Jonathan V. Mui1  · Lifang Li2  · Oscar Hou In Chou1,3  ·iD. Nida Azfar1  · Athena Lee1,4 · Jeremy Hui1,3 · Sharen Lee1  · Gary Tse1,5,6,8,9 · Jiandong Zhou7

Received: 29 October 2022 / Accepted: 24 February 2023 / Published online: 31 March 2023 © The Author(s) 2023

Abstract

Introduction The risk of new onset depression associated with sodium-glucose co-transporter 2 inhibitor (SGLT2I) use in patients with type 2 diabetes mellitus (T2DM) remains unclear. This study investigated the risk of new onset depression between SGLT2I and dipeptidyl peptidase 4 inhibitor (DPP4I) users.

Methods This was a population-based cohort study of T2DM patients in Hong Kong between January 1st, 2015, and December 31st, 2019. T2DM patients over 18 with either SGLT2I or DPP4I use were included. 1:1 propensity-score matching using the nearest-neighbour method was conducted based on demographics, past comorbidities and non-DPP4I/SGLT2I medication use. Cox regression analysis models were used to identify significant predictors for new onset depression.

Results The study cohort included a total of 18,309 SGLT2I users and 37,269 DPP4I users (55.57% male, mean age: 63.5±12.9 years) with a median follow-up duration of 5.56 (IQR: 5.23–5.8) years. After propensity score matching, SGLT2I use was associated with a lower risk of new onset depression compared to DPP4I use (HR: 0.52, 95% CI: [0.35, 0.77], P=0.0011). These findings were confirmed by Cox multivariable analysis and sensitive analyses.

Conclusion SGLT2I use is associated with significantly lower risk of depression compared to DPP4 use in T2DM patients using propensity score matching and Cox regression analyses.

Keywords Type 2 diabetes · Depression · Anti-diabetic medication · SGLT2 inhibitor · DPP4 inhibitor

Jonathan V. Mui and Lifang Li are joint first authors.

“This article belongs to the topical collection “Health Education and Psycho-Social Aspects, managed by Massimo Porta and Marina Trento”.

Gary Tse

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* Jiandong Zhou

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1 Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China

2 Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

3 Department of Medicine, The University of Hong Kong, Hong Kong, China

4 Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

5 Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China

6 Kent and Medway Medical School, Canterbury, UK

7 Nufeld Department of Medicine, University of Oxford, Oxford, UK

8 School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China

9 Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China

D.Caldeira1,2,3· M. Alves3,4,5 · J. J. Ferreira3,4 · F. J. Pinto1,2

Received: 5 October 2022 / Accepted: 29 December 2022 / Published online: 18 January 2023 © The Author(s) 2023

D. Caldeira

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1 Centro Cardiovascular da Universidade de Lisboa–CCUL (CCUL@RISE), Faculdade de Medicina, CEMBE, CAML, Universidade de Lisboa, Lisbon, Portugal

2 Serviço de Cardiologia, Hospital Universitário de Santa Maria–CHULN, Lisbon, Portugal

3 Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

4 Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal

5 Serviço de Medicina III, Hospital Pulido Valente, CHLN, Lisbon, Portugal

Abstract

Purpose Aspirin use among patients with diabetes in primary prevention is still a matter of debate. We aimed to evaluate the potential cardiovascular risk benefit of aspirin in primary prevention, using data from a contemporary cohort.

Methods Retrospective analysis of the VITAL cohort with>20,000 individuals at primary prevention who were followed for a median of 5.3 years. The population was evaluated according to the baseline diabetes status, and then aspirin use was evaluated among diabetic patients. Cox regression models were used to estimate the risks of mortality and cardiovascular outcomes. The estimates were reported using adjusted hazard ratio (HR) and 95% confidence intervals (95%CI).

Results Diabetic patients (n=3549; 13.7%) showed to increase the risk of all-cause mortality (HR 1.61, 95%CI 1.33–1.94), and major adverse cardiovascular events (MACE) (HR 1.36 95%CI 1.11–1.68) than non-diabetic population. Diabetic patients taking aspirin were older, more frequently man, hypertensive, current users of statins, and current smokers compared with diabetic patients who did not use aspirin at baseline. There was no difference between diabetic aspirin users and non-users regarding all-cause mortality (HR 0.80, 95%CI 0.59, 1.10), MACE (HR 0.92, 95%CI 0.64, 1.33), coronary heart disease (HR 0.98, 95%CI 0.67, 1.43), or stroke (HR 0.87, 95%CI 0.48, 1.58).

Conclusions The VITAL data confirmed diabetes as an important risk factor for cardiovascular events in a contemporary cohort but did not show cardiovascular benefits of aspirin in primary prevention among people with diabetes who were shown to be at higher risk of cardiovascular events.

Keywords Cardiovascular disease · Primary prevention · Aspirin · Diabetes

AUTHORS

Pam Chen1,2, Nalini Campillo Vilorio3 , Ketan Dhatariya4, 5, William Jeffcoate6 , Ralf Lobmann7 , Caroline McIntosh8 , Alberto Piaggesi9 , John Steinberg10, Prash Vas11, Vijay Viswanathan12, Stephanie Wu13, Fran Game14, on behalf of the International Working Group on the Diabetic Foot

INSTITUTIONS

1 Joondalup Health Campus, Ramsay Healthcare Australia, Joondalup, Western Australia, Australia

2 Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia

3 Department of Diabetology, Diabetic Foot Unit, Plaza de la Salud General Hospital, Santo Domingo, Dominican Republic

4 Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK

5 Norwich Medical School, University of East Anglia, Norwich, UK

6 Retired physician, Nottingham, UK

7 Clinic for Endocrinology, Diabetology and Geriatrics, Klinikum Stuttgart, Stuttgart, Germany

8 Podiatric Medicine, School of Health Sciences, University of Galway, Ireland

9 Diabetic Foot Section, Department of Medicine, University of Pisa, Italy

10 Georgetown University School of Medicine, Washington DC, USA

11 King’s College Hospital NHS Foundation Trust, London, UK

12 MV Hospital for Diabetes and Prof M Viswanathan Diabetes Research Center, Chennai, India

13 Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA

14 University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK