Caution urged with add-on DPP-4 inhibitors

By Eleanor McDermid

Physicians should be aware of the need to reduce the dose of sulphonylureas when adding dipeptidyl peptidase-4 (DPP-4) inhibitor treatment in patients with Type 2 diabetes, say the authors of a meta-analysis.

Francesco Salvo (University of Bordeaux, France) and co-researchers found that adding a DPP-4 inhibitor increased the likelihood of hypoglycaemia by 52%.

Giving 17 patients a DPP-4 inhibitor on top of a sulphonylurea would result in one additional episode of hypoglycaemia within the first 6 months of use, show the findings published in The BMJ.

"These results clearly highlight the need to respect existing recommendations for dose reduction of sulphonylureas when initiating treatment with DPP-4 inhibitors, and the urgency to determine the efficacy of this measure in minimising the risk of hypoglycaemia", write Salvo et al.

They stress that hypoglycaemia can be a serious adverse event. "Even when not directly life threatening, it is associated with an increased risk of all cause mortality, cardiovascular disease, cardiovascular mortality, and hospital admission."

The meta-analysis included 10 randomised controlled trials with 6546 participants who received sulphonylureas plus either DPP-4 inhibitors or placebo. Most of the studies followed up patients for no more than 6 months; during this time 479 of 4020 patients taking DPP-4 inhibitors had a hypoglycaemic event, as did 169 of 2526 taking placebo, equating to absolute risks of 11.9% versus 6.7%.

Four trials included patients given a low dose of a DPP-4 inhibitor, and these patients had a nonsignificant 33% increased risk of hypoglycaemia. The researchers note that the 95% confidence interval (0.92-1.94) does not exclude an increased risk, but given the significant 66% increased risk with full-dose DPP-4 they say their findings imply a dose response.

DPP-4 manufacturers advise using a full dose of DPP-4 while reducing the sulphonylurea dose, note Salvo and team. But they add that "to what extent this recommendation would lower the number of excess cases of induced hypoglycaemia is unknown."

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