March 18, 2019
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Metformin lowers long-term diabetes risk

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Metformin was shown to have long-term protective effects against diabetes development in adults at greatest risk, especially those with higher HbA1c levels and women who have had gestational diabetes, according to findings published in Diabetes Care.

“Whether metformin should be used for diabetes prevention requires a careful balance of benefits and risks,” Marinella Temprosa, PhD, assistant research professor in the department of epidemiology and biostatistics at George Washington University, and colleagues wrote.

These findings were elucidated from a long-term follow-up of the Diabetes Prevention Program (DPP) and the Diabetes Prevention Program Outcomes Study (DPPOS). In the first study, researchers recruited 3,234 adults with impaired glucose tolerance, elevated blood glucose and a BMI of at least 24 kg/m2, who were all categorized as at risk for diabetes, between 1996 and 1999.

Participants were randomly assigned to placebo, a lifestyle intervention or 850 mg metformin twice daily. In 2001, 1,861 participants continued in the DPPOS and were assigned 850 mg metformin twice a day regardless of their initial study group.

In a 15-year follow-up analysis, Temprosa and colleagues evaluated data from the placebo (n = 1,082; mean age, 50.3 years; 69% women) and metformin (n = 1,073; mean age, 50.9 years, 66.2% women) groups. Although oral glucose tolerance tests and fasting plasma glucose were used to diagnose diabetes in the two previous studies, the researchers included diagnosis by HbA1c in post hoc analysis.

At 15 years, the metformin group had lower diabetes incidence rates by 17% compared with placebo (HR = 0.83; 95% CI, 0.73-0.93), based on OGTT and FPG diagnosis, and 36% by HbA1c diagnosis (HR = 0.64; 95% CI, 0.55-0.75).

When OGTT and FPG were used as diagnostic tools, the researchers wrote that participants with higher FPG levels at baseline experienced an even greater effect from metformin (P = .0004). They also noted that metformin lowered diabetes incidence by 41% in women who previously had gestational diabetes (HR = 0.59; 95% CI, 0.42-0.84). In contrast, with HbA1c as the diagnostic marker, there were “comparable beneficial effects … across all of the subgroups,” the researchers wrote.

“Regardless of the means by which diabetes is diagnosed, the long-term effects of metformin on diabetes development in DPP/DPPOS suggest that metformin remains effective in this cohort,” the researchers wrote. “These results should help to prioritize those groups at high risk of developing diabetes who will benefit most from being treated with metformin. The conclusions regarding HbA1c must be considered carefully, as our original eligibility and diabetes development criteria were based on glucose and not HbA1c criteria.” – by Phil Neuffer

Disclosures: Bristol-Myers Squibb and Parke-Davis provided additional funding and material support for DPP. The authors report no other relevant financial disclosures.