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Medications used for diabetes mellitus include insulin, sulfonylureas and other insulin secretagogues, alpha-glucosidase inhibitors (acarbose, miglitol), biguanides (metformin), thiazolidinediones (pioglitazone, rosiglitazone), sodium glucose transporter (SGLT2) inhibitors, and peptide analogs (pramlintide, exenatide) or enhancers (sitagliptin) (see Chapter 27). Of these, insulin and the insulin secretagogues are the most likely to cause hypoglycemia. Metformin can cause lactic acidosis, especially in patients with impaired kidney function or after intentional drug overdose. Euglycemic diabetic ketoacidosis has been reported with SGLT2 use. Table 27–4 lists the duration of hypoglycemic effect of oral hypoglycemic agents and Table 27–5 the extent and duration of various types of insulins.


Hypoglycemia may occur quickly after injection of short-acting insulins or may be delayed and prolonged, especially if a large amount has been injected into a single area, creating a “depot” effect. Hypoglycemia after sulfonylurea ingestion is usually apparent within a few hours but may be delayed several hours, especially if food or glucose-containing fluids have been given.


Give sugar and carbohydrate-containing food or liquids by mouth, or intravenous dextrose if the patient is unable to swallow safely. For severe hypoglycemia, start with D50W, 50 mL intravenously (25 g dextrose); repeat, if needed. Follow up with dextrose-containing intravenous fluids (D5W or D10W) to maintain a blood glucose greater than 70–80 mg/dL.

For hypoglycemia caused by sulfonylureas and related insulin secretagogues, consider use of octreotide, a synthetic somatostatin analog that blocks pancreatic insulin release. A dose of 50–100 mcg octreotide subcutaneously every 6–12 hours can reduce the need for exogenous dextrose and prevent rebound hypoglycemia from excessive dextrose dosing.

Admit all patients with symptomatic hypoglycemia after sulfonylurea overdose. Observe asymptomatic overdose patients for at least 12 hours.

Consider hemodialysis for patients with metformin overdose accompanied by severe lactic acidosis (lactate greater than 20 mmol/L or pH < 7.0).

Baumgartner  K  et al. Toxicology of medications for diabetes mellitus. Crit Care Clin. 2021;37:577.
[PubMed: 34053707]  
Razavi-Nematollahi  L  et al. Adverse effects of glycemia-lowering medications in type 2 diabetes. Curr Diab Rep. 2019;19:132.
[PubMed: 31748838]  

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