STUDY SUMMARY
No mortality benefit from metformin or lifestyle modification
This secondary analysis evaluated mortality outcomes for patients at risk for T2D who were part of the DPP trial and then were followed long term in the Diabetes Prevention Program Outcomes Study (DPPOS).1 The initial DPP trial included 3234 adult patients at high risk for T2D (defined as having a BMI ≥ 24; an FPG of 95-125 mg/dL; and a 2-hour glucose level of 140-199 mg/dL). Participants were randomized into groups receiving either intensive lifestyle intervention (which focused on achieving ≥ 150 min/wk of exercise and ≥ 7% body weight loss), metformin 850 mg twice daily, or placebo twice daily; the latter 2 groups also received standard exercise and diet recommendations. Mean age was 51 years, mean BMI was 34, and 68% of participants were female.
At the conclusion of the initial 5-year trial, treatment was unmasked and 86% of the patients continued to be followed for long-term outcomes. Patients in the lifestyle group were offered semiannual lifestyle reinforcement, while the metformin group continued to receive the twice-daily 850-mg dose unless a contraindication developed. If FPG levels increased to ≥ 140 mg/dL in the DPP study, or A1C increased to ≥ 7% in the DPPOS, study metformin was discontinued and management of the patient’s diabetes was transferred to their health care provider. By the end of the DPPOS, 53% of patients in the lifestyle group and 55% in the metformin group had progressed to T2D, compared with 60% in the placebo group (P = 0.003).
After a median 21-year follow-up interval, the investigators collected data on cause of death for patients and evaluated hazard ratios (HRs) for overall and cause-specific mortality. In total, 14% of the participants died, with no statistically significant difference in rates between the 3 groups. Cancer (37%) was the leading cause of death in all groups, followed by cardiovascular disease (CVD; 29%).
Compared with the placebo group, patients taking metformin did not have a decreased rate of overall mortality (HR = 0.99; 95% CI, 0.79-1.25), mortality from cancer (HR = 1.04; 95% CI, 0.72-1.52), or mortality due to CVD (HR = 1.08; 95% CI, 0.70-1.66). Similarly, compared with the placebo group, lifestyle intervention did not decrease overall mortality (HR = 1.02; 95% CI, 0.81-1.28), mortality from cancer (HR = 1.07; 95% CI, 0.74-1.55), or mortality due to CVD (HR = 1.18; 95% CI, 0.77-1.81). Results were similar when adjusted for other factors, including out-of-study metformin use, T2D status and duration, BMI change, and other cardiovascular risk factors.
WHAT’S NEW
Long-term data clarifylimits to interventions’ utility
This study looked at long-term follow-up data on mortality outcomes for patients with prediabetes treated with metformin or lifestyle intervention. Although these interventions did support weight loss, reduce the incidence of T2D, and lower cardiovascular risk factors (eg, hypertension, dyslipidemia), the comorbidity benefits did not affect risk for all-cause or cause-specific mortality, which were similar between the treatment and placebo groups.
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