Contemporary analysis of secondary failure of successful sulfonylurea therapy.

Objective: To revise older estimates of secondary failure that may no longer describe the contemporary pattern of sulfonylurea (SU) monotherapy and to identify predictors of such failure.

Methods: We identified 4,091 patients who achieved hemoglobin A1c (A1C) <8% within 1 year after initiation of SU therapy as their first-ever antihyperglycemic drug after January 1, 1996. The study subjects underwent follow-up until they added or switched antihyperglycemic medication, had A1C > or =8%, or terminated health plan membership or until December 31, 2004. We defined secondary failure by using two separate but overlapping approaches: (1) the addition of or switch to another antihyperglycemic drug after 6 months of SU therapy or (2) the first A1C measurement > or =8.0%.

Results: The level of A1C achieved within 1 year after initiation of SU treatment was the most powerful predictor of secondary SU failure. About 50% of patients whose best A1C was 7.0% to 7.9% added or switched antihyperglycemic drugs within 40 months, whereas it took nearly 60 months for those in the 6.0% to 6.9% A1C category and 74 months in the A1C <6.0% category to reach a 50% failure rate. Similarly, more than half of those patients whose best A1C was 7.0% to 7.9% had an A1C value > or =8% within 24 months, whereas it took nearly 60 months for study subjects in the 6.0% to 6.9% A1C category and 86 months for those in the <6.0% category to have SU failure. Younger age and weight gain were also predictive of failure.

Conclusion: Secondary failure of SU therapy is inversely associated with the level of A1C achieved within the first year of SU monotherapy. Clinicians should quickly consider therapeutic adjustments to lower the A1C level rapidly if initial success is not achieved.