No studies have examined the potential benefits of immediate vs. delayed metformin initiation used with an HbA1C treatment threshold of 7%, or established the failure rate in clinical practice. Researchers therefore conducted this observational study to estimate the rate of secondary of metformin monotherapy experienced by unselected patients in a non-research setting who had a documented history of successfully lowering their HbA1C to < 7% with metformin.

The analyses were conducted within a managed care plan using electronic medical records of 1799 type 2 diabetes patients who, between 2004-2006, lowered their HbA1C to < 7% after initiating metformin monotherapy as their first anti-hyperglycaemic drug. Secondary failure was defined as a subsequent HbA1C ≥ 7.5% or the addition or substitution of another anti-hyperglycaemic agent.

The following findings were reported:

• 42% (n=748) experienced secondary failure; the mean failure rate was 17% per year.

• Patients who initiated metformin within 3 months of diabetes diagnosis failed at an age and HbA1C adjusted rate of 12.2% per year, and patients who initiated while HbA1C was < 7% failed at an adjusted rate of 12.3% per year.

• Age, duration of diabetes and HbA1C at initiation were the only factors that predicted secondary failure.

The researchers conclude that their findings show an association between earlier use of metformin and lengthened effectiveness of the drug, possibly due to more effective preservation of beta cell function, but they do acknowledge that these findings are limited by the observational design of the study. They suggest that initiating metformin soon after diabetes diagnosis and while HbA1C is low may improve the durability of metformin efficacy and thus delay the need for therapeutic adjustments and reduce the glycaemic burden associated with treatment failure. They call for further research into whether earlier metformin monotherapy reduces the risk of microvascular and macrovascular complications.