New research presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain, shows that patients receiving sulfonylureas as first line treatment for type 2 diabetes have higher mortality than those receiving metformin. The researchers, led by Professor Craig Currie, Cardiff University, UK, say that it may no longer be appropriate to offer first line treatment with sulfonylureas as a result of these findings.
Sulfonylureas such as glipizide, gliclazide or glibenclamide are commonly prescribed as first line therapy in developed countries; for example 7% of people with type 2 diabetes in the UK. This class of drugs was first available in the 1950s. Metformin continues to be one of most commonlyt prescribed antidiabetes treatments, and also has been in use since the 1950s. In this study, Professor Currie and colleagues evaluated the comparative risk of all-cause mortality for patients exposed to first-line diabetes monotherapy with either sulfonylureas or metformin.
The researchers extracted data from the retrospective data were extracted from the Clinical Practice Research Datalink (CPRD): a data resource comprising approximately 10% of all patients treated in primary care in the United Kingdom. Patients with type 2 diabetes initiated with first-line, glucose-lowering treatments between 2000 and 2012 were selected. The primary endpoint was all-cause mortality.
The authors performed a matched-cohort study comparing those treated with sulfonylureas (exposed) versus metformin (non-exposed) using the following matching criteria at baseline: age (±2 years), gender, year of index exposure, diabetes duration (±1 year), BMI (±3 kg/m2), serum creatinine (±10 μmol/l) and Hba1c (±1%).
The analysis showed that 76,811 patients were prescribed metformin monotherapy (mean follow-up 3 years), and 15,687 sulfonylureas (mean follow-up 3 years). Using two alternative methods of investigating possible study biases, 2,048 patients were included in each arm of the direct matched cohorts and 8,836 in the propensity matched. The data showed that patients prescribed sulfonylureas were 58% more likely to die from any cause than those prescribed metformin.
Professor Currie concludes: “Mortality was significantly increased in patients prescribed sulfonylureas as first-line, glucose lowering monotherapy, compared with metformin monotherapy. Whilst residual confounding and confounding by indication may remain, this study indicates that treatment with first-line monotherapy with sulfonylureas should be reconsidered.”
Regarding why sulfonylureas might be prescribed as first-line therapy instead of metformin in the first place, Professor Currie concludes: “"Not all general practitioners or other doctors are fully informed about the risks and benefits of commonly used drugs. Failure to identify the higher mortality associated with certain drugs could also be regarded as a failure of the regulatory system."