What are the potential side effects of insulin glargine and human insulin?

Potential Side Effects of Insulin Glargine and Human Actrapid (Regular Insulin)

Both insulin glargine and human regular insulin share common serious side effects—hypoglycemia being the most critical—but insulin glargine demonstrates a reduced risk of nocturnal hypoglycemia compared to intermediate-acting insulins like NPH. 1

Major Side Effects Common to Both Insulins

Hypoglycemia (Most Important)

• Hypoglycemia is the most significant adverse effect of all insulin therapy, presenting with dizziness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, and hunger 2
• Severe hypoglycemia can lead to extreme drowsiness, confusion, loss of consciousness, and potentially death if untreated 2
• Insulin glargine has demonstrated comparable or lower overall hypoglycemia rates compared to NPH insulin, with notably reduced nocturnal hypoglycemia in multiple studies 1, 3
• Regular insulin (Actrapid) causes hypoglycemia particularly when too much is administered or when meals are delayed, with peak action occurring 3-4 hours after injection 1

Weight Gain

• Both insulin preparations cause weight gain, which is associated with increased morbidity and mortality in patients with type 2 diabetes 1, 2
• Weight gain occurs despite insulin glargine not being associated with increased mortality in long-term studies 1
• This side effect should be discussed proactively with patients as it affects adherence and quality of life 1

Injection Site Reactions

• Lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (lumps) can occur at injection sites with repeated use of the same location 2
• Allergic reactions at injection sites are common with both preparations 2
• Proper site rotation within chosen injection areas (abdomen, thighs, upper arms, buttocks) is essential to minimize these complications 2

Serious Adverse Effects Requiring Immediate Medical Attention

Severe Allergic Reactions (Whole Body)

• Rash over entire body, trouble breathing, fast heartbeat, swelling of face/tongue/throat, and sweating require emergency medical care 2
• These reactions can occur with any insulin preparation 2

Hypokalemia (Low Potassium)

• All insulins, including glargine and regular insulin, can cause dangerous shifts of potassium into cells, leading to hypokalemia 2
• This is particularly concerning in patients on medications affecting potassium levels or those with cardiac conditions 2

Heart Failure (When Combined with TZDs)

• Taking thiazolidinediones (pioglitazone, rosiglitazone) with any insulin can precipitate or worsen heart failure 2
• New or worsening symptoms include shortness of breath, ankle/foot swelling, and sudden weight gain 2
• This applies equally to insulin glargine and regular insulin when used with TZDs 2

Specific Considerations for Insulin Glargine

Reduced Nocturnal Hypoglycemia Risk

• Insulin glargine's peakless, 24-hour action profile results in significantly fewer nocturnal hypoglycemia episodes compared to NPH insulin (39.9% vs 49.2% over one month, P=0.02) 1
• The consistent absorption and lack of peak action time reduces unpredictable hypoglycemia 1, 3

Administration-Specific Issues

• Insulin glargine must never be diluted or mixed with other insulins due to its acidic pH, which would alter its pharmacokinetic properties 2
• It should only be administered subcutaneously, never intravenously in routine clinical practice (though accidental IV administration appears less dangerous than expected) 2, 4
• Must be used only when clear and colorless; any cloudiness or discoloration indicates degradation 2

Specific Considerations for Human Regular Insulin (Actrapid)

Timing-Related Hypoglycemia

• Regular insulin has a peak action at 3-4 hours post-injection, creating a specific window of hypoglycemia risk that requires coordinated meal timing 1
• Delayed meals or increased physical activity during peak action significantly increases hypoglycemia risk 1
• Patients must eat at set intervals to avoid hypoglycemia, reducing flexibility compared to basal insulins 1

Shorter Duration Requiring Multiple Daily Doses

• Duration of action is only 6-8 hours, necessitating multiple daily injections for adequate glycemic control 1
• This increases injection burden and potential for injection site complications 1

Clinical Implications for Side Effect Management

Monitoring Requirements

• Frequent blood glucose monitoring is essential when initiating or adjusting either insulin, with particular attention during peak action times 1, 2
• Patients must be educated to recognize hypoglycemia symptoms and carry rapid-acting carbohydrates (4-8 oz juice or soda) for immediate treatment 1, 2

Patient Education Priorities

• Proper injection technique, site rotation, and consistent timing are critical to minimize complications and optimize safety 1, 2
• Patients should never share syringes or needles due to infection risk 2
• Understanding onset, peak, and duration of their specific insulin preparation prevents timing-related adverse events 1

Cost of Side Effect Management

• The economic burden of hypoglycemia includes glucose monitoring supplies, lost work days, and potential emergency care 1
• Despite insulin glargine's higher acquisition cost, reduced hypoglycemia rates may offset overall treatment costs 1

Common Pitfalls to Avoid

• Never use insulin glargine intravenously or in insulin pumps—it is designed exclusively for subcutaneous administration 2
• Avoid injecting into areas with lipodystrophy, lumps, or skin changes, as absorption becomes unpredictable 2
• Do not assume all insulins have identical side effect profiles—the reduced nocturnal hypoglycemia with glargine is clinically meaningful for patient safety and quality of life 1
• Recognize that intensive insulin therapy increases hypoglycemia risk regardless of preparation, requiring individualized glycemic targets based on patient factors 1