Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation

Abstract

Objective: Both lifestyle and metformin interventions can delay or prevent progression to type 2 diabetes mellitus (DM) in people with impaired glucose regulation, but there is considerable interindividual variation in the likelihood of receiving benefit. Understanding an individual's 3-year risk of progressing to DM and regressing to normal glucose regulation (NGR) might facilitate benefit-based tailored treatment.

Research design and methods: We used the values of 19 clinical variables measured at the Diabetes Prevention Program (DPP) baseline evaluation and Cox proportional hazards models to assess the 3-year risk of progression to DM and regression to NGR separately for DPP lifestyle, metformin, and placebo participants who were adherent to the interventions. Lifestyle participants who lost ≥5% of their initial body weight at 6 months and metformin and placebo participants who reported taking ≥80% of their prescribed medication at the 6-month follow-up were defined as adherent.

Results: Eleven of 19 clinical variables measured at baseline predicted progression to DM, and 6 of 19 predicted regression to NGR. Compared with adherent placebo participants at lowest risk of developing diabetes, participants at lowest risk of developing diabetes who adhered to a lifestyle intervention had an 8% absolute risk reduction (ARR) of developing diabetes and a 35% greater absolute likelihood of reverting to NGR. Participants at lowest risk of developing diabetes who adhered to a metformin intervention had no reduction in their risk of developing diabetes and a 17% greater absolute likelihood of reverting to NGR. Participants at highest risk of developing DM who adhered to a lifestyle intervention had a 39% ARR of developing diabetes and a 24% greater absolute likelihood of reverting to NGR, whereas those who adhered to the metformin intervention had a 25% ARR of developing diabetes and an 11% greater absolute likelihood of reverting to NGR.

Conclusions: Unlike our previous analyses that sought to explain population risk, these analyses evaluate individual risk. The models can be used by overweight and obese adults with fasting hyperglycemia and impaired glucose tolerance to facilitate personalized decision-making by allowing them to explicitly weigh the benefits and feasibility of the lifestyle and metformin interventions.

Trial registration: ClinicalTrials.gov NCT00004992.

© 2017 by the American Diabetes Association.

Figures

Figure 1

Consort diagram.

Figure 2

A: Calibration curves for progression to DM. Black dots represent deciles of risk for progression to DM.. B: Calibration curves for regression to NGR. Black dots represent deciles of risk for regression to NGR. P values are for D’Agostino and Nam (12) χ2 statistics.

Figure 3

A: Predicted 3-year probabilities of progressing to DM in adherent participants by quartile of risk of developing DM if participants had been assigned to the placebo intervention. B: Predicted 3-year probabilities of regressing to NGR in adherent participants by quartile of risk of developing DM if participants had been assigned to the placebo intervention.