DPPOS: Effect of Regression from Prediabetes to NGR on Long-term Diabetes Risk Reduction

Perreault L, Pan Q, Mather KJ, et al; for the Diabetes Prevention Program Research Group. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: Results from the Diabetes Prevention Program Outcomes Study.
Lancet. 2012;379(9833):2243-2251. 

More data from ADA 2012 are available in our OnsiteInsight® eNewsletter. Click here.  

This report sought to quantify and predict diabetes risk reduction during the long-term follow-up to the Diabetes Prevention Program (DPP; a randomized, double-blind trial of metformin or placebo), the Diabetes Prevention Program Outcomes Study (DPPOS; an open-label extension of metformin and analysis of adverse events, tolerability, and effects of adherence on weight change and waist circumference). (For more information on DPP and DPPOS, see links at the end of this overview to slides in our Slide Library.)  

The current study examined participants who regressed to normal glucose regulation (NGR; defined as FPG <5.6 mmol/L and 2-hr glucose <7.8 mmol/L) at least once on yearly OGTT during the DPP and never met criteria for diabetes diagnosis. Those who regressed to NGR were then compared against those participants who maintained a prediabetes state (defined as FPG 5.6-6.9 mmol/L and 2-hr glucose 7.8-11.0 mmol/L, or both, on yearly OGTT during DPP; never met criteria for diabetes diagnosis), with and without stratification by previous DPP treatment group.  

Seventy-two percent (72%; n=1,990 of total 2,671) of subjects in the DPPOS were included in this analysis: n=736 in the intensive lifestyle intervention group, n=647 in the metformin group, and n=607 in the placebo group. Included subjects had persistent prediabetes or restoration of NGR over 5.7 years of follow-up in DPPOS; any patient who progressed to diabetes during DPPOS was excluded.  

Achievement of NGR status at least once during DPP equated with a 56% reduced risk of diabetes development during DPPOS (HR, 0.44; 95% CI, 0.37-0.55; P<0.0001) and was unaffected by previous treatment group assignment. Risk reduction was associated with the frequency of achieving NGR:

 Number of times NGR achieved in DPPOS  Diabetes risk reduction 
 1  47% (HR, 0.53; 95% CI, 0.42-0.66; P<0.0001) 
 2  61% (HR, 0.39; 95% CI, 0.28-0.56; P<0.0001) 
 3  67% (HR, 0.33; 95% CI, 0.19-0.58; P=0.0001) 
  P values versus participants with remaining diabetes 

Predictors of achieving NGR during DPPOS included:  

  OR (95% CI)  P 
NGR status vs prediabetes  3.01 (2.25-4.02)  <0.0001  
% weight change during DPP  0.78 (0.72-0.84)   <0.0001  
Insulin resistance  1.16 (1.08-1.25)   <0.0001  
Beta-cell function    1.28 (1.18-1.39)   <0.0001 




Increased weight loss (HR, 1.26; 95% CI, 1.15-1.39; P<0.0001) during DPP and increased BMI (HR, 1.14; 95% CI, 1.05-1.25; P=0.0021) at the beginning of DPPOS adversely affected diabetes risk in DPPOS. Higher beta-cell function (HR, 0.80; 95% CI, 0.71-0.89; P<0.0001) and insulin sensitivity (HR, 0.83; 95% CI, 0.74-0.94; P=0.0001) were protective. Previous DPP treatment group assignment did not have an effect on risk reduction in DPPOS among those who attained NGR.  


July 2012 

 This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest. 

Related content: 

OnsiteInsight® eNewsletter: ADA 2012 

DPPOS Substudy: Effect of Regression from Prediabetes to NGR on Diabetes Risk 

DPPOS Substudy: NGR Status and Risk Reduction 

DPPOS Substudy: NGR Predictors During DPPOS 

DPPOS Substudy: Additional Outcomes 

Last Modified: 11/15/2013