Dataset Information

Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study.

ABSTRACT:

Aims

We compared the new use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP4i) and the risk of cardiorenal disease, heart failure (HF) or chronic kidney disease (CKD), in patients with type 2 diabetes without a history of prevalent cardiovascular and renal disease, defined as cardiovascular and renal disease (CVRD) free, managed in routine clinical practice.

Materials and methods

In this observational cohort study, patients were identified from electronic health records from England, Germany, Japan, Norway, South Korea and Sweden, during 2012-2018. In total, 1 006?577 CVRD-free new users of SGLT2i or DPP4i were propensity score matched 1:1. Unadjusted Cox regression was used to estimate hazard ratios (HRs) for outcomes: cardiorenal disease, HF, CKD, stroke, myocardial infarction (MI), cardiovascular and all-cause mortality.

Results

Baseline characteristics were well balanced between the treatment groups (n = 105?130 in each group) with total follow-up of 187?955 patient years. Patients had a mean age of 56?years, 43% were women and they were indexed between 2013 and 2018. The most commonly used agents were dapagliflozin (91.7% of exposure time) and sitagliptin/linagliptin (55.0%), in the SGLT2i and DPP4i, groups, respectively. SGLT2i was associated with lower risk of cardiorenal disease, HF, CKD, all-cause and cardiovascular mortality; HR (95% confidence interval), 0.56 (0.42-0.74), 0.71 (0.59-0.86), 0.44 (0.28-0.69), 0.67 (0.59-0.77), and 0.61 (0.44-0.85), respectively. No differences were observed for stroke [0.87 (0.69-1.09)] and MI [0.94 (0.80-1.11)].

Conclusion

In this multinational observational study, SGLT2i was associated with a lower risk of HF and CKD versus DPP4i in patients with type 2 diabetes otherwise free from both cardiovascular and renal disease.

SUBMITTER: Birkeland KI

PROVIDER: S-EPMC7756303 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study.

Birkeland Kåre I KI Bodegard Johan J Banerjee Amitava A Kim Dae Jung DJ Norhammar Anna A Eriksson Jan W JW Thuresson Marcus M Okami Suguru S Ha Kyoung Hwa KH Kossack Nils N Mamza Jil Billy JB Zhang Ruiqi R Yajima Toshitaka T Komuro Issei I Kadowaki Takashi T

Diabetes, obesity & metabolism 20200928 1

<h4>Aims</h4>We compared the new use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP4i) and the risk of cardiorenal disease, heart failure (HF) or chronic kidney disease (CKD), in patients with type 2 diabetes without a history of prevalent cardiovascular and renal disease, defined as cardiovascular and renal disease (CVRD) free, managed in routine clinical practice.<h4>Materials and methods</h4>In this observational cohort study, patients were i ...[more]

PMID: 32893440

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Project description:BACKGROUND:Sodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors. METHOD:We conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors. RESULTS:We identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (-?1.0 vs. -?1.1%; P?=?0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (-?1.5 vs. -?1.0 kg; P?=?0.008), SBP (-?2.5 vs. -?0.7 mmHg; P?<?0.001) and ALT values (-?4.1 vs. -?0.0 U/l; P?<?0.001) and smaller declines in eGFR values (-?2.0 vs. -?3.5 ml/min/1.73 m2; P?<?0.001) when compared to DPP4 inhibitors. CONCLUSION:SGLT2 inhibitors had glucose-lowering effects comparable to those of DPP4 inhibitors but more favorable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients' cardio-metabolic disease risks.

Project description:BackgroundSodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients.MethodsWe used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first.ResultsOverall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50-0.73; P?<?0.001]. Subgroup analysis revealed that the use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i across several subgroups including old age, female in gender, the presence of cardiovascular disease, hemoglobin A1c [Formula: see text] 8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i.ConclusionsSGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.

Project description:Introduction: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset cognitive dysfunction in type 2 diabetes mellitus remain unknown. This study aimed to evaluate the effects of the two novel antidiabetic agents on cognitive dysfunction by comparing the rates of dementia between SGLT2I and DPP4I users. Methods: This was a population-based cohort study of type 2 diabetes mellitus patients treated with SGLT2I and DPP4I between January 1, 2015 and December 31, 2019 in Hong Kong. Exclusion criteria were <1-month exposure or exposure to both medication classes, or prior diagnosis of dementia or major neurological/psychiatric diseases. Primary outcomes were new-onset dementia, Alzheimer's, and Parkinson's. Secondary outcomes were all-cause, cardiovascular, and cerebrovascular mortality. Results: A total of 13,276 SGLT2I and 36,544 DPP4I users (total n = 51,460; median age: 66.3 years old [interquartile range (IQR): 58-76], 55.65% men) were studied (follow-up: 472 [120-792] days). After 1:2 matching (SGLT2I: n = 13,283; DPP4I: n = 26,545), SGLT2I users had lower incidences of dementia (0.19 vs. 0.78%, p < 0.0001), Alzheimer's (0.01 vs. 0.1%, p = 0.0047), Parkinson's disease (0.02 vs. 0.14%, p = 0.0006), all-cause (5.48 vs. 12.69%, p < 0.0001), cerebrovascular (0.88 vs. 3.88%, p < 0.0001), and cardiovascular mortality (0.49 vs. 3.75%, p < 0.0001). Cox regression showed that SGLT2I use was associated with lower risks of dementia (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: [0.27-0.61], P < 0.0001), Parkinson's (HR:0.28, 95% CI: [0.09-0.91], P = 0.0349), all-cause (HR:0.84, 95% CI: [0.77-0.91], P < 0.0001), cardiovascular (HR:0.64, 95% CI: [0.49-0.85], P = 0.0017), and cerebrovascular (HR:0.36, 95% CI: [0.3-0.43], P < 0.0001) mortality. Conclusions: The use of SGLT2I is associated with lower risks of dementia, Parkinson's disease, and cerebrovascular mortality compared with DPP4I use after 1:2 ratio propensity score matching.

Dataset Information

Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study.

Aims

Materials and methods

Results

Conclusion

Publications

Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study.

Similar Datasets

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