Glucose-lowering drug use and new-onset atrial fibrillation in patients with diabetes mellitus

Fauchier, Grégoire; Bisson, Arnaud; Bodin, Alexandre; Herbert, Julien; Angoulvant, Denis; Ducluzeau, Pierre Henri; Lip, Gregory Y.H.; Fauchier, Laurent

doi:10.1007/s00125-021-05551-y

Cited by 18 publications

(10 citation statements)

References 8 publications

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“…Due to the important role in the initiation and maintenance of AF medicated by sympathetic overflow [ 55 ], this effect may raise the possibility of an increased risk of AF. Indeed, recent observational studies have shown that the use of GLP-1RA was independently associated with a higher risk of incident AF (HR 2.27; 95% CI 1.49–3.47) among participants with diabetes [ 29 ]. The post hoc analysis of the HARMONY trial also showed that albiglutide was associated with a greater risk of AF and tachyarrhythmia [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…To date, direct comparisons of SGLT2i, GLP-1RA, and DPP4i regarding the risk of AF among patients with type 2 diabetes are scarce. Although a few network metaanalyses were aimed to compare the risk of incident AF between SGLT2i, GLP-1RA, and other anti-hypoglycemic agents, the above studies show conflicting results [24][25][26][27][28][29]. Also, the data from randomized and placebocontrolled studies may be incomplete because they were derived from the documentation of adverse effects and were not predefined for systematically identifying AF.…”

Section: Limitationsmentioning

confidence: 99%

“…Also, whether these drugs are associated with a lower risk of AF remains unclear. Recent meta-analyses comparing the risk of incident atrial fibrillation (AF) between users of SGLT2i, GLP1-RA, and placebo (DPP4i and other anti-hypoglycemic agents) have shown conflicting results [24][25][26][27][28][29]. Some analyses have indicated that DPP4i treatment was associated with a higher risk for atrial arrhythmias [29,30].…”

Section: Introductionmentioning

confidence: 99%

“…Recent meta-analyses comparing the risk of incident atrial fibrillation (AF) between users of SGLT2i, GLP1-RA, and placebo (DPP4i and other anti-hypoglycemic agents) have shown conflicting results [24][25][26][27][28][29]. Some analyses have indicated that DPP4i treatment was associated with a higher risk for atrial arrhythmias [29,30]. To date, a direct comparison between SGLT2i, GLP-1RA, and DPP4i regarding the risk of incident AF has not been conducted.…”

Section: Introductionmentioning

confidence: 99%

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The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

Chan

Chao

Chen

et al. 2022

Cardiovasc Diabetol

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Background Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients. Methods In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. Results After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84–0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63–0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86–1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02). Conclusions Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

Chan

Chao

Chen

et al. 2022

Cardiovasc Diabetol

Self Cite

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show abstract

“…At present, there are inconsistencies in the conclusions of previous studies regarding the relationship between GLP-1RAs and arrhythmias. The result of a longitudinal cohort study showed that the use of GLP-1 analogs was an independent risk factor associated with a higher incidence of atrial fibrillation (AF) ( 7 ). A meta-analysis evaluating cardiovascular safety of albiglutide found that more patients had AF or atrial flutter (AFL) in the experimental arm than in the compared arm ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

A meta-analysis evaluating indirectly GLP-1 receptor agonists and arrhythmias in patients with type 2 diabetes and myocardial infarction

Liu

Bian

et al. 2022

Front. Cardiovasc. Med.

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AimsAt present, the effects of Glucagon-Like Peptide 1 Receptor agonists (GLP-1RAs) on arrhythmia in patients with type 2 diabetes mellitus (T2DM) and myocardial infarction (MI) are still unclear. Hence, this systematic review and meta-analysis aimed to investigate this association.Methods and resultsPubMed, Embase, Cochrane Library, and Web of Science were searched from inception to 30 April 2022. Randomized controlled trials (RCTs) that compared GLP-1RAs with placebo and met the critical criterion of a proportion of patients with T2DM and MI > 30% were included to verify our purpose indirectly. The outcomes of interest included atrial arrhythmias, ventricular arrhythmias, atrioventricular block (AVB), sinus arrhythmia, and cardiac arrest. Relative risk (RR) and 95% confidence intervals (CI) were pooled using a random-effects model. We included five RCTs with altogether 31,314 patients. In these trials, the highest proportion of patients with T2DM and MI was 82.6%, while the lowest was 30.7%. Compared to placebo, GLP-1RAs were associated with a lower risk of atrial arrhythmias (RR 0.81, 95% CI 0.70–0.95). There was no significant difference in the risk of ventricular arrhythmias (RR 1.26, 95% CI 0.87–1.80), AVB (RR 0.95, 95% CI 0.63–1.42), sinus arrhythmia (RR 0.62, 95% CI 0.26–1.49), and cardiac arrest (RR 0.97, 95% CI 0.52–1.83) between groups.ConclusionGLP-1RAs may be associated with reduced risk for atrial arrhythmias, which seems more significant for patients with T2DM combined with MI. More studies are needed to clarify the definitive anti-arrhythmic role of this drug.

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Association of Sodium-Glucose Cotransporter-2 Inhibitors With Incident Atrial Fibrillation in Older Adults With Type 2 Diabetes

et al. 2022

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ImportanceSodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated many cardiovascular and kidney function benefits for patients with type 2 diabetes (T2D). However, the results of SGLT-2i use in primary prevention of atrial fibrillation (AF) were inconsistent in clinical trials, and incident AF was not a prespecified end point.ObjectiveTo examine incident AF with initiation of an SGLT-2i compared with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a glucagonlike peptide-1 receptor agonist (GLP-1RA) among older adults (aged ≥66 years) with T2D in routine clinical practice.Design, Setting, and ParticipantsA population-based new-user cohort study included older adults with T2D who had no history of AF and were enrolled in Medicare fee-for-service from April 1, 2013, to December 31, 2018. Data analysis was performed from June 28 to December 1, 2021.ExposuresTo control for potential confounding, new users of SGLT-2i were 1:1 propensity score (PS)–matched to new users of DPP-4is or GLP-1RAs in 2 pairwise comparisons based on 138 baseline covariates.Main Outcomes and MeasuresThe primary outcome was incident AF, defined as an inpatient diagnosis code for AF. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years, with their 95% CIs, were estimated in the PS-matched groups.ResultsNew users of SGLT-2is were 1:1 PS-matched to new users of a DPP-4i (n = 74 868) or GLP-1RA (n = 80 475). Overall, the mean (SD) age of study participants was 72 (5) years, and 165 984 were women (53.4%). The risk of incident AF was lower in the SGLT-2i group than the matched DPP-4i group (HR, 0.82; 95% CI, 0.76 to 0.89; RD, –3.7; 95% CI, –5.2 to –2.2 per 1000 person-years) or the matched GLP-1RA group (HR, 0.90; 95% CI, 0.83 to 0.98; RD, –1.8; 95% CI, –3.2 to –0.3 per 1000 person-years). Results were consistent across several sensitivity and subgroup analyses.Conclusions and RelevanceThe findings of this study suggest that the initiation of an SGLT-2i was associated with a reduced risk of incident AF compared with a DPP-4i or GLP-1RA. The results may be helpful when weighing the potential risks and benefits of various glucose level–lowering agents in older adults with T2D.

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Glucose-lowering drug use and new-onset atrial fibrillation in patients with diabetes mellitus

Cited by 18 publications

References 8 publications

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

A meta-analysis evaluating indirectly GLP-1 receptor agonists and arrhythmias in patients with type 2 diabetes and myocardial infarction

Association of Sodium-Glucose Cotransporter-2 Inhibitors With Incident Atrial Fibrillation in Older Adults With Type 2 Diabetes

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