The main TECOS trial1 demonstrated absolute neutrality for CV complications when sitagliptin, a DPP-4 inhibitor, was added to background glucose-lowering therapy in high-risk patients with type 2 diabetes. These results were expected, given the relatively short duration of the trial (about 3 years) and the low likelihood for this type of drug – without major benefits on CV risk factors – to affect atherosclerosis-related endpoints that quickly.
appeared to be in patients with elevated levels of natriuretic peptides at baseline, prior heart failure, or chronic kidney disease. This finding was perplexing as there was zero suspicion of any such effect from dozens of studies involving the DPP-4 inhibitors previously published. Another DPP-4 inhibitor, alogliptin, had been studied in ACS patients in the EXAMINE trial4, also published around the time of SAVOR-TIMI 53. Here, alogliptin, also neutral on MACE, was associated with a numerically higher number of heart failure events but this did not achieve statistical significance. So, the TECOS data were anxiously awaited. Ultimately, there was absolutely no hint of a heart failure risk with sitagliptin—good news for patients taking and clinicians prescribing this DPP-4 inhibitor.
with saxagliptin remain a mystery, at least to me.
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2. Scirica BM, Bhatt DL, Braunwald E, et al; for the SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-1326.
Van der Werf F, Armstrong P. Trial evaluating cardiovascular outcomes with sitagliptin in patients with type 2 diabetes: TECOS. Presented at ESC Congress 2015. London, England, UK. Abstract 3147.