Treatment of hyperkalemia with intravenous insulin-dextrose is associated with a risk of hypoglycemia. We aimed to determine the factors associated with hypoglycemia (glucose < 3.9 mmol/L, or < 70 mg/dL) and the critical time window with the highest incidence. In a retrospective cohort study in a tertiary hospital network, we included 421 adult patients with a serum potassium ≥ 6.0 mmol/L who received insulin-dextrose treatment. The mean age was 70 years with 62% male predominance. The prevalence of diabetes was 60%, and 70% had chronic kidney disease (eGFR < 60 ml/min/1.73 m2). The incidence of hypoglycemia was 21%. In a multivariable logistic regression model, the factors independently associated with hypoglycemia were: body mass index (per 5 kg/m2, OR 0.85, 95% CI: 0.69-0.99, P = 0.04), eGFR < 60 mL/min/1.73 m2 (OR 2.47, 95% CI: 1.32-4.63, P = 0.005), diabetes (OR 0.57, 95% CI 0.33-0.98, P = 0.043), pre-treatment blood glucose (OR 0.84, 95% CI: 0.77-0.91, P < 0.001), and treatment in the emergency department compared to other locations (OR 2.53, 95% CI: 1.49-4.31, P = 0.001). Hypoglycemia occurred most frequently between 60 and 150 min, with a peak at 90 min. Understanding the factors associated with hypoglycemia and the critical window of risk is essential for the development of preventive strategies.