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

Aris Bechlioulis; Georgios Markozannes; Ifigeneia Chionidi; Evangelos Liberopoulos; Katerina K Naka; Evangelia E Ntzani; Stavros Liatis; Manfredi Rizzo; Evangelos C Rizos

doi:10.1016/j.jdiacomp.2023.108436

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

J Diabetes Complications. 2023 Apr;37(4):108436. doi: 10.1016/j.jdiacomp.2023.108436. Epub 2023 Feb 23.

Authors

Aris Bechlioulis¹, Georgios Markozannes², Ifigeneia Chionidi³, Evangelos Liberopoulos⁴, Katerina K Naka¹, Evangelia E Ntzani⁵, Stavros Liatis⁴, Manfredi Rizzo⁶, Evangelos C Rizos⁷

Affiliations

¹ 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, Ioannina, Greece.
² Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
³ Diabetes Outpatient Clinic, University Hospital of Ioannina, Ioannina, Greece.
⁴ First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁵ Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Center for Evidence-Based Medicine, Department of Health Services, Policy and Practice, School of Public Health, Brown University, Providence, RI, USA.
⁶ Department of Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, Palermo, Italy.
⁷ Department of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus. Electronic address: vagrizos@gmail.com.

PMID: 36842186
DOI: 10.1016/j.jdiacomp.2023.108436

Abstract

Background: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We aim to compare the effect of empagliflozin, liraglutide and their sequential combination on arterial stiffness indices in patients with type 2 diabetes (T2D).

Methods: This was a randomized single blind study evaluating the effect of empagliflozin vs liraglutide in adult patients with T2D. Patients were randomized to liraglutide titrated gradually to 1.8 mg or empagliflozin 25 mg in 1:1 ratio. Three months later empagliflozin was added to the liraglutide group, and liraglutide was added to the empagliflozin group. Patients were assessed with non-invasive tests for arterial stiffness (i.e., carotid-femoral PWV and AIx of aortic pressure) at baseline, 3-month and 9-month visits (final visit was extended for 3 months from the initial design due to Covid 19 pandemic). The primary outcome was the between-group difference of PWV change (ΔPWV) and ΔAIx at 3 months. Secondary outcomes included the between-group difference of ΔPWV and ΔAIx at 9 months, as well as the ΔPWV and ΔAIx between baseline and 9-month visit when total study population was assessed.

Results: A total of 62 patients with T2D (30 started liraglutide; 32 empagliflozin, mean age 63 years, 25 % with established cardiovascular disease) participated in the study. We failed to show any significant between-group differences of ΔPWV and ΔΑΙx at 3 and 9 months, as well as between-group difference of ΔPWV and ΔAIx for the total study population between baseline and 9-month visit. In contrast, systemic vascular resistance and lipoprotein(a) levels improved, showing better results with liraglutide than empagliflozin. Favorable effects were also observed on body weight, body mass index, body and visceral fat, blood pressure, HbA1c, and uric acid levels.

Conclusion: No evidence of a favorable change in arterial stiffness indices was seen with empagliflozin or liraglutide or their combination in this study. Well-designed powerful studies are needed to address any potential effects on arterial stiffness in selected populations.

Keywords: Arterial stiffness; Diabetes; Empagliflozin; GLP1 agonist; Liraglutide; Pulse wave velocity; SGLT2 inhibitor.

Publication types

Randomized Controlled Trial

MeSH terms

COVID-19* / complications
Cardiovascular Diseases* / complications
Cardiovascular Diseases* / epidemiology
Cardiovascular Diseases* / prevention & control
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Humans
Liraglutide / adverse effects
Middle Aged
Prospective Studies
Pulse Wave Analysis
Single-Blind Method
Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
Vascular Stiffness*

Substances

empagliflozin
Liraglutide
Sodium-Glucose Transporter 2 Inhibitors
SLC5A2 protein, human