Prediabetes: Management

Transcript Prediabetes: Management

Prediabetes

Management

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;14:933-946.

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;14:933-946.

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.

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;14:933-946.

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;14:933-946.

Lifestyle Intervention in Prediabetes

Persons with prediabetes should reduce weight by 5% to 10%, with long-term maintenance at this level • A program of regular moderate-intensity physical activity for 30-60 minutes daily, at least 5 days a week, is recommended A diet that includes caloric restriction, increased fiber intake, and (in some cases) carbohydrate intake limitations is advised.

Garber AJ, et al.

Endocr Pract

. 2008;14:933-946.

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

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 68% 60% 55% Tried to lose or control weight Reduced dietary fat or calories Increased physical activity or exercise 42% All 3 CDC.

MMWR Morb Mortal Wkly Rep

. 2008;57:1203-1205.

11 Prediabetes Management

PREVENTION OF DIABETES: LIFESTYLE STUDIES

12 Prevention of T2DM: Selected Lifestyle Modification Trials

Study

Diabetes Prevention Program Diabetes Prevention Study Da Qing

Country

USA Finland China

3234

Baseline BMI (kg/m 2 )

34.0

Intervention period (years)

2.8

RRR (%)

58 523 577 31 25.8

4 6 39 51

NNT

21 22 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;346:393-403. Eriksson J, et al.

Diabetologia

. 1999;42:793-801.

Li G, et al.

Lancet

. 2008;371:1783-1789. Lindstrom J, et al.

Lancet

. 2006;368:1673-1679.

13 12 10 8 2 0 6 4

T2DM Incidence in the Diabetes Prevention Program

58%

4,8

Intensive lifestyle intervention* (n=1079) 31%

7,8

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;346:393-403.

Effect of Age on Incidence of T2DM in the DPP

14 12 10 2 0 8 6 4 11,6 6,7 25-44

48%

6,2 10,8 7,6 45-59

Age (years) 59%

4,7 10,8 9,6 ≥60

71%

3,1 Placebo Metformin Lifestyle *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;346:393-403.

Effect of Weight on T2DM Incidence in the DPP

6 4 2 0 16 14 12 10 8 9 8,8

65%

3,3 8,9 7,6

61%

3,7 22 to <30 30 to <35

BMI (kg/m 2 )

14,3 7,0 ≥35

51%

7,3 Placebo Metformin Lifestyle *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;346:393-403.

10-Year Weight Loss in the DPP Outcomes Study

0 1 2 3 4 5 Years 6 7 8 9 10

DPP, Diabetes Prevention Program; T2DM, type 2 diabetes mellitus.

DPP Research Group.

Lancet

. 2009;374:1677-1686.

10-Year Incidence of T2DM in the DPP Outcomes Study

Placebo Metformin Lifestyle

0 1 2 3 4 5 Years 6 7 8 9 10

DPP, Diabetes Prevention Program; T2DM, type 2 diabetes mellitus.

DPP Research Group.

Lancet

. 2009;374:1677-1686.

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;374:1677-1686.

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;93:4774-4779.

T2DM Prevention in Women With a History of GDM:

Ratner RE, et al.

J Clin Endocrinol Metab

. 2008;93:4774-4779.

The Finnish Diabetes Prevention Study: Lifestyle Modifications

-3 -4 -5 -6 0 -1 -2 Control (n=250) Weight (kg) Waist (cm) Diet intervention (n=256) SBP (mm Hg) DBP (mm Hg)

<0.001

=0.007

=0.02

DBP, diastolic blood pressure; SBP, systolic blood pressure.

Tuomilehto J, et al.

N Engl J Med

. 2001;344:1343-1350.

The Finnish Diabetes Prevention Study: Lifestyle Modifications

Control (n=250) Diet intervention (n=256) 10 0 -10 -20 -30 -40

<0.001

FPG

(mg/dL)

=0.003

2-h PG

(mg/dL)

Fasting insulin

(mg/mL)

=0.001

2-h insulin

(  g/mL) DBP, diastolic blood pressure; SBP, systolic blood pressure.

Tuomilehto J, et al.

N Engl J Med

. 2001;344:1343-1350.

23 The Finnish Diabetes Prevention Study: Cumulative Incidence of Diabetes Over 4 Years Control (n=250) 78 Diet intervention (n=256) 80 60 40 20 0

58%

32 DBP, diastolic blood pressure; SBP, systolic blood pressure.

Tuomilehto J, et al.

N Engl J Med

. 2001;344:1343-1350.

Da Qing: Cumulative Incidence of Diabetes at 6-Year Evaluation

Patients with IGT (N=577) Total Lean Overweight 100 90 80 70 60 50 40 30 20 10 0 65,9 60 72,3 Control 47,1 38,2 48 Diet 44,2 26,3 51,2 44,6 34,8 52,5 Exercise Diet + Exercise IGT, impaired glucose tolerance.

Pan XR, et al.

Diabetes Care

. 1997;20:537-544.

Cumulative T2DM Incidence During Follow-up in the Chinese Da Qing Diabetes Prevention Study 25 CI, confidence interval; DPP, Diabetes Prevention Program; T2DM, type 2 diabetes mellitus.

Li G, et al.

Lancet

. 2008;371:1783-1789.

Group Lifestyle Balance Program Intervention University of Pittsburgh Primary Care Practice and Diabetes Prevention Support Center 70 60 50 40 30 20 10

Weight Loss Achieved

0 Phase 1 Post (n=51) Phase 2 Post (n=42) Weight Loss > 3.5% Completers Both phases (n=67) Weight Loss > 5% Phase 2 6 mo Phase 2 12 mo Weight Loss >7% • 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,

<0.001) 26 DPP, Diabetes Prevention Program; mo, month.

Kramer MK, et al.

Am J Prev Med

. 2009;37:505-511.

Translating the DPP Into Community Intervention

The DEPLOY Pilot Study -5 -10 -15 -20 15 10 5 0 -25 Standard (4-6 months) Standard (12-14 months) DPP (4-6 months) DPP (12-14 months) 11,8 6

<0.001

-21,6

=0.002

-13,5 • 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 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;35:357-363.

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;35:209-223.

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;103:194-202.

Katula JA, et al.

Diabetes Care

. 2011;34:1451-1457. Ruggiero L, et al.

Diabetes Educ

. 2011;37:564-572. Santoyo-Olsson J, et al.

Gerontologist

. 2011;51(Suppl 1):S82-93.

30 Prediabetes Management

PREVENTION OF DIABETES: PHARMACOTHERAPY STUDIES

31 Pharmacologic Interventions Proven to Delay or Prevent T2DM Development

Intervention

Metformin (2 trials) Acarbose (1 trial) Pioglitazone (1 trial)

Rate of Conversion to Normal Glucose Tolerance

26%-31% 25% 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;34:891-898.

Ramachandran A,

et al

Diabetologia

2006;49:289-297.

Knowler WC, et al.

N Engl J Med

. 2002;346:393-403.

Defronzo RA, et al.

N Engl J Med.

2011;364:1104-15.

The Chinese Prevention Study

2 0 6 4 14 12 10 8

The Effect of Metformin on the Progression of IGT to Diabetes Mellitus (N=321)

11,6

65%

4,1

Control Metformin

IGT, impaired glucose tolerance; RRR, relative risk reduction.

Yang W, et al.

Chin J Endocrinol Metab.

2001;17:131-136.

33 30 20 10 0 60 50 40

Effect of Lifestyle Modification and Metformin on Cumulative Diabetes Incidence The Indian DPP (N=531) 55.0

n=136 Control 28.5

P=0.018

RRR (%) 26.4

P=0.029

n=133 LSM 28.2

P=0.022

n=133 n=129 MET LSM & MET

DPP, Diabetes Prevention Program; LSM, lifestyle modification; MET, metformin; RRR, relative risk reduction.

Ramachandran A,

et al

Diabetologia

2006;49:289-297.

34 250 240 230 220 210 200 Effect of Acarbose on Reversion of IGT to NGT

The Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM)

<0.0001

n=241 (35.3%) n=212 (30.9%) Placebo Acarbose

IGT, impaired glucose tolerance; NGT, normal glucose tolerance.

Chiasson JL, et al.

Lancet.

2002;359:2072-2077.

DREAM: Rosiglitazone and New Onset Diabetes or Death

0.6

0.5

0.4

0.3

0.2

0.1

0.0

0 No. at risk Placebo Rosiglitazone 2634 2635 1 2470 2538 2 Follow-up (years) 3 2150 2414 1148 1310 Placebo 60% Rosiglitazone 4 177 217 DREAM Trial Investigators.

Lancet

. 2006;368:1096-1105.

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;364:1104-1115.

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;14:933-946.

38 Effects of Exenatide and Lifestyle Modification on Body Weight and Glucose Tolerance in Obese Patients With and Without Prediabetes • Patients – N=152, weight 108.6 +/- 23.0 kg, BMI 39.6 +/- 7.0 kg/m 2 (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 (

<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;33:1173-1175.

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/m 2 ; overweight, BMI ≥27 kg/m 2 ; T2DM, type 2 diabetes mellitus.

Garber AJ, et al.

Endocr Pract.

2008;14:933-946.

Pharmacologic Weight-Loss Strategies

Drug name

Orlistat Lorcaserin Phentermine/ topiramate)

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

2.4% (following 4 years of treatment with orlistat 120 mg TID) 3.3% at 52 weeks 7504/321 6888/510 35.5%-54.8% (following 1 year of treatment with orlistat 120 mg TID) 47.1% 8.8% 36%-50% 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.

Phentermine/Topiramate and Prevention of Type 2 Diabetes

Placebo Phen/TPM 7.5/46 3 2 1 0 5 4 7 6 3,5

48.6%

1,8

88.6%

0,4 Prediabetes 6,4 Phen/TPM 15/92

76.6%

1,5

79.7%

1,3 Metabolic syndrome Garvey TW, et al.

Diabetes Care

. 2014;37:912-921.