What is the most common adverse effect of insulin (intramuscular/intravenous hormone replacement) therapy?

From the Guidelines

The most common adverse effect of insulin therapy is hypoglycemia (low blood sugar). This occurs when insulin lowers blood glucose levels too much, typically below 70 mg/dL. Symptoms of hypoglycemia include shakiness, sweating, confusion, irritability, dizziness, hunger, and in severe cases, loss of consciousness or seizures. According to the most recent study 1, patients should be instructed to check their blood glucose regularly and always have fast-acting carbohydrates (like glucose tablets, juice, or hard candy) readily available to treat hypoglycemia. The standard treatment is to follow the "15-15 rule": consume 15 grams of carbohydrates, wait 15 minutes, and recheck blood glucose. If still low, repeat until glucose normalizes. For severe hypoglycemia where the patient cannot self-treat, glucagon injection (available as Glucagon Emergency Kit, GlucaGen, Gvoke, or Baqsimi nasal spray) may be necessary, as recommended by the latest guidelines 1.

Some key points to consider when managing insulin therapy and preventing hypoglycemia include:

• Monitoring for signs of overbasalization during insulin therapy, such as significant bedtime-to-morning or postprandial-to-preprandial glucose differential, occurrences of hypoglycemia (aware or unaware), and high glycemic variability 1
• Prescribing glucagon for all individuals requiring intensive insulin therapy or at high risk for hypoglycemia, and educating family, caregivers, school personnel, and others providing support on how to administer it 1
• Routinely assessing all people with diabetes for financial obstacles that could impede their diabetes management, and working collaboratively to support these individuals by implementing strategies to reduce costs and improve access to evidence-based care 1

Hypoglycemia occurs because insulin's glucose-lowering effect can be influenced by many factors including missed meals, increased physical activity, alcohol consumption, or incorrect insulin dosing. Patients should be educated about these risk factors and how to adjust insulin accordingly to prevent this common but potentially dangerous side effect. As noted in previous studies 1, the risk of hypoglycemia can be mitigated with proper insulin therapy management and patient education. However, the most recent study 1 provides the most up-to-date guidance on managing insulin therapy and preventing hypoglycemia.

From the FDA Drug Label

Hypoglycemia: Most common adverse reaction of insulin therapy and may be life-threatening. Adverse events commonly associated with human insulin therapy include the following: ... Hypoglycemia

• Hypoglycemia is the most common adverse effect of insulin therapy, and it may be life-threatening 2 3.
• This adverse effect is directly related to the mechanism of action of insulin, which lowers blood glucose levels.
• It is essential to closely monitor blood glucose levels in patients treated with insulin to prevent and manage hypoglycemia.

From the Research

Adverse Effects of Insulin Therapy

• The most common adverse effect of insulin therapy is hypoglycemia, as stated in multiple studies 4, 5, 6, 7.
• Hypoglycemia is a significant barrier to achieving and maintaining good glycemic control, and it can have severe consequences, including morbidity and mortality 5, 6.
• The risk of hypoglycemia is increased with tight glucose control, and it can be exacerbated by factors such as impaired awareness of hypoglycemia and increasing duration of diabetes 4, 5.

Prevalence and Consequences of Hypoglycemia

• The annual prevalence of severe hypoglycemia is around 30% in people with type 1 diabetes, and it is higher in those with risk factors such as strict glycemic control and impaired awareness of hypoglycemia 5.
• Hypoglycemia can cause significant morbidity, including neurological and cardiovascular complications, and it can also affect quality of life, employment, and daily activities 5, 6, 7.
• Severe hypoglycemia can lead to coma, convulsions, and even death, making it a critical concern for individuals with diabetes 5, 6.

Strategies for Reducing Hypoglycemia Risk

• Frequent monitoring of blood sugars, prompt treatment of hypoglycemia, and balancing basal and meal insulin therapy can help reduce the risk of hypoglycemia 4, 7.
• The use of insulin analogues, such as insulin degludec and insulin aspart, can also help minimize the risk of hypoglycemia while maintaining good glycemic control 8.
• A pattern therapy approach and the use of continuous glucose monitoring (CGM) can also be effective in reducing hypoglycemia risk and improving glycemic control 4, 7.