Effect of adding GLP-1RA on mortality, cardiovascular events, and metabolic outcomes among insulin-treated patients with type 2 diabetes: A large retrospective UK cohort study

Anyanwagu, Uchenna; Mamza, Jil; Donnelly, Richard; Idris, Iskandar

doi:10.1016/j.ahj.2017.10.003

Cited by 16 publications

(39 citation statements)

References 28 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%

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%

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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“…THIN database has been validated and shown it to be demographically representative of the UK population in terms of demography, disease prevalence and mortality [21]. We have published extensively in our research group, using the THIN database in evaluating diabetesrelated outcomes in routine clinical practice [22,23].…”

Section: Methodsmentioning

confidence: 99%

The relationship between urinary albumin excretion, cardiovascular outcomes and total mortality among a large cohort of insulin-treated patients with type 2 diabetes in routine primary care practices

Anyanwagu

Donnelly

Idris

2018

Nephrology Dialysis Transplantation

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Background Albuminuria is a recognized diagnostic and prognostic marker of chronic kidney disease and cardiovascular (CV) risk but the well-known relationship between increments in urinary albumin:creatinine ratio (UACR) and CV outcomes and mortality has not been fully explored in insulin-treated patients with type 2 diabetes (T2D) in routine clinical care. Methods We investigated data for insulin users with T2D from UK general practices between 2007 and 2014. The UACR at the time of insulin initiation was measured and categorized as <10, 10– 29, 30–300 and >300 mg/g. Patients were followed up for 5 years or the earliest occurrence of all-cause mortality, non-fatal myocardial infarction or stroke. Cox proportional hazards models were fitted to estimate the risk of a composite of these events. Results A total of 12 725 patients with T2D (mean age 58.6 ± 13.8 years, mean haemoglobin A1c 8.7 ± 1.8%) initiating insulin therapy between 2007 and 2014 met the inclusion criteria. Compared with patients whose ACR levels at insulin initiation were <10 mg/g, the adjusted risk of the 3-point composite endpoint was 9, 30 and 98% higher in those with ACR levels between 10–29, 30–300 and >300 mg/g, respectively, after a follow-up period of 5 years. The ACR category on its own did not predict risk of all-cause mortality. Conclusions This study shows that in patients with T2D on insulin therapy, increased urinary ACR is independently associated with an increased risk of major adverse CV events and all-cause mortality.

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“…While the mechanism for the reduction of mortality outcome remains unclear, concurrent use of a glucose-lowering therapy with insulin is used widely. In a previous study within this same population cohort, we showed that the use of GLP-1 with insulin was associated with reduced CV events and total mortality compared with insulin alone [23]. Thus, the identification of patients at a high risk of CV events based on ACR and eGFR status would not only trigger the application of an aggressive CV reduction strategy, but also a concurrent use of appropriate glucose-lowering therapies with favourable effects on weight, albuminuria, and CV outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…It has been validated and shown to be demographically representative of the UK population in terms of disease demography, prevalence, and mortality [21]. Like many others, our research group has extensively used it in evaluating diabetes-related outcomes in routine clinical practice [22, 23]. …”

Section: Methodsmentioning

confidence: 99%

Individual and Combined Relationship between Reduced eGFR and/or Increased Urinary Albumin Excretion Rate with Mortality Risk among Insulin-Treated Patients with Type 2 Diabetes in Routine Practice

Anyanwagu¹,

Donnelly²,

Idris³

2018

Kidney Dis

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Background: A low estimated glomerular filtration rate (eGFR) and an increased urinary albumin-to-creatinine ratio (ACR) are well-recognised prognostic markers of cardiovascular (CV) risk, but their individual and combined relationship with CV disease and total mortality among insulin-treated type 2 diabetes (T2D) patients in routine clinical care is unclear. Methods: We analysed data for insulin users with T2D from UK general practices between 2007 and 2014 and examined the association between mortality rates and chronic kidney disease [categorised by low eGFR (< 60 mL/min/1.73 m²), high eGFR (≥60 mL/min/1.73 m²), low ACR (< 300 mg/g); and high ACR (≥300 mg/g) at insulin initiation] after a 5-year follow-up period using Cox proportional hazard models. Results: A total of 18,227 patients were identified (mean age: 61.5 ± 13.8 years, mean HbA1c: 8.6 ± 1.8%). After adjusting for confounders, when compared to adults on insulin therapy with an eGFR < 60 and an ACR ≥300 (low eGFR + high ACR) after a follow-up period of 5 years, patients with an eGFR < 60 and an ACR < 300 (low eGFR + low ACR) had a 6% lower mortality rate (aHR: 0.94; 95% CI 0.79–1.12); those with an eGFR > 60 and an ACR ≥300 (high eGFR + high ACR) had a 20% lower mortality rate (aHR: 0.80; 95% CI 0.68–0.96); and those with an eGFR > 60 and an ACR < 300 (high eGFR + low ACR) had the lowest death rate (28% less; aHR: 0.72; 95% CI 0.59–0.87). Conclusion: This study shows that among a large cohort of insulin-treated T2D patients in routine practice, the combination of reduced eGFR with increased ACR was associated with the greatest risk of premature death, followed closely by those with reduced eGFR and normal ACR levels. Adoption of aggressive CV risk management strategies to reduce mortality in patients with a low eGFR and albuminuria is essential in high-risk patients with T2D.

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Effect of adding GLP-1RA on mortality, cardiovascular events, and metabolic outcomes among insulin-treated patients with type 2 diabetes: A large retrospective UK cohort study

Abstract: Based on a large UK cohort in routine clinical practice, adding a GLP-1RA to insulin therapy is associated with a reduction in risk of composite CV events and all-cause mortality but a nonsignificant higher risk of hospitalization for heart failure in overweight patients with T2D.

Cited by 16 publications

References 28 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

The relationship between urinary albumin excretion, cardiovascular outcomes and total mortality among a large cohort of insulin-treated patients with type 2 diabetes in routine primary care practices

Individual and Combined Relationship between Reduced eGFR and/or Increased Urinary Albumin Excretion Rate with Mortality Risk among Insulin-Treated Patients with Type 2 Diabetes in Routine Practice

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