“Hypoglycemia may contribute to the increased CVD risk associated with sulfonylureas,” Dr. Eriksson suggested. He concluded that the results of ongoing and future randomized trials would be important in order to understand the cardiovascular risk associated with sulfonylureas better and try to figure out any underlying mechanisms.
Dr. Raz Itamar, head of the diabetes unit at Hadassah Medical Center in Jerusalem, chaired the session during which all these study findings were presented and provided a general comment in an interview on why the cardiovascular safety of sulfonylureas was a particular issue that these studies looked at.
He noted that a study performed in the United States in the 1970s had raised suspicion that there might be an increased cardiovascular risk associated with the sulfonylureas, but the current concerns really started with findings from the UKPDS [United Kingdom Prospective Diabetes Study] and the Women’s Health Study (WHS), for example.
“In the UKPDS, patients who were on metformin and a sulfonylurea demonstrated a doubling in the cardiovascular event rate,” Dr. Itamar said, adding that the WHS data also showed a doubling of the risk.
There is a lack of head-to-head, randomized, controlled data, he emphasized and commented that there were many limitations to the analyses presented at the session. These included the small sample sizes and short duration of follow-up, among others. There is also evidence in the literature suggesting that the cardiovascular risk of individual sulfonylureas may be different. So the results need to be reviewed with caution, he advised.
“As a clinician, I try to give a sulfonylurea which seems to have a safer cardiovascular profile, like glimepiride and gliclazide,” Dr. Itamar said. He noted that there was a randomized controlled trial currently recruiting a projected 6,000 patients that would compare glimepiride with a DPP-4 inhibitor directly for several years that should provide additional and much needed information on the cardiovascular safety of sulfonylureas.
Merck UK funded the systematic review and meta-analysis. AstraZeneca supported the CREST study and the sulfonylureas versus DPP4 inhibitor comparison study. Dr. Bain disclosed he had received honoraria, teaching, and research sponsorship or grants from multiple pharmaceutical companies including Merck Sharp & Dohme and AstraZeneca. Dr. Wilke did not report his disclosures. Dr. Eriksson disclosed receiving research grants or honoraria from AstraZeneca and Merck Sharp & Dohme, among others, and that he had previously been an employee of AstraZeneca. Dr. Itamar did not report having any relevant disclosures.