The effect of SGLT2 inhibitors, GLP1 agonists, and their sequential combination on cardiometabolic parameters: A randomized, prospective, intervention study

Bechlioulis, Aris; Chionidi, Ifigeneia; Liberopoulos, Evangelos; Naka, Katerina K.; Ntzani, Evangelia; Liatis, Stavros; Rizzo, Manfredi; Rizos, Evangelos C.

doi:10.1016/j.jdiacomp.2023.108436

Cited by 15 publications

(12 citation statements)

References 43 publications

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“…It was observed that systemic vascular resistance and lipoprotein(a) levels improved to a greater extent with liraglutide than empagliflozin, along with improvement in BMI, body and visceral fat, blood pressure, and HbA1c. However, no improvement in arterial stiffness indices was observed with empagliflozin or liraglutide or their combination in this study [ 115 ].…”

Section: Emerging Pharmacotherapiesmentioning

confidence: 77%

Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies

et al. 2023

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Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, in addition to apparent coronary heart disease, ischemia, and hypertension-related complications, has created a more challenging situation. Diabetes, as a predominant cardio-renal metabolic syndrome, is related to severe vascular risk factors, and it underlies various complex pathophysiological pathways at the metabolic and molecular level that progress and converge toward the development of diabetic cardiomyopathy (DCM). DCM involves several downstream cascades that cause structural and functional alterations of the diabetic heart, such as diastolic dysfunction progressing into systolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, and subsequent heart failure over time. The effects of glucagon-like peptide-1 (GLP-1) analogues and sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular (CV) outcomes in diabetes have shown promising results, including improved contractile bioenergetics and significant cardiovascular benefits. The purpose of this article is to highlight the various pathophysiological, metabolic, and molecular pathways that contribute to the development of DCM and its significant effects on cardiac morphology and functioning. Additionally, this article will discuss the potential therapies that may be available in the future.

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Section: Emerging Pharmacotherapiesmentioning

confidence: 77%

Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies

et al. 2023

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“…In line with our results, Bechlioulis et al found no effect of combination treatment or any of the treatments alone on cf-PWV. 20 The study was open-label, and patients were at lower CV risk compared with our population.…”

Section: Discussionmentioning

confidence: 94%

“…Some studies found no effect of SGLT2is on arterial stiffness, 20,34,35 including a recent meta‐analysis, 36 while others observed a reduction 19,37 . Similarly, studies of GLP‐1RAs have found reduced arterial stiffness post‐treatment, 19,31,38–40 whereas other studies did not find an effect 20,41 . Differences in study design, populations enrolled, and adjustment for BP may account for some of these differences.…”

Section: Discussionmentioning

confidence: 99%

“…Improvements in arterial stiffness have been proposed to contribute to the CV protection seen with the use of both SGLT2is and GLP‐1RAs 17,18 . However, the existing evidence is inconsistent with limited and conflicting results of combination treatment 19,20 …”

Section: Introductionmentioning

confidence: 99%

“…17,18 However, the existing evidence is inconsistent with limited and conflicting results of combination treatment. 19,20 In the DURATION-8 study, combination treatment with dapagliflozin and exenatide resulted in an additive systolic BP reduction compared with monotherapy. 21 However, data are limited on the effect of combination therapy on 24-h ambulatory BP, which has a stronger association with CV risk and mortality compared with office BP.…”

Section: Introductionmentioning

confidence: 99%

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Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32‐week randomized trial

Vernstrøm,

Gullaksen,

Sørensen

et al. 2024

Diabetes Obesity Metabolism

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AimDespite the increasing use of combination treatment with sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide‐1 receptor agonists, data are limited on the effects of combination treatment on markers of cardiovascular disease. This study aimed to investigate the effect of empagliflozin, semaglutide, and their combination on vascular function.Materials and MethodsIn total, 120 patients with type 2 diabetes were randomized into four groups (n = 30 in each) for 32 weeks: placebo, semaglutide, empagliflozin, and their combination. The study had two co‐primary outcomes: change in arterial stiffness and kidney oxygenation. This paper reports on arterial stiffness assessed as carotid‐femoral pulse wave velocity. Secondary outcomes included 24‐h blood pressure (BP), 24‐h central BP, urinary albumin to creatinine ratio and glycaemic control assessed by both continuous glucose monitoring and glycated haemoglobin.ResultsThe carotid‐femoral pulse wave velocity did not change significantly in any of the groups compared with placebo. Twenty‐four‐hour systolic BP was reduced by 10 mmHg (95% CI 6–14), p < .001 in the combination group, significantly superior to both placebo and monotherapy (p < .05). Combination treatment increased glycaemic time in range from 72% at baseline to 91% at week 32, p < .001, without increasing time below range. The urinary albumin to creatinine ratio decreased by 36% (95% CI 4–57), p = .03 in the combination group compared with placebo.ConclusionsEmpagliflozin, semaglutide, or their combination did not reduce arterial stiffness. Combination treatment showed a substantial and clinically important reduction in 24‐h systolic BP compared with either treatment alone. Combination treatment increased glycaemic time in range without increasing the risk of hypoglycaemia.

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GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy

Scheen

2024

Drugs

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The effect of SGLT2 inhibitors, GLP1 agonists, and their sequential combination on cardiometabolic parameters: A randomized, prospective, intervention study

Cited by 15 publications

References 43 publications

Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies

Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies

Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32‐week randomized trial

GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy

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