Dataset Information

Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas and Other Glucose-lowering Therapies for Three Acute Outcomes.

ABSTRACT: Although the glucose lowering effect of dipeptidyl peptidase-4 (DPP4) inhibitors is well established, several potential serious acute safety concerns have been raised including acute kidney injury, respiratory tract infections, and acute pancreatitis. Using the UK-based Clinical Practice Research Datalink (CPRD), we identified initiators (365-day washout period) of DPP4 inhibitors and relevant comparators including initiators of sulfonylureas, metformin, thiazolidinediones, and insulin between January 2007 and January 2016 to quantify the association between DPP4 inhibitors and three acute health events - acute kidney injury, respiratory tract infections, and acute pancreatitis. The associations between drug and study outcomes were estimated using Cox proportional hazard models adjusted for deciles of high-dimensional propensity scores and number of additional glucose lowering agents. After controlling for potential confounders, the risk was not significantly increased or decreased for initiators of DPP4 inhibitors compared to sulfonylureas (hazard ratio (HR) [95% confidence interval (CI)] for acute kidney injury: 0.81 [0.56-1.18]; HR for respiratory tract infections: 0.93 [0.84-1.04]; HR for acute pancreatitis 1.03 [0.42-2.52], metformin (HR for respiratory tract infection 0.91 [0.65-1.27]), thiazolidinediones (HR for acute kidney injury: 1.12 [0.60-2.10]; HR for respiratory tract infections: 1.02 [0.86-1.21]; HR for acute pancreatitis: 1.21 [0.25-5.72]), or insulin (HR for acute kidney injury: 1.40 [0.77-2.55]; HR for respiratory tract infections: 0.74 [0.60-0.92]; HR for acute pancreatitis: 1.01 [0.24-4.19]). Initiators of DPP4 inhibitors were associated with an increased risk of acute kidney injury when compared to metformin initiators (HR [95% CI] for acute kidney injury: 1.85 [1.10-3.12], although this association was attenuated when DPP4 inhibitor monotherapy was compared to metformin monotherapy exposure as a time-dependent variable (HR 1.39 [0.91-2.11]). Initiation of a DPP4 inhibitor was not associated with an increased risk of acute kidney injury, respiratory tract infections, or acute pancreatitis compared to sulfonylureas or other glucose-lowering therapies.

SUBMITTER: Gamble JM

PROVIDER: S-EPMC6181978 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background: Acarbose and dipeptidyl peptidase-4 inhibitors (DPP-4is) have several similarities regarding their efficacy. Assessing the hypoglycemic and weight-loss effects, as well as the tolerability between them at their optimal dosages, could provide a better management of adult type 2 diabetics. Methods: We performed a systematic review and network meta-analysis (NMA) on randomized controlled trials that were identified from the databases of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Conference Proceedings Citation Index, ClinicalTrials.gov, China National Knowledge Infrastructure, Wan Fang, and SinoMed. The trials with 300 mg/day of acarbose or the recommended doses of DPP-4is were the most optimal for our NMA. The mean differences (MD) and relative risk (RR) derived from eligible studies were used. Results: Among the 15,411 obtained potential studies, 13 pair-wise trials and 48 monotherapy studies were included in the meta-analysis and NMA, respectively. DPP-4is had a greater glucose-lowering effect, but a weaker weight-loss effect than acarbose in pair-wise meta-analysis (p < 0.05). However, NMA with 11,877 participants showed that, at their optimal doses, acarbose and DPP-4is had similar glucose-lowering effects on the 2-h postprandial glucose (MD 0.96 mmol/L, 95% credible interval -0.56 to 2.54), HbA1c (0.05%, -0.25 to 0.33), fasting plasma glucose reductions (-0.27 mmol/L, -0.76 to 0.24), and HbA1c < 7.0% target goal achievement (RR 1.33, 0.51 to 3.64). Acarbose was superior to DPP-4is regarding weight loss (MD -1.23 kg, -2.08 to -0.33). Acarbose had more withdrawal, gastrointestinal, and overall adverse events than DPP-4is (p < 0.05), but the differences disappeared after longer treatment (p > 0.05). Conclusions: Acarbose and DPP-4is have similar glucose-lowering effects, but the weight-loss effects of acarbose are superior. Therefore, in the use of the most optimal dosages, overweight/obese type 2 diabetics might benefit more from a treatment with acarbose than DPP-4is.

Project description:IntroductionClinical trials conducted in patients with type 2 diabetes (T2DM) treated with glucose-lowering drugs and examining cardiovascular-related outcomes have yielded mixed results. In this work, we aimed to assess the relative treatment effects of empagliflozin versus sitagliptin and saxagliptin (dipeptidyl peptidase-4 (DPP-4) inhibitors) on cardiovascular-related outcomes in patients with T2DM.MethodsWe conducted a systematic literature review to identify clinical trials assessing cardiovascular-related outcomes for sitagliptin-, saxagliptin-, and empagliflozin-treated patients with T2DM. A network meta-analysis of indirect treatment comparisons was conducted in a Bayesian framework. Hazard ratios (HR) and 95% credible intervals (CrI) were computed for six cardiovascular-related outcomes to estimate the relative efficacies of these agents.ResultsEmpagliflozin showed a statistically significant superiority over saxagliptin (HR 0.60; 95% CrI 0.46-0.80) and sitagliptin (HR 0.60; 95% CrI 0.46-0.79) to reduce the risk for cardiovascular-related mortality. For all-cause mortality, empagliflozin showed a statistically significant risk reduction compared to saxagliptin (HR 0.61; 95% CrI 0.49-0.76) and sitagliptin (HR 0.67; 95% CrI 0.54-0.83). A similar pattern was observed in the risk reduction for hospitalization due to heart failure, where empagliflozin was found to be statistically significantly superior to saxagliptin (HR 0.51; 95% CrI 0.37-0.70) and sitagliptin (HR 0.65; 95% CrI 0.47-0.90). Empagliflozin was not statistically significantly different to sitagliptin and saxagliptin with regard to the risk of a composite endpoint composed of death, stroke or myocardial infarction.ConclusionIn this indirect comparison to the DPP-4 inhibitors saxagliptin and sitagliptin, empagliflozin significantly lowered the risk of cardiovascular-related mortality, all-cause mortality and hospitalizations due to heart failure.FundingBoehringer Ingelheim GmbH.

Dataset Information

Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas and Other Glucose-lowering Therapies for Three Acute Outcomes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets