting evidence-based policies at the global level
T2DM , type 2 diabetes mellitus.
Narayan KM, et al. Health Aff (Millwood). 2012;31:84-92.

6. Feasibility of Preventing T2DM
There is a long period of glucose intolerance that precedes the development of diabetes
Screening tests can identify persons at high risk
There are safe, potentially effective interventions that can address modifiable risk factors:
Obesity
Body fat distribution
Physical inactivity
High blood glucose
T2DM, type 2 diabetes mellitus.
Garber AJ, et al. Endocr Pract. 2008;14:

7. Interventions to Reduce Risks Associated With Prediabetes
Therapeutic lifestyle management is the cornerstone of all prevention efforts
No pharmacologic agents are currently approved for the management of prediabetes
Pharmacotherapy targeted at glucose may be considered in high-risk patients after individual risk-benefit analysis
Garber AJ, et al. Endocr Pract. 2008;14:

8. Lifestyle Intervention in Prediabetes
Persons with prediabetes should reduce weight by 5% to 10%, with long-term maintenance at this level
A diet that includes caloric restriction, increased fiber intake, and (in some cases) carbohydrate intake limitations is advised.
A program of regular moderate-intensity physical activity for minutes daily, at least 5 days a week, is recommended
Garber AJ, et al. Endocr Pract. 2008;14:

9. Primary Care-Based Counseling for T2DM Prevention: ADAPT
ADAPT, Avoiding Diabetes Thru Action Plan Targeting; T2DM , type 2 diabetes mellitus.
Mann DM, Lin JJ. Implement Sci. 2012;23:6.

10. Self-Reported Risk Reduction Activities in Patients With Prediabetes
National Health and Nutrition Examination Survey
Patients
CDC. MMWR Morb Mortal Wkly Rep. 2008;57:

11. Prevention of Diabetes: Lifestyle Studies
Prediabetes Management
Prevention of Diabetes: Lifestyle Studies

12. Prevention of T2DM: Selected Lifestyle Modification Trials
Study
Country N
Baseline BMI
(kg/m2)
Intervention period
(years)
RRR
(%)
NNT
Diabetes Prevention Program
USA
3234
34.0
2.8 58 21
Diabetes Prevention Study
Finland
523 31 4 39 22
Da Qing
China
577
25.8 6 51 30
BMI, body mass index; NNT, number needed to treat; RRR, relative risk reduction; T2DM, type 2 diabetes mellitus.
DPP Research Group. N Engl J Med. 2002;346: Eriksson J, et al. Diabetologia. 1999;42: Li G, et al. Lancet. 2008;371: Lindstrom J, et al. Lancet. 2006;368:

13. T2DM Incidence in the Diabetes Prevention Program
31%
58%
per 100 person-years
T2DM incidence
Intensive lifestyle intervention*
(n=1079)
Metformin 850mg BID
(n=1073)
Placebo
(n=1082)
*Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥150 min/week moderate intensity exercise.
IGT, impaired glucose tolerance; T2DM, type 2 diabetes mellitus.
DPP Research Group. N Engl J Med. 2002;346:

14. Effect of Age on Incidence of T2DM in the DPP
48%
per 100 person-years
T2DM incidence
59%
71%
Age (years)
*Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥150 min/week moderate intensity exercise.
DPP, Diabetes Prevention Program;.
DPP Research Group. N Engl J Med. 2002;346:

15. Effect of Weight on T2DM Incidence in the DPP
51%
per 100 person-years
T2DM incidence
65%
61%
BMI (kg/m2)
*Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥150 min/week moderate intensity exercise.
DPP, Diabetes Prevention Program.
DPP Research Group. N Engl J Med. 2002;346:

16. 10-Year Weight Loss in the DPP Outcomes Study3 2 5 4 7 6 8 10 9
Years
DPP, Diabetes Prevention Program; T2DM, type 2 diabetes mellitus.
DPP Research Group. Lancet. 2009;374:

17. 10-Year Incidence of T2DM in the DPP Outcomes Study3 2 5 4 7 6 8 10 9
Placebo
Metformin
Lifestyle
Years
DPP, Diabetes Prevention Program; T2DM, type 2 diabetes mellitus.
DPP Research Group. Lancet. 2009;374:

18. 10-Year Incidence of T2DM in the DPP Outcomes Study
DPP, Diabetes Prevention Program; DPPOS, Diabetes Prevention Program Outcomes Study; T2DM, type 2 diabetes mellitus.
DPP Research Group. Lancet. 2009;374:

19. T2DM Prevention in Women With a History of GDM: Effect of Metformin and Lifestyle Interventions
Findings from the DPP:
Progression to diabetes is more common in women with a history of GDM vs those without, despite equivalent degrees of IGT at baseline
Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM
DPP, Diabetes Prevention Program; GDM, gestational diabetes mellitus;
IGT, impaired glucose tolerance; T2DM, type 2 diabetes mellitus.
Ratner RE, et al. J Clin Endocrinol Metab. 2008;93:

20. T2DM Prevention in Women With a History of GDM: Effect of Metformin and Lifestyle Interventions
Findings from the DPP:
Progression to diabetes is more common in women with a history of GDM vs those without, despite equivalent degrees of IGT at baseline
Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM
DPP, Diabetes Prevention Program; GDM, gestational diabetes mellitus;
IGT, impaired glucose tolerance; T2DM, type 2 diabetes mellitus.
Ratner RE, et al. J Clin Endocrinol Metab. 2008;93:

21. The Finnish Diabetes Prevention Study: Lifestyle Modifications
Change from baseline
P<0.001
P<0.001
P=0.007
P=0.02
DBP, diastolic blood pressure; SBP, systolic blood pressure.
Tuomilehto J, et al. N Engl J Med. 2001;344:

22. The Finnish Diabetes Prevention Study: Lifestyle Modifications
Change from baseline
P=0.003
P=0.001
(mg/dL)
(mg/dL)
(mg/mL)
(g/mL)
DBP, diastolic blood pressure; SBP, systolic blood pressure.
Tuomilehto J, et al. N Engl J Med. 2001;344:

23. (cases/1000 person-years)
The Finnish Diabetes Prevention Study: Cumulative Incidence of Diabetes Over 4 Years
58%
(cases/1000 person-years)
Incidence of diabetes
DBP, diastolic blood pressure; SBP, systolic blood pressure.
Tuomilehto J, et al. N Engl J Med. 2001;344:

24. Da Qing: Cumulative Incidence of Diabetes at 6-Year Evaluation
Patients with IGT (N=577)
Patients with T2DM at Year 6 (%)
IGT, impaired glucose tolerance.
Pan XR, et al. Diabetes Care. 1997;20:

25. Cumulative T2DM Incidence During Follow-up in the Chinese Da Qing Diabetes Prevention Study
CI, confidence interval; DPP, Diabetes Prevention Program; T2DM, type 2 diabetes mellitus.
Li G, et al. Lancet. 2008;371:

26. Group Lifestyle Balance Program Intervention
University of Pittsburgh Primary Care Practice and Diabetes Prevention Support Center  
DPP lifestyle intervention was adapted to a 12-session group-based program
Implemented in a community setting in 2 phases using a nonrandomized prospective design
Significant decreases in weight, waist circumference, and BMI were noted in both phases vs baseline
Average combined weight loss for both groups over the 3-month intervention was 7.4 pounds (3.5% relative loss, P<0.001)
DPP, Diabetes Prevention Program; mo, month.
Kramer MK, et al. Am J Prev Med. 2009;37:

27. Translating the DPP Into Community Intervention
The DEPLOY Pilot Study
Pilot, cluster-randomized trial
Group-based DPP lifestyle intervention vs brief counseling alone (control) among high-risk adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities
P=0.002
P<0.001
DEPLOY, Diabetes Education & Prevention with a Lifestyle Intervention Offered at the YMCA; DPP, Diabetes Prevention Program; YMCA, Young Men’s Christian Association.
Ackermann RT, et al. Am J Prev Med. 2008;35:

28. Montana CVD and DPP
Mean weight and physical activity min/week among participants by lifestyle intervention session
CVD, cardiovascular disease; DPP, Diabetes Prevention Program.
Amundson HA, et al. Diabetes Educ. 2009;35:

29. Translation of the DPP’s Lifestyle Intervention
Four additional studies utilizing the DPP lifestyle interventions in community settings provided the following findings:
Promising evidence of the prevention of diabetes by significantly decreasing glucose levels and adiposity
Statistically significant improvements in many behavioral outcomes and anthropometrics, particularly at 6 months
Decreased fasting glucose and weight in at-risk African Americans
Approaches that improve recruitment of participants from underserved communities into research, especially research related to chronic disease risk factors
DPP, Diabetes Prevention Program.
Boltri JM, et al. J Natl Med Assoc. 2011;103:
Katula JA, et al. Diabetes Care. 2011;34:
Ruggiero L, et al. Diabetes Educ. 2011;37:
Santoyo-Olsson J, et al. Gerontologist. 2011;51(Suppl 1):S82-93.

30. Prevention of Diabetes: Pharmacotherapy Studies
Prediabetes Management
Prevention of Diabetes: Pharmacotherapy Studies

31. Rate of Conversion to Normal Glucose Tolerance
Pharmacologic Interventions Proven to Delay or Prevent T2DM Development
Intervention
Rate of Conversion to Normal Glucose Tolerance
Metformin (2 trials)
26%-31%
Acarbose (1 trial)
25%
Pioglitazone (1 trial)
48%
T2DM, type 2 diabetes mellitus.
Sherwin RS, et al. Diabetes Care. 2004;27,(Suppl 1): S47-S54.
Eriksson K-F, Lindgärde F. Diabetologia. 1991;34:
Ramachandran A, et al. Diabetologia 2006;49:
Knowler WC, et al. N Engl J Med. 2002;346:
Defronzo RA, et al. N Engl J Med. 2011;364:

32. The Chinese Prevention Study
The Effect of Metformin on the Progression of IGT to Diabetes Mellitus (N=321)
65%
Incidence of Diabetes (%/yr)
Control
Metformin
IGT, impaired glucose tolerance; RRR, relative risk reduction.
Yang W, et al. Chin J Endocrinol Metab. 2001;17:

33. Effect of Lifestyle Modification and Metformin on Cumulative Diabetes Incidence The Indian DPP (N=531)
RRR (%)
26.4
P=0.029
28.5
P=0.018
28.2
P=0.022
Incidence (%)
n=136
n=133
n=133
n=129
Control
LSM
MET
LSM & MET
DPP, Diabetes Prevention Program; LSM, lifestyle modification;
MET, metformin; RRR, relative risk reduction.
Ramachandran A, et al. Diabetologia 2006;49:

34. Effect of Acarbose on Reversion of IGT to NGT
The Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM)
P<0.0001
n=241
(35.3%)
Number of Patients
n=212
(30.9%)
Placebo
Acarbose
IGT, impaired glucose tolerance; NGT, normal glucose tolerance.
Chiasson JL, et al. Lancet. 2002;359:

35. DREAM: Rosiglitazone and New-Onset Diabetes or Death
No. at risk Placebo Rosiglitazone
0.6
0.5 1 2 3 4
Follow-up (years)
0.4
0.3
0.2
0.1
0.0
Placebo
Cumulative hazard rate
Rosiglitazone
60%
DREAM: Rosiglitazone prolongs time to occurrence of new-onset diabetes or death
DREAM Trial Investigators. Lancet. 2006;368:

36. Pioglitazone for T2DM Prevention in IGT: ACT NOW
Kaplan–Meier plot of hazard ratios for time to development of T2DM
ACT NOW, Actos NOW for the Prevention of Diabetes;
IGT, impaired glucose tolerance; T2DM, type 2 diabetes mellitus.
Defronzo RA, et al. N Engl J Med. 2011;364:

37. Special Concerns for Thiazolidinedione Use in Patients With Prediabetes
Because of concerns about long-term safety, use of thiazolidinediones should be reserved for higher risk populations and those failing other, lower-risk strategies
Garber AJ, et al. Endocr Pract. 2008;14:

38. Effects of Exenatide and Lifestyle Modification on Body Weight and Glucose Tolerance in Obese Patients With and Without Prediabetes
Patients
N=152, weight / kg, BMI /- 7.0 kg/m2 (IGT or IFG 25%)
Design
24-week randomized controlled trial: exenatide or placebo plus lifestyle intervention
Results:
Exenatide-treated patients lost 5.1 kg from baseline vs 1.6 kg with placebo (P<0.001)
Both groups reduced their daily caloric intake
IGT or IFG normalized at end point in 77% and 56% of exenatide and placebo subjects, respectively
BMI, body mass index; IFG, impaired fasting glucose; IGT, impaired glucose tolerance.
Rosenstock J, et al. Diabetes Care. 2010;33:

39. Medical Weight-Loss Strategies
Orlistat may prevent progression from prediabetes to diabetes
Lorcaserin, a selective serotonin 2C agonist, is indicated for use in obese patients with at least 1 weight-related comorbid condition (eg, hypertension, dyslipidemia, CVD, glucose intolerance, sleep apnea)
Low-dose, immediate-release phentermine and controlled-release topiramate is recommended for obese or overweight patients with weight-related comorbidities such as hypertension, T2DM, dyslipidemia, or central adiposity
CVD, cardiovascular disease; obese, BMI ≥30 kg/m2; overweight, BMI ≥27 kg/m2; T2DM, type 2 diabetes mellitus.
Garber AJ, et al. Endocr Pract. 2008;14:

40. Pharmacologic Weight-Loss Strategies
Drug name
Placebo-subtracted mean % body weight loss from baseline
Patients (N) in clinical program/ patients (n) with diabetes
% of patients losing ≥5% of body weight
Clinical trial withdrawal rates
Orlistat
2.4% (following 4 years of treatment with orlistat 120 mg TID)
7504/321
35.5%-54.8% (following 1 year of treatment with orlistat 120 mg TID)
8.8%
Lorcaserin
3.3% at 52 weeks
6888/510
47.1%
36%-50%
Phentermine/ topiramate) 
3.5%-6.4%
3678/808
45%-70%
31%-40%
LOCF, last observation carried forward.
Orlistat [package insert]. South San Francisco CA; Genentech USA; 2010.
Belviq [package insert]. Woodcliff Lake, NJ; Eisai Inc.; 2012.
Qsymia [package insert]. Mountain View, CA; VIVUS , Inc; 2012.

41. Phentermine/Topiramate and Prevention of Type 2 Diabetes
76.6%
79.7%
Annualized incidence of T2DM
48.6%
88.6%
Garvey TW, et al. Diabetes Care. 2014;37: