To identify predictors of failure with metformin, Dr. Nichols' group evaluated the records of patients treated between 1996 and 2003 at Kaiser Permanente Northwest HMO in Portland, Oregon. They identified 1547 patients with diabetes whose first antihyperglycemic drug was metformin.

They then followed the 1288 patients who achieved an HbA1c < 8% during the first year. They defined secondary failure as the addition or switch to another antihyperglycemic drug after 6 months of treatment with metformin, or the first HbA1c measurement of 8% or higher that occurred during follow-up.

According to their report in the March issue of Diabetes Care, the most important factor predicting long-term success with metformin was the reduction of HbA1c achieved during the first year.

For example, more than four out of five patients whose HbA1c level remained > 7% during the first year regained an Hba1c level > 8%; in contrast, approximately half of those with levels < 7% in the first year kept their level < 8% over time.

Compared with patients who achieved an HbA1c < 6%, those who achieved a level of 6% - 6.9% were 3.29 times more likely to add or switch medication. Those who achieved levels of 7.0 - 7.9% were 6.54 times more likely.

The time to reach a 50% rate of adding/switching drugs was 36 months among those whose best HbA1c was 7% - 7.9%, versus 84 months for those with levels below 6%.

Another important factor predicting metformin failure was weight loss. The authors report that those who needed to add or switch drugs lost a mean of 1.9 kg, compared with an average loss of 5.0 kg among those who remained on metformin monotherapy.