Glucose-lowering agents other than metformin associated with higher mortality in study

Patients undergoing glucose-lowering therapy, with the exception of metformin monotherapy, may have lower 5-year survival rates than matched controls, according to a recent study.

Researchers used Belgian health expenditure records to study the mortality rates of 115,896 patients who, between January 2003 and December 2007, started metformin, sulfonylurea, or insulin as either monotherapy or combination therapy. Results of the retrospective controlled cohort study were published online on Dec. 17, 2015, by the Journal of Clinical Endocrinology & Metabolism.

The study matched participants with control subjects, who were not undergoing glucose-lowering therapy, and followed them until death or for a maximum of 5 years. Researchers also analyzed the effects of age and concomitant use of statins.

Compared to controls matched for age, gender, cardiovascular history, medications (statins and antiplatelet and antihypertensive drugs), and year of start of follow-up, patients on metformin monotherapy did not show significant excess mortality during follow-up, but patients on sulfonylurea or insulin monotherapy had higher mortality rates. Excess mortality was highest in patients on insulin (23.8%), followed by those on sulfonylurea (4.1%).

Patients taking a combination of the drugs also fared worse than controls, with the highest differences in survival occurring when insulin was involved. Excess mortality was 15.6% in those taking all 3 drugs, 12.9% in those taking metformin and insulin, and 3.3% in those taking metformin and sulfonylurea. “The extra mortality risk [of patients on sulfonylurea and insulin] can, at least partially, be explained by the risk profile of the individuals themselves,” the study authors wrote.

In all groups, the intake of statins was associated with reduced mortality rate. Mortality risks were 60% to 80% lower independent of the type of glucose-lowering therapy or presence of cardiovascular history. In fact, patients taking statins in combination with metformin or sulfonylurea monotherapy showed better survival than the general population.

The researchers noted limitations to their study, such as how the large number of subjects introduced the potential for additional confounders. They also noted that using claims data precluded them from controlling for clinical parameters, such as level of glycemic control or modifiable cardiovascular risk factors. The observational study should not be used to directly compare glucose-lowering therapies because “the patients' underlying conditions yield indications for their treatment,” they wrote.