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Eighteen Years After the DPP (Diabetes Prevention Trials)

Apr 6, 2019
 

Author: Steve Freed, R.PH., CDE


What are the long-term effects of metformin on diabetes prevention?

In a follow-up of the Diabetes Prevention Program Outcomes Study (DPPOS), researchers looked at the effects of metformin on diabetes prevention and the subgroups that benefited most over 15 years in the Diabetes Prevention Program.

During the DPP (1996–2001), adults at high risk of developing diabetes were randomly assigned to masked placebo (n = 1,082) or metformin 850 mg twice daily (n = 1,073). Participants originally assigned to metformin continued to receive metformin, unmasked, in the DPPOS (2002–present). Ascertainment of diabetes development was based on fasting or 2-h glucose levels after an oral glucose tolerance test or on HbA1c. Reduction in diabetes incidence with metformin was compared with placebo in subgroups by hazard ratio (HR) and rate differences (RDs).

The results showed that during 15 years of post-randomization follow-up, metformin reduced the incidence by hazard ratio (by HR) of diabetes compared to placebo by 17% or 36% based on glucose or HbA1c levels, respectively. Metformin’s effect on the development of glucose-defined diabetes was greater for women with a history of prior gestational diabetes mellitus (GDM) (HR 0.59, RD −4.57 cases/100 person-years) compared with parous women without GDM (HR 0.94, Rate Difference(RD) −0.38 cases/100 person-years). Metformin also had greater effects, by HR and RD, at higher baseline fasting glucose levels. With diabetes development based on HbA1c, metformin was more effective in subjects with higher baseline HbA1c by RD, with metformin RD −1.03 cases/100 person-years with baseline HbA1c<6.0% (42 mmol/mol) and −3.88 cases/100 person-years with 6.0–6.4%..

Previous analyses of the original DPP data supported a particularly powerful effect of metformin in subgroups defined by higher fasting glucose levels, higher BMI, and a history of GDM, when evaluated by percent risk reduction, i.e., the HR for metformin compared with placebo. These results prompted the American Diabetes Association, among others, to suggest that metformin be considered in the prevention of diabetes in people at high risk. The American Diabetes Association specifically recommended that metformin be considered in those subgroups that it concluded had the greatest relative benefit with metformin in the DPP. This recommendation is further supported by the demonstrated cost savings of metformin in diabetes prevention.

In conclusion from the results, metformin reduces the development of diabetes over 15 years. The subsets that benefitted the most include subjects with higher baseline fasting glucose or HbA1c and women with a history of GDM.

Practice Pearls:

  • Metformin was able to reduce the development of diabetes over 15 years
  • The American Diabetes Association specifically recommended that metformin be considered in those subgroups that it concluded had the greatest relative benefit with metformin in the DPP
  • Using metformin to prevent the diagnosis of diabetes also has demonstrated cost savings in diabetes prevention.

Diabetes Care 2019 Apr; 42(4): 601-608.https://doi.org/10.2337/dc18-1970