When is intramuscular (IM) insulin appropriate for treating diabetic ketoacidosis (DKA) compared to intravenous (IV) or subcutaneous (SC) routes?

Intramuscular Insulin for Diabetic Ketoacidosis

Intramuscular insulin is not recommended as a primary route for treating DKA in modern practice; intravenous regular insulin remains the standard of care for moderate-to-severe DKA, while subcutaneous rapid-acting insulin analogs are an acceptable alternative for mild-to-moderate uncomplicated DKA in hemodynamically stable patients. 1, 2

Historical Context and Evidence

IM insulin was studied in the 1970s as an alternative route when IV access was difficult or unavailable. A 1977 randomized trial demonstrated that IM insulin required more frequent repeat dosing (6 of 15 patients needed additional priming doses) compared to IV (2 of 15) or subcutaneous routes (3 of 15), and showed slower initial glucose and ketone reduction in the first 2 hours compared to IV administration 3. After the initial 2-hour period, there were no significant differences in time to DKA resolution between routes 3.

Current Standard Routes of Insulin Administration

Intravenous Insulin (First-Line for Moderate-Severe DKA)

For critically ill, mentally obtunded, or hemodynamically unstable patients with moderate-to-severe DKA, continuous IV regular insulin at 0.1 units/kg/hour is the standard of care. 1, 2

• Begin with IV bolus of 0.1-0.15 units/kg regular insulin, followed by continuous infusion at 0.1 units/kg/hour 1, 2
• Target glucose decline of 50-75 mg/dL per hour 1, 2
• If glucose fails to fall by ≥50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate hourly until steady decline achieved 1, 2
• Continue insulin infusion until complete DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L, glucose <200 mg/dL) regardless of glucose level 1, 2

Subcutaneous Rapid-Acting Insulin Analogs (Alternative for Mild-Moderate DKA)

For hemodynamically stable, alert patients with mild-to-moderate uncomplicated DKA, subcutaneous rapid-acting insulin analogs (lispro or aspart) combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin. 1, 4, 5

• Administer 0.15-0.2 units/kg subcutaneously every 1-2 hours 1, 6
• Multiple randomized trials show no difference in time to DKA resolution compared to IV regular insulin (mean 10-11 hours for both routes) 6, 7
• This approach eliminates the need for ICU admission in carefully selected patients 5
• Requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1

Why IM Insulin Is Not Currently Recommended

Practical Limitations

• No contemporary guidelines from the American Diabetes Association or American Association of Clinical Endocrinologists recommend IM insulin as a primary route for DKA management 1, 2
• IM route offers no advantage over subcutaneous rapid-acting analogs, which have become the preferred non-IV alternative 4, 5
• The 1977 study showing IM efficacy predates the development of rapid-acting insulin analogs (lispro, aspart), which have superior pharmacokinetics for subcutaneous administration 3, 4

Superior Alternatives Available

• IV insulin provides the most rapid and titratable glucose control for severe DKA 1, 2
• Subcutaneous rapid-acting analogs are simpler, less painful, and equally effective for mild-moderate DKA 4, 5, 6
• Modern evidence supports a binary choice: IV for severe/complicated DKA versus subcutaneous rapid-acting analogs for mild-moderate uncomplicated DKA 1, 7

Critical Safety Considerations Before Any Insulin Route

Potassium Management (Class A Evidence)

Never initiate insulin by any route if serum potassium is <3.3 mEq/L; this is an absolute contraindication that can cause life-threatening arrhythmias and cardiac arrest. 1, 2

• If K⁺ <3.3 mEq/L: Hold insulin and aggressively replace potassium at 20-40 mEq/hour until K⁺ ≥3.3 mEq/L 1, 2
• If K⁺ 3.3-5.5 mEq/L: Start insulin and add 20-30 mEq potassium per liter of IV fluid (2/3 KCl, 1/3 KPO₄) once adequate urine output confirmed 1, 2
• If K⁺ >5.5 mEq/L: Start insulin immediately but withhold potassium supplementation until level falls below 5.5 mEq/L 1, 2
• Target serum potassium 4-5 mEq/L throughout treatment 1, 2

Fluid Resuscitation

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour regardless of insulin route 1, 2
• When glucose falls to 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl while continuing insulin to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 2

Common Pitfalls to Avoid

• Never stop insulin when glucose reaches 250 mg/dL—instead add dextrose to IV fluids while maintaining insulin infusion to clear ketones 1
• Never discontinue IV insulin without administering basal subcutaneous insulin 2-4 hours earlier—this causes rebound hyperglycemia and recurrent DKA 1, 2
• Do not rely on urine ketones for monitoring; use serum β-hydroxybutyrate when available 1
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1