Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Mar 7;23(1):296.
doi: 10.1186/s12967-025-06312-w.

Unveiling the benefits of Vitamin D3 with SGLT-2 inhibitors for hypertensive obese obstructive sleep apnea patients

Huai Heng Loh  1   2 , Siow Phing Tay  3 , Ai Jiun Koa  3 , Mei Ching Yong  4 , Asri Said  3 , Chee Shee Chai  3 , Natasya Marliana Abdul Malik  3 , Anselm Ting Su  3 , Bonnie Bao Chee Tang  3 , Florence Hui Sieng Tan  4 , Norlela Sukor  5   6
Affiliations
Randomized Controlled Trial

Unveiling the benefits of Vitamin D3 with SGLT-2 inhibitors for hypertensive obese obstructive sleep apnea patients

Huai Heng Loh et al. J Transl Med. .

Abstract

Background: Obstructive sleep apnea (OSA) is associated with poorer quality of life (QoL) and increased cardiovascular risks, which may be exacerbated by hypovitaminosis D. Sodium glucose transporter-2 inhibitor (SGLT2i) provides cardiovascular benefits beyond glycemic control. As vitamin D3 and SGLT2i act through different pathways with similar mechanisms in improving cardio-metabolic health, this study aimed to investigate the synergistic effects of this combination therapy in improving these parameters and QoL in hypertensive obese OSA patients.

Methods: Patients who fulfilled the study criteria were randomized to receive: (i) Dapagliflozin, (ii) vitamin D3, (iii) Dapagliflozin plus vitamin D3, or (iv) no treatment, for 16 weeks. The parameters evaluated included anthropometric measurements, uric acid, HbA1c, lipid profile, steatotic liver disease grade, plasma aldosterone concentration, plasma renin concentration, ultrasound flow-mediated dilatation of brachial artery, hsCRP, heart rate variability (HRV), Epworth Sleepiness Scale (ESS), and QoL scores.

Results: A total of 163 patients were recruited and 153 completed the study. The combination of vitamin D3 and Dapagliflozin treatment led to significant improvements in metabolic parameters and nocturnal heart rates, and prevented deterioration of HRV, with healthier HRV at the end of study visit compared to the control group. Only the combination group exhibited improvements in both ESS and QoL scores.

Conclusions: This is the first study to demonstrate beneficial effects of combining vitamin D3 and SGLT2i in cardio-metabolic outcomes and QoL in hypertensive obese OSA patients. These findings highlight the potential of this combination therapy in addressing the cardio-metabolic challenges and QoL in this patient population.

Trials registration: NCT06690723. Registered 10 October 2024-Retrospectively registered, https://register.

Clinicaltrials: gov/prs/beta/studies/S000EWGF00000085/recordSummary.

Keywords: Cardiovascular; Dapagliflozin; Endothelial function; Epworth Sleepiness Scale; Heart rate variability.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was provided by Medical Research Ethical Committee of Malaysia (NMRR-21-1472-60812) and UNIMAS Medical Ethics Committee (UNIMAS/TNC(PI)/09-65/01). All patients gave written informed consent. Consent for publication: Not applicable. Competing interests: None declared.

Figures

Fig. 1
Fig. 1
a Changes of sympathetic nervous system index with treatment among intervention groups. b Changes of parasympathetic nervous system index with treatment among intervention groups. c Changes of SDNN with treatment among intervention groups. d Changes of RMSSD with treatment among intervention groups. e Changes of average heart rate with treatment among intervention groups
Fig. 1
Fig. 1
a Changes of sympathetic nervous system index with treatment among intervention groups. b Changes of parasympathetic nervous system index with treatment among intervention groups. c Changes of SDNN with treatment among intervention groups. d Changes of RMSSD with treatment among intervention groups. e Changes of average heart rate with treatment among intervention groups
Fig. 1
Fig. 1
a Changes of sympathetic nervous system index with treatment among intervention groups. b Changes of parasympathetic nervous system index with treatment among intervention groups. c Changes of SDNN with treatment among intervention groups. d Changes of RMSSD with treatment among intervention groups. e Changes of average heart rate with treatment among intervention groups
See this image and copyright information in PMC

References

    1. Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015;3(4):310–8. - PMC - PubMed
    1. Zdravkovic M, Popadic V, Klasnja S, Milic N, Rajovic N, Divac A, et al. Obstructive sleep apnea and cardiovascular risk: the role of dyslipidemia, inflammation, and obesity. Front Pharmacol. 2022;13: 898072. - PMC - PubMed
    1. Floras JS. Sleep apnea and cardiovascular disease: an enigmatic risk factor. Circ Res. 2018;122(12):1741–64. - PubMed
    1. Lal C, Weaver TE, Bae CJ, Strohl KP. Excessive daytime sleepiness in obstructive sleep apnea. Mechanisms and clinical management. Ann Am Thorac Soc. 2021;18(5):757–68. - PMC - PubMed
    1. Bjornsdottir E, Keenan BT, Eysteinsdottir B, Arnardottir ES, Janson C, Gislason T, et al. Quality of life among untreated sleep apnea patients compared with the general population and changes after treatment with positive airway pressure. J Sleep Res. 2015;24(3):328–38. - PMC - PubMed

Publication types

MeSH terms

Associated data