The Diabetes Prevention Program 10 Year follow-up Long-term Follow-up to A Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High Risk The DPP Research Group

Diabetes Prevention Program Outcomes Study Clinics

Study Timeline

  To prevent or delay the development of type 2 diabetes in persons with impaired glucose tolerance (IGT) DPP Primary Goal

Study interventions Eligible participants Randomized Standard lifestyle recommendations IntensiveLifestyle (n = 1079) Metformin (n = 1073) Placebo (n = 1082)

Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Metformin, p<0.001 vs. Placebo) DPP Incidence of Diabetes Risk reduction 31% by metformin 58% by lifestyle

Long-termLong-term Body fat distributionBody fat distribution Family history of diabetesFamily history of diabetes Physical inactivityPhysical inactivity Race/ethnicityRace/ethnicity AgeAge Previous gestational diabetes (GDM)Previous gestational diabetes (GDM) Elevated fasting glucose levelsElevated fasting glucose levels Impaired glucose toleranceImpaired glucose tolerance Risk Factors for Type 2 Diabetes

NEGATIVE CONTROLS FORMER GESTATIONAL DIABETICS Diabetes (%) Follow-up (years) Long-term Outcome of Pregnancy O’Sullivan and Mahan, Diabetes, 1964.

Cumulative Incidence of Diabetes in DPP* – Women with History of GDM Risk reduction vs. placebo 51% by metformin (p=0.006) 55% by lifestyle (p=0.002) Risk reduction vs. metformin 8% by lifestyle (p=0.781) * adjusted for age Years from randomization Cumulative incidence (%) Metformin (n = 110) (n = 110) Placebo (n = 122) Lifestyle (n=117) (n=117)

Keys to DPP Lifestyle Success Weight loss was the key to diabetes prevention Reduction of total calories, especially fat calories Achieving 150 minutes of activity each week

Troglitazone Participants There were fewer Troglitazone participants in DPP (n=585) than in the other groups (n~1000) since recruitment was stopped early Treatment with Troglitazone only lasted for an average of 9 months and therefore the long term effects of Troglitazone on diabetes prevention are not known During the brief period of Troglitazone treatment, development of diabetes was decreased by ~70% compared with Placebo

Bridge Period from DPP to DPPOS Summer Fall 2002 – –All participants continued their DPP treatments – –Metformin participants completed medicine wash-out January - June 2002 – –All DPP participants were offered a 16-session Group Lifestyle Balance Program September 2002 – –Diabetes Prevention Program Outcomes Study begins

Who Joined DPPOS? 3251 DPP participants joined DPPOS 88% of the original DPP participants

DPPOS Goals Diabetes delay or prevention Prevention of diabetes complications such as kidney, eye and nerve problems, and heart disease

DPPOS Treatments Original Placebo group – –HELP classes four times a year Original Metformin group – –Metformin 850 mg twice daily – –HELP classes four times a year Original Lifestyle group – –HELP classes four times a year – –BOOST lifestyle classes twice a year

Weight Change Over Time – Overall DPP Research Group. Lancet. 2009; 374: (Figure 2)

Incidence of Diabetes – Overall DPP Research Group. Lancet. 2009; 374: (Figure 3)

Incidence of Diabetes – Overall DPP Research Group. Lancet. 2009; 374: (Figure 3)

DPP vs. DPPOS Diabetes Rates DPP Research Group. Lancet. 2009; 374: (Figure 4)

Diabetes Development in DPPOS Original Lifestyle participants continue to develop diabetes at the lower rate they developed diabetes during DPP. Original Placebo and Metformin participants have lowered their rate of diabetes development to a similar rate as the Lifestyle group.

DPPOS Diabetes Risk Reduction Delay in diabetes onset after 10 years follow-up: – –4 years for Lifestyle – –2 years for Metformin The lower rate of diabetes development for lifestyle and metformin during DPP means: – –Original Lifestyle participants have a 34% lower risk of diabetes compared to Placebo – –Original Metformin participants have a 18% lower risk of diabetes compared to Placebo

Diabetes Frequency After 10 years 52% of Placebo participants have diabetes 47% of Metformin participants have diabetes 42% of Lifestyle participants have diabetes

Use of Anti-diabetic Medicines DPP Research Group. Lancet. 2009; 374: (Figure 5)

Heart Disease Risk All treatment groups have decreased blood pressure, cholesterol and triglycerides. Lifestyle participants had the same or lower blood pressure and lipid levels over time than other participants with less use of medicines.

DPP/DPPOS Publications Diabetes Prevention Program Public Website www. bsc.gwu.edu/dpp/pps/registry.cgi

DPPOS Future Plans Continued mid-year and annual visits Four HELP classes each year A set of retinal (eye) photos in 2012

Additional DPPOS Treatments Two BOOST campaigns each year for original Lifestyle participants. Metformin participants are asked to continue to take study metformin. DPP troglitazone participants will no longer have clinic visits for outcomes testing.

New Outcomes Measures Cognitive (Memory) Testing Physical Function Testing

Diabetes Outcome Annual fasting plasma glucose (FPG) and 75 gm Oral Glucose Tolerance TestAnnual fasting plasma glucose (FPG) and 75 gm Oral Glucose Tolerance Test – FPG > 126 mg/dL (7.0 mmol/L) or – 2-hr > 200 mg/dL (11.0 mmol/L), – Either confirmed with repeat test Semi-annual FPGSemi-annual FPG – > 126 mg/dL, confirmed

Attendance at 16-session Group Lifestyle Balance Program At least some sessions were attended by: – – 57% by the original Placebo – – 58% by the original Metformin – – 40% by the original Lifestyle

Follow-Up Follow-up from randomization in the DPP to the most recent assessment in the DPPOS:Follow-up from randomization in the DPP to the most recent assessment in the DPPOS: – Median was 10.0 years – IQR was years

Weight Change Over Time – yrs old DPP Research Group. Lancet. 2009; 374: (Figure 2)

Weight Change Over Time – yrs old DPP Research Group. Lancet. 2009; 374: (Figure 2)

Weight Change Over Time – 60+ yrs old DPP Research Group. Lancet. 2009; 374: (Figure 2)

BMI Change Over Time – Overall DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

BMI Change Over Time – yrs old DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

BMI Change Over Time – yrs old DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

BMI Change Over Time – 60+ yrs old DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

DPPOS BMI Change – Overall DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

DPPOS BMI Change – yrs old DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

DPPOS BMI Change – yrs old DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

DPPOS BMI Change – 60+ yrs old DPP Research Group. Lancet. 2009; 374: (Webappendix Figure 1)

DPPOS Incidence of Diabetes – Overall DPP Research Group. Lancet. 2009; 374: (Figure 3)

Incidence of Diabetes – yrs old DPP Research Group. Lancet. 2009; 374: (Figure 3)

Incidence of Diabetes – 60+ yrs old DPP Research Group. Lancet. 2009; 374: (Figure 3)

Normoglyceamia ILSMetforminPlacebo FPG<6.1 and 2-hr<7.8 23%19% FPG<5.6 and 2-hr<7.813%11%10% Data are based on the most recent yearly examination.

Summary (1) Successful long-term weight loss was experienced over the 10-year follow-up in the lifestyle groupSuccessful long-term weight loss was experienced over the 10-year follow-up in the lifestyle group Incidence of diabetes in original placebo and metformin groups was reduced to a similar rate as in the original lifestyle groupIncidence of diabetes in original placebo and metformin groups was reduced to a similar rate as in the original lifestyle group Cumulative incidence of diabetes continues to be lower in the lifestyle group than in the other two groupsCumulative incidence of diabetes continues to be lower in the lifestyle group than in the other two groups

Summary (2) Prevention or delay of diabetes within original lifestyle and metformin groups persists for 10 yearsPrevention or delay of diabetes within original lifestyle and metformin groups persists for 10 years Original lifestyle participants have a 34% risk reduction in diabetes compared to placebo Original metformin participants have a 18% risk reduction in diabetes compared to placebo

Summary (3) Lifestyle and metformin treatment resulted in improved blood pressure measurementsLifestyle and metformin treatment resulted in improved blood pressure measurements All groups had decreased cholesterol and triglyceridesAll groups had decreased cholesterol and triglycerides Lifestyle presented the same or lower blood pressure and lipid levels over time as other groups despite lower use of medicationLifestyle presented the same or lower blood pressure and lipid levels over time as other groups despite lower use of medication

Long-termLong-term Body fat distributionBody fat distribution Family history of diabetesFamily history of diabetes Physical inactivityPhysical inactivity Race/ethnicityRace/ethnicity AgeAge Previous gestational diabetes (GDM)Previous gestational diabetes (GDM) Elevated fasting glucose levelsElevated fasting glucose levels Impaired glucose toleranceImpaired glucose tolerance Risk Factors for Type 2 Diabetes