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
. 2023 Mar;60(3):401-411.
doi: 10.1007/s00592-022-02015-6. Epub 2022 Dec 28.

SGLT-2 inhibitors and euglycemic diabetic ketoacidosis/diabetic ketoacidosis in FAERS: a pharmacovigilance assessment

Zhichao He #  1   2 , Kakei Lam #  3 , Wenxia Zhao #  1   2 , Shan Yang #  1   2 , Yu Li  3 , Jiayao Mo  3 , Siyuan Gao  1   2 , Dan Liang  1   2 , Kaifeng Qiu  4   5 , Min Huang  6 , Junyan Wu  7   8
Affiliations

SGLT-2 inhibitors and euglycemic diabetic ketoacidosis/diabetic ketoacidosis in FAERS: a pharmacovigilance assessment

Zhichao He et al. Acta Diabetol. 2023 Mar.

Abstract

Aims: To investigate the main feature and the association between euglycemic diabetic ketoacidosis (euDKA) /diabetic ketoacidosis (DKA) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) from the FDA adverse event reporting system (FAERS).

Methods: Cases of SGLT-2i-associated with euDKA/DKA were extracted from the FAERS database and compared with the reports for other hypoglycemia agents (ATC10 class). Disproportionality analyses used the reporting odds ratio (ROR) and information components (IC). The lower limit of the IC 95% credibility interval for IC > 0 is considered a reported signal, with at least 3 cases.

Results: A total of 10,195 cases of euDKA (n = 1680) and DKA (n = 8515) associated with SGLT-2i were identified from the FAERS. The SGLT-2i was associated with higher reporting of euDKA and DKA compared to other hypoglycemia agents (ROR = 16.69 [95% CI 14.89-18.70], IC = 3.27 [95% CI 2.91-3.66] for euDKA; ROR = 16.44 [95% CI 15.72-17.20], IC = 3.19 [95% CI 3.05-3.34] for DKA). In available data, the median onset time of euDKA/DKA was 31 days, and canagliflozin had the longest onset time (96.5 days for euDKA and 75 days for DKA) compared with dapagliflozin and empagliflozin (p < 0.05). Male patients predominate in euDKA (51.9%), and female patients predominate in DKA (53.7%). Most patients discontinue the treatment (95.5% for euDKA, 93.9% for DKA), and approximately 49.0% (n = 3658) of patients had symptomatic remission after discontinuation of SGLT-2i, and 2.3% (n = 173) of patients had no remission. About 75.6% (n = 6126) of patients need hospitalization after euDKA/DKA.

Conclusions: Post-marketing data showed that SGLT-2i was significantly associated with higher reporting of euDKA/DKA. Although euDKA/DKA is rare, clinicians should be aware of SGLT-2i-associated euDKA/DKA events.

Keywords: Diabetic ketoacidosis; Euglycemic diabetic ketoacidosis; FAERS; Sodium-dependent glucose transporters 2 inhibitors.

PubMed Disclaimer

References

    1. Brown E, Rajeev SP, Cuthbertson DJ, Wilding JPH (2019) A review of the mechanism of action, metabolic profile and haemodynamic effects of sodium-glucose co-transporter-2 inhibitors. Diabetes Obes Metab 21(Suppl):2. https://doi.org/10.1111/dom.13650 - DOI
    1. Zelniker TA, Braunwald E (2018) Cardiac and renal effects of sodium-glucose co-transporter 2 inhibitors in diabetes: JACC state-of-the-art review. J AM Coll Cardiol 72:1845–1855. https://doi.org/10.1016/j.jacc.2018.06.040 - DOI - PubMed
    1. Furtado RHM, Bonaca MP, Raz I et al (2019) Dapagliflozin and in cardiovascular outcomes patients with type 2 diabetes mellitus and previous myocardial infarction. Circulation 139:2516–2527. https://doi.org/10.1161/CIRCULATIONAHA.119.039996 - DOI - PubMed
    1. Mahaffey KW, Neal B, Perkovic V et al (2018) Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program (Canagliflozin cardiovascular assessment study). Circulation 137:323–334. https://doi.org/10.1161/CIRCULATIONAHA.117.032038 - DOI - PubMed - PMC
    1. McGuire DK, Zinman B, Inzucchi SE et al (2020) Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial Lancet. Diabetes Endocrinol 8:949–959. https://doi.org/10.1016/S2213-8587(20)30344-2 - DOI

MeSH terms

Substances

LinkOut - more resources