SGLT-2 Inhibitors and GLP-1 Agonists: First-Line Therapy for Diabetes With Established Cardiovascular Disease

2019 ◽  
Vol 24 (5) ◽  
pp. 422-427 ◽  
Author(s):  
Aparna P. Sajja ◽  
Amit K. Dey ◽  
Avirup Guha ◽  
Youssef Elnabawi ◽  
Aditya A. Joshi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Growing Body ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Sodium Glucose Cotransport

There is a growing body of evidence that diabetes represents a significant and largely modifiable risk factor for cardiovascular disease (CVD). It is known to markedly increase the risk of CVD—with CVD accounting for 2 of every 3 deaths in patients with diabetes. It is suggested that once patients with diabetes develop clinical coronary disease, they have a grim prognosis. In 2008, the Food and Drug Association mandated the evidence of CV safety in any new diabetic therapy, leading to a multitude of large CV outcome trials to assess CV risk from these medications. However, several of these outcome trials with novel antidiabetic therapies have demonstrated not only safety but a clear and definite CV advantage in patients with type 2 diabetes. In this review, we discuss 2 relatively newer classes of diabetic drugs, sodium glucose cotransport 2 inhibitors and glucagon-like peptide 1 agonists, evaluate their efficacy in improving CV outcomes, and discuss the future of CV prevention with these agents.

Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases

2019 ◽  
Vol 26 (2_suppl) ◽  
pp. 73-80 ◽  
Author(s):  
Francesco Prattichizzo ◽  
Lucia La Sala ◽  
Lars Rydén ◽  
Nikolaus Marx ◽  
Marc Ferrini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Receptor Agonist ◽  
Glucose Lowering ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes mellitus is a major risk factor for developing cardiovascular disease, and many patients with diabetes have prevalent cardiovascular complications. Recent cardiovascular outcome clinical trials suggest that certain new glucose-lowering drugs are accompanied by additional cardioprotective properties. Indeed, selected glucagon-like peptide-1 receptor agonists have a proved cardiovascular benefit in terms of a reduced incidence of ischaemic events, while sodium/glucose co-transporter-2 inhibitors have also shown significant protection, with a striking effect on heart failure and renal endpoints. These findings have been integrated in recent guidelines which now recommend prescribing (when initial metformin monotherapy fails) a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor with clinical trial-confirmed benefit in patients with diabetes and atherosclerotic cardiovascular disease, and a sodium/glucose co-transporter-2 inhibitor in such patients with heart failure or chronic kidney disease at initial stages. Furthermore, the new 2019 European Society of Cardiology guidelines in collaboration with the European Association for the Study of Diabetes recommend a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor in treatment-naive patients with type 2 diabetes mellitus with pre-existing cardiovascular disease or at high cardiovascular risk. Future research will disentangle the mechanisms underpinning these beneficial effects and will also establish to what extent these results are generalisable to the whole diabetes population. In the meantime, available evidence should prompt a wide diffusion of these two classes of drugs among patients with diabetes and cardiovascular disease. Here, we briefly summarise recent findings emerging from cardiovascular outcome clinical trials, discuss their impact on treatment algorithms and propose new possible approaches to improve our knowledge further regarding the cardiovascular effect of glucose-lowering medications.

Insulin as a First-Line Therapy in Type 2 Diabetes: Should the use of sulfonylureas be halted?

Diabetes Care ◽  
2008 ◽  
Vol 31 (Supplement 2) ◽  
pp. S136-S139 ◽  
Author(s):  
E. Standl ◽  
O. Schnell
Keyword(s):  
Type 2 Diabetes ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract 15526: Glucagon-like Peptide-1 Receptor Agonists Reduce Adverse Cardiovascular Disease (CVD) Events in Patients With Type 2 Diabetes: An Assessment of Heterogeneity Among CVD Outcomes and a Meta-regression Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Simran Grewal ◽  
Ninad Zaman ◽  
Louis Borgatta ◽  
Matthew Nudy ◽  
Brandon Peterson
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Death ◽  
Nonfatal Stroke ◽  
Significant Heterogeneity ◽  
Receptor Agonists ◽  
Meta Regression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Introduction: Recent evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce adverse cardiovascular disease (CVD) events. The objective of this study is to analyze randomized controlled trials (RCTs) testing GLP-1 RA’s effects on CVD among participants with type 2 diabetes (T2DM). Methods: RCTs comparing GLP-1 RA versus placebo among participants with T2DM were identified using PubMed and Cochrane databases. The endpoints of this analysis included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi 2 and I 2 tests. For any endpoint with significant heterogeneity, a meta-regression was performed using baseline hemoglobin A1C (A1C) in each RCT as the moderator and a R 2 value was calculated. Results: 7 RCTs (N = 56,004) were identified with 174,163 patient years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83-0.95], cardiovascular death [RR 0.88, 95% CI 0.81-0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77-0.94]. There was no significant heterogeneity among these RCTs (Figure 1). GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.82-1.02]. However, there was significant heterogeneity among these RCTS (Chi 2 =12.94, p=0.04, I 2 =54%). When accounting for A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p=0.23, I 2 =27%). A relationship between A1C and GLP-1 RA’s effect on nonfatal MI (R 2 =0.64, Figure 1) was observed when performing the meta-regression. Conclusion: GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke in patients with T2DM with minimal heterogeneity among RCTs. GLP-1 RA did not reduce nonfatal MI, however there may be an association between A1C and GLP-1 RA’s effect on nonfatal MI.

scholarly journals Glucagon-Like Peptide 1 Receptor Agonists and Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (12) ◽  
pp. 1205-1218 ◽  
Author(s):  
Muhammad Shahzeb Khan ◽  
Gregg C. Fonarow ◽  
Darren K. McGuire ◽  
Adrian F. Hernandez ◽  
Muthiah Vaduganathan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Ejection Fraction ◽  
Atherosclerotic Cardiovascular Disease ◽  
Reduced Ejection Fraction ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease– and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.

Rationale and design of a clinical trial to evaluate metformin and colesevelam HCl as first-line therapy in type 2 diabetes and colesevelam HCl in prediabetes

2009 ◽  
Vol 25 (9) ◽  
pp. 2239-2249 ◽  
Author(s):  
Michael R. Jones ◽  
Sunder Mudaliar ◽  
Eric Hernandez-Triana ◽  
Ambika G. Unnikrishnan ◽  
Yu-Ling Lai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Update on RAAS Modulation for the Treatment of Diabetic Cardiovascular Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Stella Bernardi ◽  
Andrea Michelli ◽  
Giulia Zuolo ◽  
Riccardo Candido ◽  
Bruno Fabris
Keyword(s):  
Cardiovascular Disease ◽  
Diabetic Patients ◽  
Paradigm Shifts ◽  
Angiotensin Ii Receptor ◽  
First Line ◽  
Chronic Complications ◽  
First Line Therapy ◽  
Patients With Diabetes ◽  
Receptor Blockers ◽  
Diabetic Population

Since the advent of insulin, the improvements in diabetes detection and the therapies to treat hyperglycemia have reduced the mortality of acute metabolic emergencies, such that today chronic complications are the major cause of morbidity and mortality among diabetic patients. More than half of the mortality that is seen in the diabetic population can be ascribed to cardiovascular disease (CVD), which includes not only myocardial infarction due to premature atherosclerosis but also diabetic cardiomyopathy. The importance of renin-angiotensin-aldosterone system (RAAS) antagonism in the prevention of diabetic CVD has demonstrated the key role that the RAAS plays in diabetic CVD onset and development. Today, ACE inhibitors and angiotensin II receptor blockers represent the first line therapy for primary and secondary CVD prevention in patients with diabetes. Recent research has uncovered new dimensions of the RAAS and, therefore, new potential therapeutic targets against diabetic CVD. Here we describe the timeline of paradigm shifts in RAAS understanding, how diabetes modifies the RAAS, and what new parts of the RAAS pathway could be targeted in order to achieve RAAS modulation against diabetic CVD.

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