Renal impairment has ramifications for sulphonylurea use
medwireNews: A large study of patients in general practice shows that the risk of hypoglycaemia associated with sulphonylurea use is highest in patients with impaired renal function.
The analysis involved 120,803 patients with Type 2 diabetes identified in the UK Clinical Practice Research Datalink database 2004–12. It showed that, over an average follow-up lasting 3.7 years, patients using sulphonylurea monotherapy were a significant 2.50-fold more likely to have a hypoglycaemic episode than those using metformin monotherapy.
The elevated risk was present in patients with preserved renal function (estimated glomerular filtration rate [eGFR] ≥60 mL/min per 1.73 m2), at a 2.04-fold increase. But it was higher still in patients with reduced renal function, at 2.69- and 4.96-fold increases for those with an eGFR of 30–59 and less than 30 mL/min per 1.73 m2, respectively.
These associations were independent of factors including age, gender, body mass index, cardiovascular disease, chronic heart failure and use of loop diuretics, note Frank de Vries (Maastricht University Medical Centre, the Netherlands) and study co-authors.
A particularly high risk of hypoglycaemia was also observed among users of glibenclamide, who had a 7.48-fold increased risk compared with metformin users. But against the researchers’ expectations, the hypoglycaemia risks associated with the other types of sulphonylureas were similar to each other, with no advantage for gliclazide, despite it being first-choice sulphonylurea in many countries because of a presumed lower risk of hypoglycaemia.
The reported lower hypoglycaemia risk comes from clinical trials, including a meta-analysis, but the team says that “as is often the case, participants in randomised controlled trials may not be representative of the general population with type 2 diabetes receiving sulphonylureas in clinical practice”.
They therefore suggest that their real-world findings could prove important. “This result could greatly impact the current clinical decision making for diabetes care, and should therefore be further assessed, particularly in relation to renal function”, write de Vries et al in The BMJ.
Another finding that surprised the team was the lack of difference in the hypoglycaemia risk associated with sulphonylureas with active versus inactive metabolites. “Because of the mechanism of action, we expected sulphonylureas with active metabolites to show an increased risk, yet found no conclusive evidence of this”, they say.
The hypoglycaemia risk was increased 2.91-fold for active metabolites (glimepiride, glibenclamide) and 2.46-fold for inactive metabolites (glipizide, tolbutamide, gliclazide). However, the researchers note that many of the hypoglycaemic episodes among patients with impaired renal function occurred in those taking sulphonylureas with inactive metabolites, “limiting comparisons with active metabolites.”
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