Cardiovascular outcomes after initiating GLP-1 receptor agonist or basal insulin for the routine treatment of type 2 diabetes: a region-wide retrospective study

Abstract Aim We aimed to compare cardiovascular outcomes of patients with type 2 diabetes (T2D) who initiated GLP-1 receptor agonists (GLP-1RA) or basal insulin (BI) under routine care. Methods We accessed the administrative claims database of the Veneto Region (Italy) to identify new users of GLP-1RA or BI in 2014–2018. Propensity score matching (PSM) was implemented to obtain two cohorts of patients with superimposable characteristics. The primary endpoint was the 3-point major adverse cardiovascular events (3P-MACE). Secondary endpoints included 3P-MACE components, hospitalization for heart failure, revascularizations, and adverse events. Results From a background population of 5,242,201 citizens, 330,193 were identified as having diabetes. PSM produced two very well matched cohorts of 4063 patients each, who initiated GLP-1RA or BI after an average of 2.5 other diabetes drug classes. Patients were 63-year-old and only 15% had a baseline history of cardiovascular disease. During a median follow-up of 24 months in the intention-to-treat analysis, 3P-MACE occurred less frequently in the GLP-1RA cohort (HR versus BI 0.59; 95% CI 0.50–0.71; p < 0.001). All secondary cardiovascular endpoints were also significantly in favor of GLP-1RA. Results were confirmed in the as-treated approach and in several stratified analyses. According to the E-value, confounding by unmeasured variables were unlikely to entirely explain between-group differences in cardiovascular outcomes. Conclusions Patients with T2D who initiated a GLP-1RA experienced far better cardiovascular outcomes than did matched patients who initiated a BI in the same healthcare system. These finding supports prioritization of GLP-1RA as the first injectable regimen for the management of T2D.

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Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A PostHoc Analysis from the CREDENCE Trial

Journal of the American Society of Nephrology ◽

10.1681/asn.2020050723 ◽

2020 ◽

Vol 31 (12) ◽

pp. 2925-2936 ◽

Cited By ~ 1

Author(s):

Megumi Oshima ◽

Brendon L. Neuen ◽

JingWei Li ◽

Vlado Perkovic ◽

David M. Charytan ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Cardiovascular Events ◽

Renin Angiotensin System ◽

Cardiovascular Death ◽

Cardiovascular Outcomes ◽

Major Adverse Cardiovascular Events ◽

Early Change ◽

Sodium Glucose Cotransporter

BackgroundThe association between early changes in albuminuria and kidney and cardiovascular events is primarily based on trials of renin-angiotensin system blockade. It is unclear whether this association occurs with sodium-glucose cotransporter 2 inhibition.MethodsThe Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial enrolled 4401 patients with type 2 diabetes and CKD (urinary albumin-creatinine ratio [UACR] >300 mg/g). This post hoc analysis assessed canagliflozin’s effect on albuminuria and how early change in albuminuria (baseline to week 26) is associated with the primary kidney outcome (ESKD, doubling of serum creatinine, or kidney death), major adverse cardiovascular events, and hospitalization for heart failure or cardiovascular death.ResultsComplete data for early change in albuminuria and other covariates were available for 3836 (87.2%) participants in the CREDENCE trial. Compared with placebo, canagliflozin lowered UACR by 31% (95% confidence interval [95% CI], 27% to 36%) at week 26, and significantly increased the likelihood of achieving a 30% reduction in UACR (odds ratio, 2.69; 95% CI, 2.35 to 3.07). Each 30% decrease in UACR over the first 26 weeks was independently associated with a lower hazard for the primary kidney outcome (hazard ratio [HR], 0.71; 95% CI, 0.67 to 0.76; P<0.001), major adverse cardiovascular events (HR, 0.92; 95% CI, 0.88 to 0.96; P<0.001), and hospitalization for heart failure or cardiovascular death (HR, 0.86; 95% CI, 0.81 to 0.90; P<0.001). Residual albuminuria levels at week 26 remained a strong independent risk factor for kidney and cardiovascular events, overall and in each treatment arm.ConclusionsIn people with type 2 diabetes and CKD, use of canagliflozin results in early, sustained reductions in albuminuria, which were independently associated with long-term kidney and cardiovascular outcomes.

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MANAGEMENT OF ENDOCRINE DISEASE: Are all GLP-1 agonists equal in the treatment of type 2 diabetes?

Acta Endocrinologica ◽

10.1530/eje-19-0566 ◽

2019 ◽

Vol 181 (6) ◽

pp. R211-R234 ◽

Cited By ~ 25

Author(s):

Michael A Nauck ◽

Juris J Meier

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Receptor Agonist ◽

Parent Compound ◽

Cardiovascular Outcomes ◽

Major Adverse Cardiovascular Events ◽

Oral Glucose ◽

Duration Of Action ◽

Glucose Lowering

GLP-1, a peptide hormone secreted from the gut, stimulating insulin and suppressing glucagon secretion was identified as a parent compound for novel treatments of diabetes, but was degraded (dipeptidyl peptidase-4) and eliminated (mainly by kidneys) too fast (half-life 1–2 min) to be useful as a therapeutic agent. GLP-1 receptor agonist has been used to treat patients with type 2 diabetes since 2007, when exenatide (twice daily) was approved in 2007. Compounds with longer duration of action (once daily, once weekly) and with increasingly better efficacy with respect to glycaemic control and body weight reduction have been developed, and in a recent ADA/EASD consensus statement, were recommended as the first injectable diabetes therapy after failure of oral glucose-lowering medications. Most GLP-1 receptor agonists (lixisenatide q.d., liraglutide q.d., exenatide q.w., dulaglutide q.w., albiglutide q.w., semaglutide q.w., all for s.c. injection, and the first oral preparation, oral semaglutide) have been examined in cardiovascular outcomes studies. Beyond proving their safety in vulnerable patients, most of whom had pre-existing heart disease, liraglutide, semaglutide, albiglutide, and dulaglutide reduced the time to first major adverse cardiovascular events (non-fatal myocardial infarction and stroke, cardiovascular death). Liraglutide, in addition, reduced cardiovascular and all-cause mortality. It is the purpose of the present review to describe clinically important differences, regarding pharmacokinetic behaviour, glucose-lowering potency, effectiveness of reducing body weight and controlling other cardiovascular risk factors, and of the influence of GLP-1 receptor agonist treatment on cardiovascular outcomes in patients either presenting with or without pre-existing cardiovascular disease (atherosclerotic, ischemic or congestive heart failure).

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Tolerability and Effectiveness of Exenatide Once Weekly Relative to Basal Insulin Among Type 2 Diabetes Patients of Different Races in Routine Care

Diabetes Therapy ◽

10.1007/s13300-017-0314-z ◽

2017 ◽

Vol 8 (6) ◽

pp. 1349-1364 ◽

Cited By ~ 2

Author(s):

Anthony P. Nunes ◽

Anita M. Loughlin ◽

Qing Qiao ◽

Stephen M. Ezzy ◽

Laura Yochum ◽

...

Keyword(s):

Type 2 Diabetes ◽

Basal Insulin ◽

Routine Care ◽

Diabetes Patients

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Impact of delaying treatment intensification with a glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes uncontrolled on basal insulin: A longitudinal study of a US administrative claims database

Diabetes Obesity and Metabolism ◽

10.1111/dom.13156 ◽

2017 ◽

Vol 20 (4) ◽

pp. 831-839 ◽

Cited By ~ 7

Author(s):

Liyue Tong ◽

Chunshen Pan ◽

Hongwei Wang ◽

Monica Bertolini ◽

Elisheva Lew ◽

...

Keyword(s):

Type 2 Diabetes ◽

Longitudinal Study ◽

Basal Insulin ◽

Receptor Agonist ◽

Administrative Claims ◽

Treatment Intensification ◽

Claims Database ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Cardiovascular Outcomes and HbA1c Among Patients With Type 2 Diabetes Newly Initiating GLP1RAs vs Basal Insulin

Case Medical Research ◽

10.31525/ct1-nct04034524 ◽

2019 ◽

Author(s):

Keyword(s):

Type 2 Diabetes ◽

Basal Insulin ◽

Cardiovascular Outcomes

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Cardiovascular outcomes and healthcare costs of liraglutide versus basal insulin for type 2 diabetes patients at high cardiovascular risk

Scientific Reports ◽

10.1038/s41598-020-80753-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wan-Chun Huang ◽

Yen-Chou Chen ◽

Chung-Hsuen Wu ◽

Yu Ko

Keyword(s):

Type 2 Diabetes ◽

Basal Insulin ◽

Healthcare Costs ◽

Medical Costs ◽

Cardiovascular Death ◽

Cardiovascular Outcomes ◽

Nonfatal Stroke ◽

Cvd Risk ◽

All Cause Mortality

AbstractWe aimed to compare the (1) clinical outcomes including composite cardiovascular outcomes, cardiovascular death, and all-cause death, and (2) healthcare costs of using liraglutide and basal insulin as an initial treatment for patients with type 2 diabetes mellitus (T2DM) and high cardiovascular diseases (CVD) risk. This is a retrospective cohort study using Taiwan’s Health and Welfare Database. A total of 1057 patients treated with liraglutide were identified and matched with 4600 patients treated with basal insulin. The liraglutide group had a lower risk of a composite CVD outcome (hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.50–0.85; p < 0.01), all-cause mortality (HR 0.40; 95% CI 0.28–0.59; p < 0.0001), and nonfatal stroke (HR 0.54; 95% CI 0.34–0.87; p = 0.01). Compared to the basal insulin group, the liraglutide group had lower median per-patient-per-month (PPPM) inpatient, emergency room (ER), and total medical costs, but higher median PPPM outpatient, total pharmacy, and total costs (all p < 0.0001). In conclusion, compared to basal insulin, liraglutide was found to be associated with reduced risk of a composite CVD outcome, nonfatal stroke, and all-cause mortality among high CVD risk patients with T2DM. In addition, liraglutide users had lower inpatient, ER, and total medical costs, but they had higher outpatient and total pharmacy costs.

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