Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2024; 15(3): 463-474
Published online Mar 15, 2024. doi: 10.4239/wjd.v15.i3.463
Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience
Lubna Islam, Dhanya Jose, Mohammed Alkhalifah, Dania Blaibel, Vishnu Chandrabalan, Joseph M Pappachan
Lubna Islam, Mohammed Alkhalifah, Dania Blaibel, Joseph M Pappachan, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
Dhanya Jose, Department of Community Medicine, Goa Medical College, Goa 403202, India
Mohammed Alkhalifah, Department of Family Medicine, King Faisal Specialist Hospital, Riyadh 11564, Saudi Arabia
Vishnu Chandrabalan, Department of Data Science, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
Joseph M Pappachan, Faculty of Science, Manchester Metropolitan University, All Saints Building, Manchester M15 6BH, United Kingdom
Joseph M Pappachan, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
Co-first authors: Lubna Islam and Dhanya Jose.
Author contributions: Islam L, Alkhalifah M, and Blaibel D collected the clinical data; Jose D performed the statistical analysis and wrote the initial draft of the manuscript; Islam L performed the literature review, and interpretation of relevant data following statistical analysis; Islam L and Jose D helped revision and figure preparation for the paper and share the first authorship of the work; Alkhalifah M, Blaibel D, and Chandrabalan V contributed to the work with additional literature review and revision of the article critically for important intellectual content; Chandrabalan V also procured the patient data from the hospital electronic records; Pappachan JM contributed to the conceptual design of the paper and critically supervised the whole drafting, literature review, revision and modifications of the paper including figure construction and is the final author; and all authors have read and approved the final version of the manuscript.
Institutional review board statement: The study was approved by the institutional research committee (No: KB/PB/SE-387/2022).
Informed consent statement: This is a retrospective cohort study performed by review of participants’ electronic clinical records only and therefore, patient consent was not necessary and was not obtained.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Authors are happy to share the data on request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph M Pappachan, MD, FRCP, Academic Editor, Consultant Endocrinologist, Professor, Senior Researcher, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Sharoe Green Lane, Preston PR2 9HT, United Kingdom. drpappachan@yahoo.co.in
Received: October 28, 2023
Peer-review started: October 28, 2023
First decision: December 29, 2023
Revised: January 2, 2024
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: March 15, 2024
Abstract
BACKGROUND

Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a class of drugs with modest antidiabetic efficacy, weight loss effect, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). However, real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.

AIM

To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.

METHODS

We evaluated the comparative efficacy data of 3 SGLT-2i drugs (dapagliflozin, canagliflozin, and empagliflozin) used for treating patients with type 2 diabetes mellitus. Data on the reduction of glycated hemoglobin (HbA1c), body weight, blood pressure (BP), urine albumin creatinine ratio (ACR), and adverse effects were recorded retrospectively.

RESULTS

Data from 467 patients with a median age of 64 (14.8) years, 294 (62.96%) males and 375 (80.5%) Caucasians were analysed. Median diabetes duration was 16.0 (9.0) years, and the duration of SGLT-2i use was 3.6 (2.1) years. SGLT-2i molecules used were dapagliflozin 10 mg (n = 227; 48.6%), canagliflozin 300 mg (n = 160; 34.3%), and empagliflozin 25 mg (n = 80; 17.1). Baseline median (interquartile range) HbA1c in mmol/mol were: dapagliflozin - 78.0 (25.3), canagliflozin - 80.0 (25.5), and empagliflozin - 75.0 (23.5) respectively. The respective median HbA1c reduction at 12 months and the latest review (just prior to the study) were: 66.5 (22.8) & 69.0 (24.0), 67.0 (16.3) & 66.0 (28.0), and 67.0 (22.5) & 66.5 (25.8) respectively (P < 0.001 for all comparisons from baseline). Significant improvements in body weight (in kilograms) from baseline to study end were noticed with dapagliflozin - 101 (29.5) to 92.2 (25.6), and canagliflozin 100 (28.3) to 95.3 (27.5) only. Significant reductions in median systolic and diastolic BP, from 144 (21) mmHg to 139 (23) mmHg; (P = 0.015), and from 82 (16) mmHg to 78 (19) mmHg; (P < 0.001) respectively were also observed. A significant reduction of microalbuminuria was observed with canagliflozin only [ACR 14.6 (42.6) at baseline to 8.9 (23.7) at the study end; P = 0.043]. Adverse effects of SGLT-2i were as follows: genital thrush and urinary infection - 20 (8.8%) & 17 (7.5%) with dapagliflozin; 9 (5.6%) & 5 (3.13%) with canagliflozin; and 4 (5%) & 4 (5%) with empagliflozin. Diabetic ketoacidosis was observed in 4 (1.8%) with dapagliflozin and 1 (0.63%) with canagliflozin.

CONCLUSION

Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c, body weight, and better than those reported in RCTs, with low side effect profiles. A review of large-scale real-world data is needed to inform better clinical practice decision making.

Keywords: Sodium glucose cotransporter-2 inhibitors, Empagliflozin, Canagliflozin, Dapagliflozin, Type 2 diabetes mellitus, Cardiovascular disease, Albumin creatinine ratio, Diabesity

Core Tip: Treatment of type 2 diabetes mellitus with sodium glucose cotransporter-2 inhibitors (SGLT-2i) is associated with significant glycated hemoglobin (HbA1c) reduction, body weight loss, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). Our real-world data analysis of the efficacy and safety of individual SGLT-2i revealed better reduction of HbA1c with dapagliflozin, canagliflozin, and empagliflozin, while better body weight reduction was seen only with dapagliflozin and canagliflozin when compared to RCTs. Blood pressure reduction, and side effect profiles were comparable to previous studies. A significant improvement of albuminuria was obvious only with canagliflozin, presumably because of the low number of participants in this study. Analyses of various large-scale real-world data are expected to inform better clinical practice decision making in future.