Forming More Insight on Metformin

Haley Pals, Pharm.D., GuidePoint Pharmacy

Background: The Diabetes Prevention Program (DPP) study aimed to provide more insight on metformin’s role as preventative therapy for type 2 diabetes mellitus (T2DM). Prophylactic use of metformin is currently off-label, however it has been used as a relatively low-risk option in conjunction with lifestyle modification for those at high risk of developing T2DM. 15-year follow-up results from DPP’s initial cohort were recently analyzed in the Diabetes Prevention Program Outcome Study (DPPOS) to build upon existing evidence for prophylactic metformin use.

Purpose: To examine the effects of metformin in diabetes prevention, and to determine which subgroups benefit the most from prophylactic metformin use.

Design: DPP was a randomized placebo-controlled cohort study following participants who were at high risk of developing T2DM. High risk was defined as impaired glucose tolerance, elevated fasting blood glucose, and BMI ≥ 24 kg/m2. Onset of T2DM in those who received metformin 850mg twice daily was compared to those who received placebo. After DPP’s initial follow-up period of 2.8 years, those randomized to metformin continued to receive metformin unblinded. Additional stratification for other risk factors was analyzed to see which groups of participants benefited the most from this preventative therapy. Fifteen years later, researchers reassessed these participants to determine if the positive effects of metformin remained.

Results: DPP and DPPOS both found positive correlation between metformin therapy and prevention of T2DM onset when compared to placebo. The effects were significant in those with higher baseline fasting blood glucose and women with a history of gestational diabetes. In those with a baseline fasting blood glucose of ≥110 mg/dL, there was a significantly lower rate of diabetes development (HR 0.75 [95% CI 0.62-0.90], P=0.0004) compared to those with a lower fasting blood glucose of 95-109 mg/dL (HR 0.83 [95% CI 0.71-0.98], P=0.0004). Metformin’s protective effects were also greater in women with a history of gestational diabetes (HR 0.59 [95% CI 0.42-0.84], P=0.03) than those without (HR 0.94 [95% CI 0.78-1.13], P=0.03).  The incidence of T2DM overall was 17% lower in the metformin group (HR 0.83 [95% CI 0.73-0.93]).

Conclusion: In the short-term and long-term, metformin therapy was effective at reducing the risk of developing T2DM. 

Key Point: These findings further strengthen the American Diabetes Association’s recommendations to prescribe metformin to lower the risk of developing T2DM in patients with elevated fasting blood glucose or prior gestational diabetes. 


  1. Diabetes Prevention Program Research Group. Long-term Effects of Metformin on Diabetes Prevention: Identification of Subgroups That Benefited Most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care. 2019;42(4):601-608.

  2. Standards of Medical Care in Diabetes. Diabetes Care. 2019;42(S1):S1-S193.