Caution urged with add-on DPP-4 inhibitors

May 5 2016

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."

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.