Purpose: A recent pooled analysis of three randomized clinical trialsa suggests that in subjects with type 2 diabetes, the use of sulphonylurea may be associated with increased cardiovascular risks compared to sitagliptin. The magnitude of the differences in these cardiovascular risks may be greater than those predicted by the risk equations/algorithms of the United Kingdom Prospective Diabetes Studies (UKPDS) outcomes modelb, commonly used in public policy reimbursement decisions. The purpose of this study is to evaluate the impact of these potential differences in drug-induced cardiovascular risks, beyond those predicted by the UKPDS through risk-factor modification, in an economic evaluation comparing metformin+sulphonylurea versus metformin+sitagliptin in persons with type 2 diabetes in Sweden.
Methods: We used a previously published simulation modelc, based on the UKPDS Outcomes model, to compare the long-term impact of metformin+sitagliptin and metformin+sulphonylurea on type 2 diabetes and diabetes-related and drug-induced cardiovascular outcomes in Sweden. To simulate differences in drug-induced cardiovascular risk that may not be captured by UKPDS outcomes equations, we modified the risk-equation of two UKPDS-equation-generated cardiovascular events—myocardial infarction (MI), and stroke—by increasing the UKPDS-calculated risk of each event by 0% to 20% in increments of 5% for the sulphonylurea arm only (i.e. increase sulphonylurea relative risk by up to 20%). Risk was increased for both the events separately and jointly, and the incremental cost-effectiveness ratios (ICERs) were computed.
Results: The ICER for metformin + sitagliptin compared to metformin + sulphonylurea as predicted by the UKPDS equation was US$ 26,428 (SEK 179,061). An increase of 20% in UKPDS-calculated relative risk for the sulphonylurea arm for MI, stroke, and MI+stroke (joint) resulted in 25%, 14%, and 34% reductions in ICER (metformin + sitagliptin compared to metformin + sulphonylurea), respectively (Figure 1).
Conclusions: Increasing
the UKPDS-calculated risk of cardiovascular events for the sulphonylurea arm
resulted in a reduction in the ICER for metformin+sitagliptin compared to
metformin+sulphonylurea in Sweden. Differences in drug-induced cardiovascular
risks between sulphonylurea and sitagliptin, beyond those estimated by the
UKPDS risk equations, may impact cost-effectiveness of sitagliptin vs.
sulphonylurea and should be captured in the economic analyses.
References
a Engel et al. 2013. Cardiovascular Diabetology, doi:10.1186/1475-2840-12-3
b Clarke et al. 2007. Diabetologia; 47:1747–1759.
c Chen et al. 2008. doi:10.1111/j.1463-1326.2008.00885.x
