Association of glucagon‐like peptide‐1 receptor agonist use and rates of acute myocardial infarction, stroke and overall mortality in patients with type 2 diabetes mellitus in a large integrated health system

Zimmerman, Robert S.; Hobbs, Todd; Wells, Brian J.; Kong, Sheldon X.; Kattan, Michael W.; Bouchard, Jonathan; Chagin, Kevin; Yu, Changhong; Sakurada, Brian; Milinovich, Alex; Weng, Wayne; Bauman, Janine; Pantalone, Kevin M.

doi:10.1111/dom.12969

Cited by 26 publications

(42 citation statements)

References 16 publications

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“…We identified sixteen observational cohort studies assessing CV outcomes, HHF and or all‐cause mortality in T2MD patients treated with GLP‐1 RAs: Best et al, 27 Mogensen et al, 28 Paul et al, 29 Vélez et al, 30 Patorno et al, 31 Kannan et al, 32 Ekström et al, 33 Anyanwagu et al, 34 Suissa et al, 35 Zimmerman et al, 36 Toulis et al, 37 Anyanwagu et al, 38 Patorno et al, 39 Dawwas et al, 40 Svanström et al 41 and O'Brien et al 42 The total number of patients exposed to GLP‐1 RAs was 285,436; ranging from 219 33 to 160,803 40 . (Table 2) Study periods span from 2005 27 to 2015 37 (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…All studies were conducted in Western databases validated for investigational purposes for the condition and outcomes of interest: most in US 27,29–32,36,39,40,42,43 and UK 33,35,37,38 ; Denmark, 28 Sweden, 34 and Sweden and Denmark 41 . European databases are electronic medical records (EMRs), with partial (in the UK, the Health Improvement Network [THIN] and the Clinical Practice Research Datalink [GPRD]) or universal general population coverage (Denmark and Sweden); in Danish databases 28,41 information about clinical variables is lacking.…”

Section: Resultsmentioning

confidence: 99%

“…European databases are electronic medical records (EMRs), with partial (in the UK, the Health Improvement Network [THIN] and the Clinical Practice Research Datalink [GPRD]) or universal general population coverage (Denmark and Sweden); in Danish databases 28,41 information about clinical variables is lacking. US studies were conducted in claims EHDs 27,29–32,37,39,40,42 and EMRs 32,36 …”

Section: Resultsmentioning

confidence: 99%

“…In two studies assessing the effect of canagliflozin 39 and DPP4 i 40 on HF, GLP‐1 RAs were the reference drugs. Three studies reported the percentage of use, 36–38 being exenatide and liraglutide the most used GLP‐1 RAs; two studies 37,38 made subgroup analysis for each agent. Two studies reported the use of dulaglutide—approved in September 2014—and albiglutide 39,40 no study included semaglutide (marketed in December 2017).…”

Section: Resultsmentioning

confidence: 99%

“…In five studies, comparators were other non‐insulin antidiabetic agents 27,29,30,36–38 . Eight studies compared GLP‐1 RAs vs a well‐defined class: vs SUs, 35 vs DPP‐4 i 40,41 (two with prior use of MET at baseline) or evaluated GLP‐1 RAs vs other second‐line therapies, all added to metformin: metformin with SUs as a reference 28,31–33 or DPP‐4 i, 31,42 thiazolidinediones or insulin 31 .…”

Section: Resultsmentioning

confidence: 99%

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Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs): A systematic review and meta‐analysis of observational cohort studies

Comoglio

Vidal

2020

Int J Clin Pract

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Background Cardiovascular outcomes trials (CVOTs) have assessed the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on major adverse cardiovascular events (MACE) and mortality in high cardiovascular (CV) risk populations. Observational research can provide complementary evidence about these effects in unselected populations. Aim To systematically review retrospective observational cohort studies conducted in electronic healthcare databases (EHDs) assessing GLP‐1 RAs´ effects on MACE and/or hospitalisation for heart failure (HHF) and/or all‐cause mortality in Type 2 diabetes mellitus (T2DM) patients. Methods We systematically searched studies meeting inclusion criteria, compared design, methods and population characteristics, assessed risk for bias and did a meta‐analysis (MA) using a random‐effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). Results Sixteen studies included 285,436 T2DM patients exposed to GLP‐1 RAs (exenatide bid, liraglutide, lixisenatide, long‐acting exenatide), n ranged from 219 to 160,803 patients. Comparators included: no exposure, other antidiabetic medications (OADs), combined OADs, canagliflozin or multiple comparators. Ten studies estimated all‐cause mortality, hazard ratios (HRs) ranged from 0.17 (95% CI 0.02‐1.22) to 1.29 (95% CI 0.54‐3.13). Thirteen studies assessed cardiovascular events and/or MACE; HRs ranged from 0.27 (95% CI 0.14‐0.53) to 1.11 (95% CI 0.99‐1.24). Eight studies assessed HHF, HRs ranged from 0.12 (95% CI 0.02‐0.66) to 1.64 (95% CI 1.28‐2.13). Excluding two studies because of temporal bias, we obtained pooled estimates for all‐cause mortality: HR 0.63 (0.44‐0.89), CV outcomes HR 0.84 (0.75‐0.94) and HHF; HR 0.94 (0.78‐1.14), (high between‐study variability: I2 = 83.35%; I2 = 70.3%; and I2 = 90.1%, respectively). Conclusion Pooled results of EHDs’ studies assessing GLP‐1 RAs effects favoured GLP‐1 RAs for all‐cause mortality and MACE while were neutral for HHF. Results should be interpreted cautiously because of studies’ substantial heterogeneity and limitations of observational research.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs): A systematic review and meta‐analysis of observational cohort studies

Comoglio

Vidal

2020

Int J Clin Pract

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Association of Second-line Antidiabetic Medications With Cardiovascular Events Among Insured Adults With Type 2 Diabetes

et al. 2018

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IMPORTANCE Understanding cardiovascular outcomes of initiating second-line antidiabetic medications (ADMs) may help inform treatment decisions after metformin alone is not sufficient or not tolerated. To date, no studies have compared the cardiovascular effects of all major second-line ADMs during this early decision point in the pharmacologic management of type 2 diabetes. OBJECTIVE To examine the association of second-line ADM classes with major adverse cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study among 132 737 insured adults with type 2 diabetes who started therapy with a second-line ADM after taking either metformin alone or no prior ADM. This study used 2011-2015 US nationwide administrative claims data. Data analysis was performed from January 2017 to October 2018. EXPOSURES Dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, thiazolidinediones (TZDs), basal insulin, and sulfonylureas or meglitinides (both referred to as sulfonylureas hereafter). The DPP-4 inhibitors served as the comparison group in all analyses. MAIN OUTCOMES AND MEASURES The primary outcome was time to first cardiovascular event after starting the second-line ADM. This composite outcome was based on hospitalization for the following cardiovascular conditions: congestive heart failure, stroke, ischemic heart disease, or peripheral artery disease. RESULTS Among 132 737 insured adult patients with type 2 diabetes (men, 55%; aged 45-64 years, 58%; white, 63%), there were 3480 incident cardiovascular events during 169 384 person-years of follow-up. Patients were censored after the first cardiovascular event, discontinuation of insurance coverage, transition from International Classification of Diseases, Ninth Revision (ICD-9) to end of ICD-9 coding, or 2 years of follow-up. After adjusting for patient, prescriber, and health plan characteristics, the risk of composite cardiovascular events after starting GLP-1 receptor agonists was lower than DPP-4 inhibitors (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96), but this finding was not significant in all sensitivity analyses. Cardiovascular event rates after starting treatment with SGLT-2 inhibitors (HR, 0.81; 95% CI, 0.57-1.53) and TZDs (HR, 0.92; 95% CI, 0.76-1.11) were not statistically different from DPP-4 inhibitors. The comparative risk of cardiovascular events was higher after starting treatment with sulfonylureas (HR, 1.36; 95% CI, 1.23-1.49) or basal insulin (HR, 2.03; 95% CI, 1.81-2.27) than DPP-4 inhibitors.

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Comparative cardiovascular effects of GLP‐1 agonists using real‐world data

Wallia

O’Brien

Hakimian

et al. 2023

Endocrino Diabet & Metabol

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Aims There is limited research using real‐world data to evaluate protective cardiovascular effects of glucagon‐like peptide‐1 (GLP‐1) agonists among adults with type 2 diabetes (T2D) early in treatment. Materials and Methods We conducted a retrospective, active comparator cohort study using 2011–2015 administrative claims data to compare cardiovascular disease (CVD) event rates following initiation of exenatide extended‐release (E‐ER), exenatide immediate‐release (E‐IR) or liraglutide in T2D adults who previously received no other antidiabetic medication (ADM) except metformin. The primary outcome was time to first major adverse CVD event (ischaemic heart disease, stroke, congestive heart failure or peripheral arterial disease) after starting GLP‐1. Cox proportional hazards regression was used to model the association between index GLP‐1 and CVD events, adjusting for baseline patient, prescriber and plan characteristics. Primary analyses included all patients with ≥2 prescription fills for the index GLP‐1, regardless of subsequent refill adherence or initiation of other ADM after index date. Results Compared with liraglutide, neither E‐ER nor E‐IR was associated with risk of composite major CVD events (hazard ratios [HRs] for E‐ER and E‐IR: 1.33 [95% C.I. 0.73–2.39] and 1.30 [0.81–2.09]). No associations were observed between event rates for individual CVD components. The HR for an ischaemic event with E‐IR relative to liraglutide was 1.85 (95% C.I. 0.97–3.53). Adjusting for time‐varying exposure to other ADM and CVD medications after index date produced similar results. Conclusions Initiating either immediate or extended‐release exenatide rather than liraglutide was not associated with significant differences in CVD risk in this observational real‐world study.

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Association of glucagon‐like peptide‐1 receptor agonist use and rates of acute myocardial infarction, stroke and overall mortality in patients with type 2 diabetes mellitus in a large integrated health system

Abstract: GLP-1RA exposure was found to be associated with a reduction in the risk of cardiovascular events observed and overall mortality among patients with T2D with and without established CVD, after adjusting for potential confounders.

Cited by 26 publications

References 16 publications

Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs): A systematic review and meta‐analysis of observational cohort studies

Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs): A systematic review and meta‐analysis of observational cohort studies

Association of Second-line Antidiabetic Medications With Cardiovascular Events Among Insured Adults With Type 2 Diabetes

Comparative cardiovascular effects of GLP‐1 agonists using real‐world data

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