Spotlight on second-line therapies

Two recent studies considered whether initiation of second-line therapies in patients already taking metformin for type 2 diabetes occurs too soon or too late.


Two recent studies looked at the initiation of second-line therapies in patients already taking metformin for type 2 diabetes.

The first study, published online Sept. 13 by Diabetes Care, was a retrospective cross-sectional analysis of 52,544 patients with type 2 diabetes covered by Aetna between 2010 and 2015. Researchers used claims data to determine what medications patients took. They found that of 22,956 patients who were prescribed a second-line diabetes medication, only 8.2% appeared to be filling prescriptions for metformin at a frequency recommended by guidelines, and 28% showed no evidence of filling a metformin prescription. Because patients using a low-cost generic program to obtain metformin would be missed by this analysis, the researchers also performed sensitivity analyses. They concluded that, at most, only 49.5% of the patients could have been taking metformin as recommended when they were prescribed a second-line medication. Patients who didn't appear to be taking metformin were more likely to be male and more likely to receive insulin or more than one second-line therapy.

“Apparent treatment failures, which may in fact be attributable to nonadherence to guidelines, are common,” the study authors concluded. They noted that data on dispensed prescriptions could be made available to clinicians at the point of care through electronic health record systems and that a variety of electronic interventions could be used to improve adherence to guideline-recommended medications. The study was limited by its design as a retrospective claims-based analysis.

The second study, published by Diabetes, Obesity and Metabolism on Sept. 28 and funded by AstraZeneca, looked retrospectively at 10,256 type 2 diabetes patients who received a second-line therapy between 2011 and 2014 in Germany and the United Kingdom. Researchers found that 28.5% of the patients were discontinuing metformin to switch to another therapy, while the rest received a second-line therapy as an addition to metformin. The patients' baseline HbA1c was 8.68%, and it decreased an average of 1.27% in the six months after the start of a second-line drug. Patients with a higher HbA1c at baseline saw greater decreases in HbA1c on a second-line medication, as did those who initiated second-line therapy within six months of diabetes diagnosis and those who were 70 years of age or older.

The results show that many patients with type 2 diabetes have a high HbA1c level when second-line therapy is initiated, “indicating the need for earlier treatment intensification,” according to the study authors. Another important finding is that about a quarter of patients in the study discontinued metformin therapy, a higher percentage than would be expected if guideline recommendations are being followed, the authors added. The study had a number of limitations, including the assumption that patients adhered to their prescribed medications, the authors noted.