Metformin is linked to reductions in development of type 2 diabetes, according to data from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS).
The DPP was a randomized controlled trial conducted from 1996 to 2001 that assigned 3,234 adults at high risk for diabetes to receive masked placebo or metformin, 850 mg twice daily, or intensive lifestyle intervention. The trial ended one year early because of demonstrated efficacy of both the metformin and lifestyle intervention arms. Of the surviving DPP cohort, 88% were followed in the DPPOS; those who had been taking metformin continued to do so, while all participants were offered the lifestyle intervention. The DPPOS took place from 2002 to 2013 and looked at long-term effects of metformin and the intensive lifestyle intervention on diabetes prevention, diabetes-associated microvascular complications, and risk factors for cardiovascular disease. Results pertaining to metformin were published online Aug. 2 by Diabetologia as part of a special theme issue.
In the DPP, over an average of 2.8 years of follow-up, patients taking metformin versus placebo had a 31% lower incidence of diabetes while the intensive lifestyle intervention had a 58% lower incidence. The effect of metformin was particularly significant in those who were obese (53% risk reduction for those with a body mass index [BMI] of ≥35 kg/m2 vs. a 3% reduction in those with a BMI of 22 to <30 kg/m2), had a higher fasting glucose level (48% risk reduction for higher values vs. 15% risk reduction for lower values), or had had gestational diabetes (50% risk reduction vs. 14% risk reduction for parous women without gestational diabetes). In the DPPOS, which offered longer-term follow-up, a risk reduction of 18% for diabetes was seen 10 and 15 years after randomization in those assigned to metformin. The differences in incidence rates remained significant throughout follow-up, but the observed diabetes incidence rates during the DPPOS period did not differ significantly between the original randomized groups, the researchers noted.
The researchers discussed several ways in which metformin could prevent or delay diabetes, including an acute pharmacological effect or amelioration of pathophysiology; effects on blood glucose, weight loss, microvascular complications, and cardiovascular disease (CVD) risk factors; and interaction with genetic factors. They also noted that metformin appeared safe in the DPP/DPPOS, with 9.5% of patients taking the drug reporting minor gastrointestinal symptoms versus 1.1% of those assigned to placebo. Vitamin B12 deficiency, meanwhile, was more common in the metformin group than in the placebo group at five years (4.2% vs. 2.3%; P=0.02), but the difference did not remain significant at 13 years (7.4% vs. 5.4%; P=0.12). The authors noted that there have been no reported cases of lactic acidosis in over 15,000 person-years of exposure to metformin in the DPP/DPPOS. Metformin was found to be cost-saving versus placebo over 10 years, the authors noted.
Going forward, the DPP/DPPOS could also be used to investigate whether early use of metformin in patients at high-risk for diabetes affects development of later comorbid conditions, as well as whether the drug has anti-cancer effects, the authors stated. “Looking to the future, understanding whether translation of these findings into routine clinical care improves current trends in the development of diabetes is of critical importance,” they wrote. “The possibility that metformin can further impact additional complications of dysglycaemia that have not yet been investigated remains an exciting area of study.”