What are the common adverse effects of subcutaneous insulin injections?

Common Adverse Effects of Subcutaneous Insulin Injections

The most common adverse effects of subcutaneous insulin injections are lipohypertrophy (affecting up to 12% of patients), injection site reactions (pain in 47%, bruising in 41%, bleeding in 56%), and hypoglycemia, with proper injection technique and site rotation being critical to minimize these complications. 1

Primary Injection Site Complications

Lipohypertrophy

• Lipohypertrophy is the most common cutaneous complication of insulin therapy, appearing as soft, smooth raised areas several centimeters in breadth at sites of repeated injections. 1, 2
• This complication occurs in approximately 11.8% of patients overall, with significantly higher rates (17.1%) in those using multiple daily injections compared to insulin pump therapy (4.6%). 3
• Lipohypertrophy directly causes erratic insulin absorption, increased glycemic variability, and unexplained hypoglycemic episodes. 1, 2
• Patients with lipohypertrophy require higher insulin doses (median 0.97 U/kg/day) compared to those without (0.78 U/kg/day). 3
• The condition is more frequently reported (18.3%) in patients experiencing frequent hypoglycemia. 3

Lipoatrophy

• Lipoatrophy (loss of subcutaneous fat) has decreased substantially with modern insulin analogs but still occurs, particularly with repeated use of the same injection site. 2, 4
• This complication causes erratic insulin absorption leading to difficulties achieving blood glucose control. 2
• The incidence has decreased significantly with modified, rapidly absorbed analog insulins (insulin lispro, insulin aspart). 2

Other Local Reactions

• Pain occurs in 47.2% of patients at injection sites. 3
• Bruising affects 41.3% of patients. 3
• Bleeding is reported by 55.5% of patients. 3
• Local allergic reactions (erythema, pruritus, induration) occur but are usually short-lived and resolve spontaneously within a few weeks. 2, 4
• Allergic reactions affect 21.7% of patients in some series. 3
• Wound complications occur in 7.5% of patients. 3

Systemic Complications

Hypoglycemia

• Hypoglycemia is by far the most important complication of exogenous insulin, affecting almost all insulin-treated patients. 4
• Inadvertent intramuscular injection significantly increases the risk of frequent and unexplained hypoglycemia due to unpredictable insulin absorption. 1
• Hypoglycemia unawareness (onset of severe neuroglycopenia without warning symptoms) is increasingly recognized, particularly with excessively tight glycemic control or long diabetes duration. 4

Weight Gain

• Obesity is recognized as an adverse event of insulin therapy. 5

Critical Risk Factors for Complications

Intramuscular Injection Risk

• Risk for intramuscular insulin delivery is increased in younger, leaner individuals when injecting into limbs rather than truncal sites (abdomen and buttocks). 1
• Using longer needles significantly increases intramuscular injection risk—needles ≥8 mm inserted perpendicularly may frequently enter muscle in limbs of males and those with BMI <25 kg/m². 6
• Short 4-mm pen needles are effective and well tolerated compared to longer needles, including in adults with obesity, and minimize intramuscular injection risk. 1, 6

Injection Site Selection Errors

• Injecting into areas with lipohypertrophy, scars, or bony prominences contributes to erratic insulin absorption and increased glycemic variability. 1
• Absorption rates differ significantly between sites: abdomen has the fastest absorption, followed by arms, thighs, and buttocks. 7

Prevention Strategies

Proper Site Rotation

• Systematic rotation within one anatomical area (rather than jumping between different body regions) minimizes day-to-day variability in absorption and prevents lipohypertrophy. 1, 7
• The likelihood of lipoatrophy can be reduced by regular rotation of injection sites. 2
• Injection or infusion site rotation is necessary to avoid lipohypertrophy accumulation. 1

Optimal Injection Technique

• Use 4-mm pen needles inserted at 90 degrees for all adults, regardless of age, sex, ethnicity, or BMI. 1, 7
• No skin pinching is required when using 4-mm needles at 90 degrees for most adults. 1, 7
• Inject into appropriate body areas: abdomen (avoiding 2 inches around navel), thigh (upper third anterior lateral), buttock (posterior lateral upper), or upper arm (middle third posterior). 1, 7
• Avoid areas with lipohypertrophy, scars, bony prominences, inflammation, edema, ulceration, or infection. 1, 8

Regular Monitoring

• Examination of insulin injection sites for lipohypertrophy should occur at every regular visit, or at least annually. 1
• Patients should be taught to self-inspect injection sites regularly and recognize lipohypertrophy as raised, soft areas. 1, 7
• Healthcare professionals should assess injection technique during routine follow-up. 1

Impact on Diabetes Management

• Injection technique errors may lead to undesirable glycemic outcomes, excess pain, or skin complications. 1
• Injection technique educational programs can improve patient satisfaction and reduce insulin requirements, frequency of hypoglycemic events, glucose variability, and risk of lipohypertrophy. 1
• Proper insulin injection technique may lead to more effective therapy use and improved clinical outcomes. 1