Frontiers in endocrinology · 2026
Case Report: Early-onset euglycemic diabetic ketoacidosis following henagliflozin initiation in a treatment-naive patient.
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Cai Jing, Fu Tiantian, Tan Cuixia
Аннотация
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with euglycemic diabetic ketoacidosis (euDKA), typically occurring after ≥2 weeks of therapy in the setting of intercurrent illness or surgical stress. The risk of early-onset euDKA in treatment-naive patients-those without prior glucose-lowering therapy or established metabolic stability-remains poorly characterized. We describe a case of severe euDKA occurring within 4 days of SGLT2 inhibitor initiation, precipitated solely by metformin-induced gastrointestinal adverse effects.
CASE PRESENTATION: A 40-year-old woman with newly diagnosed type 2 diabetes (HbA1c 12.9%) was initiated on metformin, henagliflozin (SGLT2 inhibitor), and chiglitazar. Within 24 hours, she developed nausea and vomiting attributed to metformin intolerance. Despite progressive symptoms and minimal oral intake over 72 hours, she continued all medications without seeking medical care. On day 4, she presented with severe high-anion-gap metabolic acidosis (pH 7.043, bicarbonate 6.5 mmol/L), ketonemia (β-hydroxybutyrate 5.6 mmol/L), and plasma glucose 8.5 mmol/L-consistent with euDKA. Management included intravenous dextrose, insulin infusion, and fluid resuscitation, with resolution by day 3. The patient was discharged on basal insulin, metformin, and chiglitazar (SGLT2 inhibitor discontinued), with no recurrence at 4-week follow-up.
CONCLUSION: In treatment-naive patients initiating SGLT2 inhibitor-based combination therapy, common metformin-associated gastrointestinal symptoms (10-30% of initiants) can precipitate severe euDKA within days through reduced oral intake and dehydration. Although these are well-recognized precipitants, this case underscores the vulnerability of treatment-naive patients to routine adverse effects during the critical initial phase, highlighting the need for stepwise drug initiation, explicit sick-day education, and scheduled early follow-up.
CASE PRESENTATION: A 40-year-old woman with newly diagnosed type 2 diabetes (HbA1c 12.9%) was initiated on metformin, henagliflozin (SGLT2 inhibitor), and chiglitazar. Within 24 hours, she developed nausea and vomiting attributed to metformin intolerance. Despite progressive symptoms and minimal oral intake over 72 hours, she continued all medications without seeking medical care. On day 4, she presented with severe high-anion-gap metabolic acidosis (pH 7.043, bicarbonate 6.5 mmol/L), ketonemia (β-hydroxybutyrate 5.6 mmol/L), and plasma glucose 8.5 mmol/L-consistent with euDKA. Management included intravenous dextrose, insulin infusion, and fluid resuscitation, with resolution by day 3. The patient was discharged on basal insulin, metformin, and chiglitazar (SGLT2 inhibitor discontinued), with no recurrence at 4-week follow-up.
CONCLUSION: In treatment-naive patients initiating SGLT2 inhibitor-based combination therapy, common metformin-associated gastrointestinal symptoms (10-30% of initiants) can precipitate severe euDKA within days through reduced oral intake and dehydration. Although these are well-recognized precipitants, this case underscores the vulnerability of treatment-naive patients to routine adverse effects during the critical initial phase, highlighting the need for stepwise drug initiation, explicit sick-day education, and scheduled early follow-up.