EUGLYCEMIC DIABETIC KETOACIDOSIS ASSOCIATED WITH SGLT2 INHIBITORS IN NON-PERIOPERATIVE SETTINGS: A SYSTEMATIC REVIEW

Abstract

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Sodium–glucose cotransporter-2 (SGLT2) inhibitors provide cardiometabolic benefits but may cause euglycemic diabetic ketoacidosis (euDKA), characterized by ketoacidosis without marked hyperglycemia. This study aimed to review the euDKA associated with SGLT2 inhibitors in non-perioperative settings. A systematic search of PubMed, Cochrane Library, and ScienceDirect identified studies involving adults receiving SGLT2 inhibitors. Eight studies published between 2019 and 2024, comprising six cohort studies and two pharmacovigilance analyses, were included and narratively synthesized. EuDKA represented a substantial proportion of SGLT2 inhibitor– associated ketoacidosis cases, with infection, fasting or reduced carbohydrate intake, dehydration, and insulin omission as common triggers. Despite lower glucose levels, metabolic severity, intensive care requirements, and hospital stay were comparable to hyperglycemic diabetic ketoacidosis, while mortality was low. EuDKA is an important complication of SGLT2 inhibitor therapy that may be under recognized, highlighting the need for clinical awareness, early biochemical evaluation, and preventive strategies.


ABSTRAK
Inhibitor sodium–glucose cotransporter-2 (SGLT2) memberikan manfaat kardiometabolik, tetapi dapat menyebabkan ketoasidosis diabetik euglikemik (euDKA), yaitu ketoasidosis tanpa hiperglikemia yang bermakna. Penelitian ini bertujuan untuk meninjau kejadian dan karakteristik euDKA terkait inhibitor SGLT2 pada kondisi non-perioperatif. Penelusuran sistematis dilakukan pada PubMed, Cochrane Library, dan Science Direct terhadap studi pada pasien dewasa. Delapan studi yang dipublikasikan pada 2019–2024, terdiri atas enam kohort dan dua analisis farmakovigilans, diikutsertakan dan disintesis secara naratif. EuDKA mencakup proporsi bermakna kasus ketoasidosis terkait SGLT2, dengan pencetus utama berupa infeksi, puasa atau penurunan asupan karbohidrat, dehidrasi, dan penghentian insulin. Meskipun kadar glukosa lebih rendah, tingkat keparahan metabolik, kebutuhan perawatan intensif, dan lama rawat inap sebanding dengan ketoasidosis diabetik hiperglikemik, sedangkan mortalitasnya rendah. EuDKA merupakan komplikasi penting terapi SGLT2 yang dapat terlambat terdiagnosis sehingga diperlukan kewaspadaan klinis, evaluasi biokimia dini, dan pencegahan.