Background: In insulin-treated patients (pts) with T2DM, untreated severe hypoglycemia (SH) can be life-threatening. We used a healthcare claims database (db) to identify less established SH risk factors in this group. Methods: Adults with T2DM and ≥1 insulin claim (2012-2018) were identified in IQVIA’s PharMetrics® Plus db. Cases with SH were matched to controls using incidence density sampling and exact matched on well‑known factors (age, sulfonylurea pharmacy claim, prior SH, renal disease). A conditional logistic regression model tested associations between potential risk factors and SH occurrence. Results: In 3153 cases/3153 matched controls, mean ± SD age was 56.2 ± 10.9 years. Identified risk factors included pregnancy (odds ratio for exposure ≤1 mo before SH = 3.2, 95% CI 1.7-6.0) and pharmacy claims: short-acting insulin (2.2, 1.6-3.1), rapid-acting insulin (1.5, 1.3-1.7), anxiolytics (1.5, 1.2-1.9), antipsychotics (1.6, 1.1-2.2), corticosteroids (1.4, 1.1-1.7), opioids (1.4, 1.2-1.6), β-adrenergic agonists (1.4, 1.1-1.9). Higher comorbidity score, alcohol abuse and certain comorbidities also raised SH risk (Fig 1). Conclusion: Acknowledging limitations of claims db analyses, our study identified certain comorbidities and medications (primarily within 1 mo of SH) as additional risk factors for SH. Such data may help facilitate interventions for pts with T2DM at increased SH risk. Disclosure J. Settles: Employee; Self; Eli Lilly and Company. C. J. Child: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Gorritz: Consultant; Self; Amgen Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Otsuka America Pharmaceutical, Inc., Takeda Pharmaceutical Co. J. K. Multani: Other Relationship; Self; Eli Lilly and Company. C. Mcguiness: Research Support; Self; AbbVie Inc., Allergan plc, Amgen Inc., Astellas Pharma Inc., Eli Lilly and Company, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Sanofi, Takeda Pharmaceutical Co. R. Wade: Research Support; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company