For sulfonylureas, the hits keep coming, but so far they remain standing.
I’ve run into several diabetes experts over the past few weeks who touted the apparent downside of using a sulfonylurea drug such as glipizide for treating patients with type 2 diabetes. For several years now, conventional wisdom has regarded sulfonylureas as the second-line oral agent – because of their efficacy, long track record, and availability as low-cost generics – to use after metformin for patients with type 2 diabetes who need drug treatment for hyperglycemia.
But in September, at the European Society of Cardiology Congress, Swedish cardiologist Dr. Lars Rydén and British diabetologist Dr. Peter Grant both spoke to me with concern about the clinical consequences of the hypoglycemia episodes triggered by sulfonylureas.
A few weeks later, at the Congress of the European Association for the Study of Diabetes, British pharmacoepidemiologist Craig Currie and his associates presented observational data from well over 100,000 British residents who received oral drug treatment for type 2 diabetes and showed a statistically significant, roughly 50% boost in all-cause mortality over the course of 3 years in those treated with a sulfonylurea, compared with other oral drugs.
In addition to calling for an "urgent" reassessment of the safety of sulfonylureas, Prof. Currie said that he considers pioglitazone, available as a U.S. generic since last year, the most attractive oral drug option following metformin on the basis of its safety record, efficacy, and affordability.
But others are not so quick to pull the plug on sulfonylureas. I posed the question at EASD to Dr. Michael Nauck, a German diabetes expert, who cited the good safety and efficacy performance of sulfonylureas in big trials such as the UKPDS, and said that a decision on the drug class will need to wait until data are available from the CAROLINA trial, which is comparing the sulfonylurea glimepiride and the DPP4 inhibitor linagliptin in about 6,000 patients at more than 600 worldwide centers. Unfortunately those data are not expected for another 5 years. The researchers who designed the CAROLINA trial have said that they see this study as a major test of the cardiovascular safety of sulfonylurea drugs.
In addition to no signals of harm in big trials, the observational data that have tarred the sulfonylurea class, like the findings Prof. Currie reported, are vulnerable to unidentified biases from confounding factors, Canadian pharmacoepidemiologist Dean Eurich told me at EASD. Despite that, Dr. Eurich agreed that sentiment today is running against the sulfonylureas, which also usually cause weight gain and show a decline in their glycemic benefit over time. Plus, he underscored the clear risk that sulfonylurea treatment poses for causing hypoglycemia. "I think the trend is not to use sulfonylureas as much," he told me.
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