In the DPP and DPP-OS trials, diabetes was prevented or delayed with metformin or ILS when directed at weight loss and increased physical activity…
Previous randomized clinical trials such as the Diabetes Prevention Program and the long-term follow-up trial, the Diabetes Prevention Program Outcomes study, evaluated metformin and an intensive lifestyle (ILS) weight-loss intervention to prevent or delay type 2 diabetes.
In this study, different diagnostic criteria was compared and A1c was evaluated as a risk indicator. HbA1c was used as a predictor of diabetes and as an alternate outcome in both the Diabetes Prevention Program and DPP-outcome study.
There were 3,234 non-diabetic participants with the following risk factors: BMI ≥24 kg/m2, FPG ≥95 mg/dL and <126 mg/dL, and 2hPG ≥140 mg/dL and <200 mg/dL. The participants were randomly assigned to one of three treatment groups: metformin 850 mg twice per day, intensive lifestyle (ILS), or placebo. Diabetes diagnosis was made if FPG was ≥126 mg/dL at a semiannual examination or 2hPG during the annual 75g OGTT if was ≥200 mg/dL, according to ADA criteria. A diagnosis required confirmation on a repeat of the same test. If participants were diagnosed then results were reported to PCP and study was continued unless hyperglycemia worsened to FPG ≥140 mg/dL during DPP or A1c ≥7.0% during DPP-OS.
Of the 3,234 participants only 2,765 participants qualified and were included in the study. The participants were grouped by baseline A1c of <5.5%, 5.5% to <6.0%, or 6.0% to <6.5%. A1c was measured at baseline, 6 months, and 12 months and then annually. The intention-to-treat analysis compared each intervention group with the placebo group on the modified product-limit life-table distribution using the log-rank test statistic. Treatment groups and study time periods were also compared with incidence rates in cases/100 person-years.
The study showed that none of the diabetes risk factors, including A1c and glucose measures, differed among the 3 treatment groups. Results showed that A1c at baseline was a strong predictor of the development of glucose-defined diabetes during the DPP and total follow-up periods. During the DPP and total follow-up periods, the incidence of glucose-defined diabetes was positively related to baseline A1c, and stratified by baseline A1c, the incidence was reduced by metformin versus placebo (P < 0.001) and by intensive lifestyle versus placebo (P < 0.001), and the reduction by intensive lifestyle was greater than that by metformin (P < 0.001).
A1c is recommended for identifying patients at high risk of developing diabetes and as a diabetes diagnostic criterion. The ILS was substantially more effective than metformin in preventing glucose-defined diabetes.
- In the DPP and DPP-OS trials, diabetes was prevented or delayed with metformin or ILS when directed at weight loss and increased physical activity.
- The ILS was substantially more effective than metformin in preventing glucose-defined diabetes.
- If A1c was ≥ 6.5% and had been the outcome, then the study would have concluded that both interventions were similarly effective.
William C. Knowler. “HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial”. Diabetes Care 2015;38:51–58