Objective: To systematically evaluate the effect of DPP-4 inhibitors on hypoglycaemia risk in patients with T2DM.
Methods: We searched MEDLINE, Embase, the Cochrane Library and ClinicalTrials.gov to 20 November 2015. We identified and reviewed randomized controlled trials (RCTs) assessing the safety of DPP-4 inhibitors versus placebo or other anti-diabetic drugs in T2DM patients. We estimated odds ratios (OR) with 95% confidence intervals (CI) for hypoglycaemia through network meta-analysis.
Results: We included 130 RCTs with 17 treatments: nine DPP-4 inhibitors (alogliptin, anagliptin, dutogliptin, gosogliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, vildagliptin), five traditional anti-diabetic drugs (insulin, metformin, sulfonylurea, thiazolidinedione, α-glucosidase inhibitors), two more recent drugs (glucagon-like peptide-1 receptor agonists, sodium/glucose cotransporter inhibitors) and placebo. We found: significantly reduced risk of hypoglycaemia for saxagliptin (OR 0.26, 95% CI 0.08 to 0.83) and vildagliptin (OR 0.32, 95% CI 0.11 to 0.90) versus insulin; and alogliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and vildagliptin versus sulfonylurea (OR range 0.10 (95% CI 0.03 to 0.31) to 0.15 (95% CI 0.10 to 0.22)); but significantly increased risk for sitagliptin versus thiazolidinedione (OR 2.10, 95% CI 1.11 to 3.97). According to ranking probabilities, from the nine DPP-4 inhibitors, teneligliptin had the maximum probability of the lowest risk of hypoglycaemia, while anagliptin had the maximum probability of the highest risk.
Conclusion: Most DDP-4 inhibitors are likely to have reduced risk of hypoglycaemia in T2DM patients when compared with insulin or sulfonylurea, while sitagliptin was found to have increased risk when compared to thiazolidinedione. These results indicate the different effects of DPP-4 inhibitors on hypoglycaemic risk and the need for further specific research.
Funding received: This article was supported by National Natural Science Foundation of China (81302508).
Correspondence: Prof Siyan Zhan, Email: firstname.lastname@example.org; Prof Feng Sun, Email: email@example.com