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Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis.

ABSTRACT: Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline. Of 605 potentially relevant studies, 7 eligible RCTs comprising 2,082 patients were included.SGLT2i/DPP4i showed a greater reduction in HbA1c (weighted mean difference -0.6%, 95% CI -0.7 to -0.5%), fasting plasma glucose, 2?h postprandial plasma glucose, and body weight compared to PCB/DPP4i. The risk of hypoglycemia increased in SGLT2i/DPP4i compared to that in PCB/DPP4i only when insulin or sulfonylureas were included as a background therapy. The risk of urinary tract infection was not increased in SGLT2i/DPP4i; however, the risk of genital infection increased upon adding SGLT2 inhibitors to pre-existing DPP4 inhibitors. In conclusion, compared to PCB/DPP4i, SGLT2i/DPP4i achieved better glycemic control and greater weight reduction without increasing the risk of hypoglycemia and urinary tract infection in patients with inadequately controlled T2DM.

SUBMITTER: Min SH

PROVIDER: S-EPMC5849757 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis.

Min Se Hee SH Yoon Jeong-Hwa JH Moon Sun Joon SJ Hahn Seokyung S Cho Young Min YM

Scientific reports 20180313 1

Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin ...[more]

PMID: 29535389

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Project description:BackgroundWhether sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a lower risk of cardiovascular as well as adverse lower limb events in patients with type-2 diabetes mellitus (T2DM) and concomitant peripheral artery disease (PAD) is unclear. We aimed to evaluate the risk of cardiovascular and limb events, and death associated with the use of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal and national cohort of patients with T2DM.MethodsIn this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, we identified a total of 11,431 and 93,972 consecutive T2DM patients with PAD taking SGLT2i and DPP4i, respectively, from May 1, 2016, to December 31, 2017. We used 1:1 propensity score matching (PSM) to balance covariates across study groups. Patients were followed from the drug index date until the occurrence of clinical outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first.ResultsOverall, 56% and 44% of the patients were treated with dapagliflozin and empagliflozin, respectively. The use of SGLT2i had comparable risks of ischemic stroke and acute myocardial infarction, and was associated with lower risks of congestive heart failure (CHF) [hazard ratio (HR): 0.66; 95% confidence interval (CI) 0.49-0.89; p?=?0.0062], lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54-0.98; p?=?0.0367) or amputation (HR: 0.43; 95% CI 0.30-0.62; p?<?0.0001), and cardiovascular death (HR: 0.67; 95% CI 0.49-0.90; p?=?0.0089) when compared with the DDP4i group after PSM. The subgroup analysis revealed consistent results for CHF and major adverse limb outcomes for SGLT2i versus DPP4i among patients aged ? 75 years, the presence of chronic kidney disease and established cardiovascular disease was consistent with the main analysis.ConclusionsSGLT2i were associated with lower risks of CHF and adverse lower limb events compared with DPP4i among patients with T2DM and PAD in real-world practice.

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:Importance:The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown. Objective:To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis. Data Sources:MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017. Study Selection:Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment. Data Extraction and Synthesis:Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed. Main Outcomes and Measures:The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia. Results:This network meta-analysis of 236 trials randomizing 176?310 participants found SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups. SGLT-2 inhibitors (absolute RD, -0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than were the control groups. GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]). Conclusions and Relevance:In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

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.

Dataset Information

Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis.

Publications

Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis.

Similar Datasets

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