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Dipeptidyl peptidase 4 inhibitor use is associated with a lower risk of incident acute kidney injury in patients with diabetes.

ABSTRACT: Dipeptidyl peptidase 4 inhibitor (DPP4i) use potentially slows the progression of diabetic kidney disease, but its effects on the risk of acute kidney injury (AKI) are unclear. We aimed to assess the association between DPP4i use and incident AKI episodes from a nationally representative cohort in Taiwan.All patients newly diagnosed with diabetes mellitus (DM) between 2008, when DPP4i use was first approved in Taiwan, and mid-2013 were enrolled. Propensity score-matched diabetic DPP4i users, who received DPP4i for at least 90 days, and nonusers were selected. The primary and secondary outcomes were incident AKI and dialysis-requiring AKI during follow-up. Cox proportional hazard analyses were performed to examine the effect of DPP4i on the risk of AKI.We enrolled 923,936 diabetic patients; of these, 83,638 DPP4i users (75.7% sitagliptin, 14.6% vildagliptin, and 9.7% saxagliptin) were propensity score-matched to 83,638 non-users. After an average 3.6-year follow-up, 1.56% and 0.35% of DPP4i users and 2.53% and 0.56% of non-users developed incident AKI and dialysis-requiring AKI, respectively. DPP4i use was significantly associated with lower risk of incident AKI (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.53-0.61) and risk of dialysis-requiring AKI (HR 0.57, 95% CI 0.49-0.66). The risk reduction was consistent regardless of DPP4i type, the presence of chronic kidney disease, the previous acute kidney injury, and age.DPP4i use is associated with reduced risk of mild and severe forms of AKI among patients with incident DM. DPP4i may be an important class of anti-glycaemic agent with reno-protective effects.

SUBMITTER: Chao CT

PROVIDER: S-EPMC5581090 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Dipeptidyl peptidase 4 inhibitor use is associated with a lower risk of incident acute kidney injury in patients with diabetes.

Chao Chia-Ter CT Wang Jui J Wu Hon-Yen HY Chien Kuo-Liong KL Hung Kuan-Yu KY

Oncotarget 20170523 32

<h4>Objectives</h4>Dipeptidyl peptidase 4 inhibitor (DPP4i) use potentially slows the progression of diabetic kidney disease, but its effects on the risk of acute kidney injury (AKI) are unclear. We aimed to assess the association between DPP4i use and incident AKI episodes from a nationally representative cohort in Taiwan.<h4>Materials and methods</h4>All patients newly diagnosed with diabetes mellitus (DM) between 2008, when DPP4i use was first approved in Taiwan, and mid-2013 were enrolled. P ...[more]

PMID: 28881791

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Project description:ImportanceGlucagon-like peptide-1 (GLP-1) receptor agonist use is associated with reduced mortality and improved cardiovascular outcomes in the general population with diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used antidiabetic agents for patients with advanced-stage chronic kidney disease (CKD). The association of these 2 drug classes with outcomes among patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD) is not well understood.ObjectiveTo assess whether use of GLP-1 receptor agonists in a population with diabetes and advanced-stage CKD or ESKD is associated with better outcomes compared with use of DPP-4 inhibitors.Design, setting, and participantsThis retrospective cohort study used data on patients with type 2 diabetes and stage 5 CKD or ESKD obtained from the National Health Insurance Research Database of Taiwan. The study was conducted between January 1, 2012, and December 31, 2018. Data were analyzed from June 2020 to July 2021.ExposuresTreatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors.Main outcomes and measuresAll-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events were compared between patients treated with GLP-1 receptor agonists and patients treated with DPP-4 inhibitors. Propensity score weighting was used to mitigate the imbalance among covariates between the groups.ResultsOf 27 279 patients included in the study, 26 578 were in the DPP-4 inhibitor group (14 443 [54.34%] male; mean [SD] age, 65 [13] years) and 701 in the GLP-1 receptor agonist group (346 [49.36%] male; mean [SD] age, 59 [13] years). After weighting, the use of GLP-1 receptor agonists was associated with lower all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.63-0.98) and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91). Subgroup analysis demonstrated a lower risk of mortality associated with use of GLP-1 receptor agonists compared with DDP-4 inhibitors among patients with cerebrovascular disease (HR, 0.33; 95% CI, 0.12-0.86) than among those without cerebrovascular disease (HR, 0.89; 95% CI, 0.71-1.12) (P = .04 for interaction).Conclusions and relevanceTreatment with GLP-1 receptor agonists was associated with lower all-cause mortality among patients with type 2 diabetes, advanced-stage CKD, and ESKD than was treatment with DPP-4 inhibitors. Additional well-designed, prospective studies are needed to confirm the potential benefit of GLP-1 receptor agonist treatment for patients with advanced CKD or ESKD.

Project description:BackgroundDipeptidyl peptidase-3 (DPP3) is a metallopeptidase which cleaves bioactive peptides, notably angiotensin II, and is involved in inflammation regulation. DPP3 has been proposed to be a myocardial depressant factor and to be involved in circulatory failure in acute illnesses, possibly due to angiotensin II cleavage. In this study, we evaluated the association between plasmatic DPP3 level and outcome (mortality and hemodynamic failure) in severely ill burn patients.MethodsIn this biomarker analysis of a prospective cohort study, we included severely ill adult burn patients in two tertiary burn intensive care units. DPP3 was measured at admission (DPP3admin) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI).ResultsOne hundred and eleven consecutive patients were enrolled. The median age was 48 (32.5-63) years, with a median total body surface area burned of 35% (25-53.5) and Abbreviated Burn Severity Index (ABSI) of 8 (7-11). Ninety-day mortality was 32%. The median DPP3admin was significantly higher in non-survivors versus survivors (53.3 ng/mL [IQR 28.8-103.5] versus 27.1 ng/mL [IQR 19.4-38.9]; p < 0.0001). Patients with a sustained elevated DPP3 had an increased risk of death compared to patients with high DPP3admin but decreased levels on day 3. Patients with circulatory failure had higher DPP3admin (39.2 ng/mL [IQR 25.9-76.1] versus 28.4 ng/mL [IQR 19.8-39.6]; p = 0.001) as well as patients with AKI (49.7 ng/mL [IQR 30.3-87.3] versus 27.6 ng/mL [IQR 19.4-41.4]; p = 0.001). DPP3admin added prognostic value on top of ABSI (added chi2 12.2, p = 0.0005), Sequential Organ Failure Assessment (SOFA) score at admission (added chi2 4.9, p = 0.0268), and plasma lactate at admission (added chi2 6.9, p = 0.0086) to predict circulatory failure within the first 48 h.ConclusionsPlasma DPP3 concentration at admission was associated with an increased risk of death, circulatory failure, and AKI in severely burned patients. Whether DPP3 plasma levels could identify patients who would respond to alternative hemodynamic support strategies, such as intravenous angiotensin II, should be explored.

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Dipeptidyl peptidase 4 inhibitor use is associated with a lower risk of incident acute kidney injury in patients with diabetes.

Publications

Dipeptidyl peptidase 4 inhibitor use is associated with a lower risk of incident acute kidney injury in patients with diabetes.

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