Adding DPP-4s to sulfonylureas may increase hypoglycemia risk
The review of 10 randomized controlled trials found 1 excess case of hypoglycemia for every 17 patients in the first 6 months of combined treatment.
Adding dipeptidyl peptidase-4 (DPP-4) inhibitors to sulfonylureas to treat type 2 diabetes was associated with a 50% increased risk of hypoglycemia and with 1 excess case of hypoglycemia for every 17 patients in the first 6 months of treatment, a systematic review and meta-analysis found.
Researchers reviewed 10 randomized controlled trials with at least 50 participants with type 2 diabetes treated with DPP-4 inhibitors and/or sulfonylureas. The cohort included 6,546 participants. Results were published by The BMJ on May 3.
Overall, 4,020 patients received DPP-4 inhibitors (2,096 at full dose, 726 at low dose, and 1,198 at undefined dose) plus sulfonylureas. In this group, 479 developed hypoglycemia (311 at full dose, 67 at low dose, and 101 at undefined dose), for an absolute risk of 11.9%. Another 2,526 patients received placebo plus sulfonylureas, 169 of whom developed hypoglycemia, corresponding to an absolute risk of 6.7%.
The risk ratio of hypoglycemia for DPP-4 inhibitors at any dose plus sulfonylureas versus placebo plus sulfonylureas was 1.52 (95% CI, 1.29 to 1.80), with no evidence of heterogeneity across the trials. The number needed to harm (NNH) was 17 (95% CI, 11 to 30) for a treatment duration of 6 months or less, 15 (95% CI, 9 to 26) for 6.1 to 12 months, and 8 (95% CI, 5 to 15) for more than 1 year. For full-dose DPP-4 inhibitors plus sulfonylureas, the NNH was 13 (95% CI, 8 to 25) for a treatment duration of 6 months or less, 11 (95% CI, 7 to 22) for 6.1 to 12 months, and 7 (95% CI, 4 to 13) for more than 1 year.
When trials with a high risk of detection bias and reporting bias were excluded from the analysis, the pooled risk ratio was 1.40 (95% CI, 1.18 to 1.67). When trials that allowed the use of insulin were excluded, the risk ratio was 1.61 (95% CI, 1.30 to 2.00). When trials in which an apparent imbalance in sex ratio were excluded, the risk ratio was similar to that of the principal analysis (1.52, 95% CI, 1.27 to 1.81).
Even though the effectiveness of reducing sulfonylurea doses has not yet been assessed, the authors wrote, “This potentially represents a huge number of attributable cases worldwide. 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.”