Applying <scp>REWIND</scp> cardiovascular disease criteria to <scp>SUSTAIN</scp> 6 and <scp>PIONEER</scp> 6: An exploratory analysis of cardiovascular outcomes with semaglutide

Verma, Subodh; Fainberg, Udi; Husain, Mansoor; Rasmussen, Søren; Rydén, Lars; Ripa, Maria Sejersten; Buse, John B.

doi:10.1111/dom.14360

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…Our findings align with the literature evidence supporting the prominent place of semaglutide in treating T2D patients at high CV risk [12,26,37]. Indeed, data from various clinical trials highlighted the effectiveness of this treatment even compared with other GLP-1 agonists [14,15,38,39].…”

Section: Discussionsupporting

confidence: 91%

“…Semaglutide reduced MACE in people with T2D at a high risk of CV disease in the SUSTAIN 6 trial, resulting in improved CV risk factors and increased life-years of the patients who practiced this therapy as an add-on to their practiced hypoglycemic therapy; this was probably due to the underlying CV risk of these patients and the time of initiation of treatment with semaglutide [10,16,25,26]. This 4-month retrospective, real-world study of T2D patients showed that injectable semaglutide significantly reduced HbA1c levels and cIMT, supporting the effect of this treatment on subclinical atherosclerosis as previously shown for some but not all GLP-1RAs [27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

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Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes

Patti,

Giglio,

Allotta

et al. 2023

Biomedicines

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Background: Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist. Several trials reported the protective effect of injectable semaglutide on cardiovascular (CV) risk by reducing major adverse cardiovascular events in type 2 diabetes patients. Strong preclinical evidence supports the CV benefits of semaglutide through an effect on atherosclerosis. However, scant evidence is available about the protective mechanisms of semaglutide in clinical practice. Methods: A retrospective observational study was conducted among consecutive type 2 diabetes patients treated with injectable semaglutide in Italy between November 2019 and January 2021 when the drug was first available in the country. The primary aims were the assessment of the carotid intima-media thickness (cIMT) and hemoglobin A1c (HbA1c) levels. The secondary aims were the evaluation of anthropometric, glycemic, and hepatic parameters and plasma lipids, including the assessment of the triglyceride/high-density lipoprotein ratio as an indirect marker of atherogenic small, dense low-density lipoprotein particles. Results: Injectable semaglutide reduced HbA1c and cIMT. An improvement in CV risk factors and the triglyceride/high-density lipoprotein ratio was reported. Moreover, through correlation analyses, we found that hepatic fibrosis and steatosis indices and the anthropometric, hepatic, and glycemic parameters, as well as plasma lipids, were unrelated to the variations in cIMT and HbA1c. Conclusions: Our findings suggest the effect of injectable semaglutide on atherosclerosis as a key CV protective mechanism. Considering the favorable effects on atherogenic lipoproteins and hepatic steatosis indices, our results support the pleiotropic effect of semaglutide beyond glycemic control.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes

Patti,

Giglio,

Allotta

et al. 2023

Biomedicines

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“…However, the REWIND (dulaglutide) trial used different criteria for CVD than SUS-TAIN and PIONEER (semaglutide) [6]. Nevertheless, a pooled posthoc analysis of SUSTAIN-6 and PIONEER-6 trials using the REWIND CVD criteria suggested that semaglutide may also be extended to patients with type 2 diabetes across the CV risk continuum, consistent with dulaglutide results from REWIND [7]. Thus, GLP-1RA could be considered in people with type 2 diabetes with either previous CVD or cardiovascular risk factors.…”

Section: Introductionmentioning

confidence: 77%

Do Glucagonlike Peptide-1 Receptor Agonist and Sodium-glucose Co-transporter 2 Inhibitor Prescriptions in Germany Reflect Recommendations for Type 2 Diabetes with Cardiovascular Disease of the ADA/EASD Consensus Report?

Barth¹,

Kostev²,

Krensel

et al. 2022

Exp Clin Endocrinol Diabetes

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Objectives: To analyze whether prescription use of GLP-1RA and SGLT2i in individuals with type 2 diabetes with cardiovascular disease (CVD) has increased after the ADA/EASD consensus guidelines (2018) in a German Real-World setting, and which clinical characteristics are associated with prescription use of these drugs. Methods: The Disease Analyzer database (IQVIA) comprises a representative panel of 1,373 general practitioners, diabetologists and cardiologists throughout Germany (01/2015-12/2020: 12.6 million patients). Newly diagnosed type 2 diabetes (n=45,531) was identified by ICD-10 codes (E11). Matching (1:1) on practice specialty, sex, age at and year of diabetes diagnosis was performed for CVD. Logistic regression models were fitted to obtain adjusted odds ratios (OR) for characteristics associated with prescription use (median follow-up: 1.9 years). Results: Overall, 35% of patients (n=16,006) were treated with glucose-lowering drugs during the first year after type 2 diabetes diagnosis (HbA1c ≥7.0%: 80%). GLP-1RA (2.4%) and SGLT2i (8.5%) were rarely prescribed. After the consensus, use of both GLP-1RA and SGLT2i increased, however, almost independently of pre-existing CVD (12/2019-11/2020 vs. 12/2017-11/2018: yes, no): GLP-1RA: from 5.7% to 9.2%, 5.2% to 7.6%; SGLT2i: from 13.9% to 20.4%, 12.1% to 16.6%. Among cardiovascular risk factors, the largest OR for GLP-1RA was found for obesity (4.5; 95%CI: 3.2-6.3). There was a moderate relationship of CVD both with SGLT2i (1.45; 1.32-1.60) and GLP-1RA (1.35; 1.08-1.69) prescriptions. A weak association of SGLT2i with heart failure (1.18; 95%CI: 1.05-1.32) was found. Conclusion: National prescription use of GLP-1RA and SGLT2i did not come close to the recommendation in subjects with CVD issued by the 2018 ADA/EASD consensus.

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A Methodological Framework for Meta-analysis and Clinical Interpretation of Subgroup Data: The Case of Major Adverse Cardiovascular Events With GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes

Karagiannis,

Tsapas,

Bekiari

et al. 2024

Diabetes Care

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We present a methodological framework for conducting and interpreting subgroup meta-analyses. Methodological steps comprised evaluation of clinical heterogeneity regarding the definition of subpopulations, credibility assessment of subgroup meta-analysis, and translation of relative into absolute treatment effects. We used subgroup data from type 2 diabetes cardiovascular outcomes trials (CVOTs) with glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors for patients with established cardiovascular disease and those at high cardiovascular risk without manifest cardiovascular disease. First, we evaluated the variability in definitions of the subpopulations across CVOTs using major adverse cardiovascular events (MACE) incidence in the placebo arm as a proxy for baseline cardiovascular risk. As baseline risk did not differ considerably across CVOTs, we conducted subgroup meta-analyses of hazard ratios (HRs) for MACE and assessed the credibility of a potential effect modification. Results suggested using the same overall relative effect for each of the two subpopulations (HR 0.85, 95% CI 0.80–0.90, for GLP-1 receptor agonists and HR 0.91, 95% CI 0.85–0.97, for SGLT2 inhibitors). Finally, we calculated 5-year absolute treatment effects (number of fewer patients with event per 1,000 patients). Treatment with GLP-1 receptor agonists resulted in 30 fewer patients with event in the subpopulation with established cardiovascular disease and 14 fewer patients with event in patients without manifest cardiovascular disease. For SGLT2 inhibitors, the respective absolute effects were 18 and 8 fewer patients with event per 1,000 patients. This framework can be applied to subgroup meta-analyses regardless of outcomes or modification variables.

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Applying REWIND cardiovascular disease criteria to SUSTAIN 6 and PIONEER 6: An exploratory analysis of cardiovascular outcomes with semaglutide

Cited by 3 publications

References 7 publications

Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes

Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes

Do Glucagonlike Peptide-1 Receptor Agonist and Sodium-glucose Co-transporter 2 Inhibitor Prescriptions in Germany Reflect Recommendations for Type 2 Diabetes with Cardiovascular Disease of the ADA/EASD Consensus Report?

A Methodological Framework for Meta-analysis and Clinical Interpretation of Subgroup Data: The Case of Major Adverse Cardiovascular Events With GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes

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