“We would like to stress that this study was not designed to compare different GLAs,” stated Pieter Gillard, PhD, Department of Endocrinology, University Hospitals Leuven, Belgium. “For instance, the background population of patients on metformin is different from patients on a sulfonylurea or insulin. This explains already a part of the survival differences between populations. We cannot, however, exclude that the choice of GLA might have an impact on survival of patients. So, for instance, if a physician can choose between metformin or sulfonylurea, metformin might be the safer choice.”
“Furthermore, this study on a very large patient cohort adds real-life data to the evidence that statins have a beneficial impact on the survival of patients with diabetes,” Dr. Gillard said. “Intake of statins brings survival to a level that is comparable to the general population with similar background.”
Large Retrospective Cohort Study
“We performed a large retrospective cohort study on over 100,000 Belgian patients to map their survival after starting glucose-lowering pharmacotherapy involving metformin, sulfonylurea, and insulin or combinations thereof,” said Dr. Gillard. “We focused on quantifying excess mortality of patients in these study cohorts compared to matched control patients with similar observable characteristics,” but who were not taking glucose lowering agents.
Each case patient with type 1 or type 2 diabetes (n=115,986) was matched to 5 control patients for age, gender, cardiovascular history, and concomitant therapy (ie, antihypertensives, statins and blood platelet aggregation inhibitors). The primary outcome was 5-year survival after the patients began taking a GLA.
“Our results show that excess mortality varies across GLA therapies,” Dr. Gillard said (Table). “Patients starting metformin monotherapy are the only ones that showed no excess mortality compared to their respective controls, while patients starting insulin monotherapy exhibited the largest excess mortality.”
We additionally observed that patients who used statins in combination with GLA therapy have consistently improved survival, compared to patients on GLA therapy but without statins, regardless of a potential history of cardiovascular events prior to starting GLA therapy.
Effects of Age on Mortality
“We have examined the survival of patients starting GLA therapy as a function of age at which therapy is initiated,” Dr. Gillard said. The authors found that 5-year survival rates were lower at any age in patients taking GLAs compared with the general population with the exception of metformin monotherapy.
“Despite the fact that age’s strong and nonlinear influence on survival is hardly surprising, we are the first to accurately capture and visualize this effect, which was enabled by the size of the patient pool,” Dr. Gillard told EndocrineWeb. “We have shown figures depicting 5-year survival after starting GLA therapy at a given age, which provide a useful reference frame for physicians to accurately estimate prognoses for new patients.”
“The study shows that the drugs that different patients with diabetes take can be a signal of their prognosis,” commented Elbert Huang, MD, MPH, FACP, Associate Professor of Medicine, Director Center for Translational and Policy Research of Chronic Diseases, at the University of Chicago. “However, the study does not definitely answer any questions about the mortality effects of diabetes medications.
“It is really important for practitioners to not take any treatment recommendations away from this observational study,” Dr. Huang said. “The findings “primarily raise the stakes for ongoing randomized controlled trials of diabetes medications,” Dr. Huang added.
“When we take care of people with diabetes, it is not unusual for patients to require changes in their medications because the first drug stops controlling blood sugar,” Dr. Huang noted. “A number of open questions remain. What is the best second line drug? What is the best third line drug? What are the patient factors that require modification of treatments?”
February 23, 2016
Claesen M, Gillard P, De Smet F, Callens M, De Moor B, Mathieu C. Mortality in individuals treated with glucose-lowering agents: a large, controlled cohort study. J Clin Endocrinol Metab. 2016;101(2):461-469.