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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Clinical Diabetes
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1453067

Risk of diabetic ketoacidosis caused by sodium glucose cotransporter-2 inhibitors in patients with type 1 diabetes: a systematic review and network meta-analysis of randomized controlled trials

Provisionally accepted
Ying Liu Ying Liu 1Shiwen Yang Shiwen Yang 2Aidou Jiang Aidou Jiang 1Zou Dan Zou Dan 1Chen Zhao Yang Chen Zhao Yang 1Na Su Na Su 1,3*
  • 1 Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
  • 2 Department of Pharmacy, Jiangxi Mental Health Center, Nanchang, China
  • 3 West China School of Pharmacy, Sichuan University, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    The benefits of sodium-glucose-cotransporter-2 (SGLT2) inhibitors in the treatment of type 1 diabetes mellitus (T1DM) have been demonstrated, but the occurrence of diabetic ketoacidosis (DKA) limits their use. The risk of DKA associated with different doses of SGLT2 in the treatment of T1DM is unknown. We conducted a network meta-analysis to evaluate the incidence of DKA at different doses in the treatment of T1DM.: We searched electronic databases and clinical trial registries, including PubMed, Embase (Ovid SP), the Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov, for randomized controlled trials (RCTs) concerning SGLT2 inhibitors in patients with T1DM from inception to December 2023. Literature screening, quality assessment and data extraction were carried out independently by 2 researchers based on the inclusion and exclusion criteria, and statistical analysis was performed using Stata 15.1 software and R 4.1.3.Nineteen clinical studies and one clinical trial were ultimately included. The study involved five different SGLT2 inhibitors. The incidence of DKA in dapagliflozin 5 mg (OR: 2.57, 95% CI: 1.04 to 6.33; P<0.00001), empagliflozin 10 mg (OR: 2.68, 95% CI: 1.11 to 6.49; P<0.00001), sogliflozin 200mg (OR: 4.04, 95% CI: 1.15 to14.18; P<0.00001) and sogliflozin 400mg (OR: 5.96, 95% CI: 2.06 to17.20; P<0.00001) were higher than for the placebo. According to the P scores, SGLT2 inhibitors triggered a lower incidence of DKA than did the placebo.Treatment with 300 mg canagliflozin had the lowest incidence of DKA (P score = 0.8563).According to our study, 5 mg dapagliflozin,10 mg empagliflozin 200mg sogliflozin and 400mg sogliflozin resulted in DKA when adjunctive insulin was used to treat T1DM. Other SGLT2 inhibitors seem to be safe. However, SGLT2 inhibitors for treating T1DM are off label in China, and adverse reactions should be closely monitored during administration.

    Keywords: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors, The risk of diabetic ketoacidosis, type 1 diabetes mellitus, Network meta-analysis, Placebo control

    Received: 22 Jun 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Liu, Yang, Jiang, Dan, Zhao Yang and Su. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Na Su, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China

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