Among those who achieve A1C targets with metformin, earlier initiation associated with improved likelihood of sustained treatment success, data indicate

Among individuals with type 2 diabetes who achieve glycemic control with metformin, those who initiate the drug soon after diabetes is diagnosed when A1C is still low are more likely to sustain glycemic control long term, according to data from an observational cohort study. Researchers evaluated rates and predictors of secondary treatment failure in 1,799 patients with type 2 diabetes who were members of Kaiser Permanente Northwest and who achieved an A1C level =7.5% or the...

Among individuals with type 2 diabetes who achieve glycemic control with metformin, those who initiate the drug soon after diabetes is diagnosed when A1C is still low are more likely to sustain glycemic control long term, according to data from an observational cohort study.

Researchers evaluated rates and predictors of secondary treatment failure in 1,799 patients with type 2 diabetes who were members of Kaiser Permanente Northwest and who achieved an A1C level <7% after initiating metformin monotherapy as first-line treatment.

The investigators reviewed A1C values through the end of 2008 (ie, during 2 to 5 years of follow-up) to identify cases of secondary treatment failure, defined as a subsequent A1C level >=7.5% or the addition/substitution of another diabetes drug.

During the follow-up period, 748 patients (42%) experienced secondary treatment failure, yielding a mean annual failure rate of 17%. The study authors noted that this rate is higher than the rates typically reported in clinical trials such as the ADOPT trial, which reported a rate of 4% (with failure defined as a fasting plasma glucose level >180 mg/dL [corresponding to an A1C level of approximately 8%]).

Among the patients who initiated metformin within 3 months of receiving a diabetes diagnosis (40% of the population), the age- and A1C-adjusted annual rate of treatment failure was 12.2% compared with 17.7% to 21.9% among the patients who waited >=4 months to start treatment. Similarly, the adjusted annual rate of treatment failure was 12.3% among the patients who initiated therapy with an A1C level <7% (27% of the cohort) compared with 17.8% to 19.4% among the patients who had higher A1C levels at the start of therapy.

In a multivariable analysis that included 20 possible risk factors for secondary treatment failure, the only significant predictors were a younger age at diagnosis, a greater time from diagnosis to the start of therapy, and a higher A1C level at the start of therapy.

Sensitivity analyses in which the failure threshold was adjusted to either 7% or 8% (from 7.5%) did not change the results, the researchers noted.

Although the authors acknowledged certain limitations to the analysis, many of which could be attributed to its observational design, they concluded that these findings are "consistent with the hypothesis that early initiation of metformin preserves beta-cell function and supports the current American Diabetes Association/European Association for the Study of Diabetes hyperglycemia treatment algorithm, which recommends metformin therapy as soon as type 2 diabetes is diagnosed." (Brown JB, et al. Diabetes Care 2010;33:501-506.)