The Diabetes Prevention Program (DPP) was an RCT (conducted 1996-2001) comparing the impact of intensive lifestyle intervention, metformin, and placebo on the development of diabetes mellitus in high-risk patients with impaired glucose regulation. The current research used baseline data from this study to develop risk equations to predict progression to diabetes and regression to normal glucose regulation among individuals who adhere to the interventions, which can be used in clinical practice.
The authors found that adherence to the metformin intervention was associated with reduced risk of progression to diabetes mellitus. The benefit however was strongly associated with baseline risk, and it was only effective in adherent patients who were at higher risk (25% absolute risk reduction in 3-year probability of progression to diabetes mellitus versus placebo, as compared to a <1% absolute risk reduction in the lowest risk quartile).
Risks of progression to diabetes were consistently lower for those adherent to the lifestyle intervention (achieving ≥5% weight loss at 6 months) than among those adherent to metformin (for all risk levels) and the probability of regression to normal glucose regulation was higher. The authors comment that better identification of individuals at low risk of progressing to diabetes mellitus may prevent overtreatment, reduce treatment-related adverse events, and encourage more appropriate resource utilisation.
The NICE Public Health Guideline on the prevention of type 2 diabetes in people at high risk (updated September 2017) recommends that clinical judgement be used on whether (and when) to offer metformin to support lifestyle change for people whose HbA1c or fasting plasma glucose blood test results have deteriorated if:
A discussion of reasoning behind changes made to the guideline (including the recommendation on metformin) notes that lifestyle-change programmes are more clinically and cost effective than metformin in the high-risk population overall and in most subgroups. However metformin is also cost effective when compared with control alone, and therefore the committee agreed that metformin could be used in support of lifestyle change when blood test results have deteriorated despite someone taking part in these programmes or if they can't take part for some reason. They also agreed that metformin could be used for people whose BMI is over 35 when their blood test results have deteriorated because the model showed that metformin is particularly clinically and cost effective for this group.