What is the role of basal and bolus insulin (Regular Insulin) in diabetes management?

From the Guidelines

Basal and bolus insulin therapy should be initiated with a basal insulin dose of 0.1-0.2 units/kg/day, with individualized titration over days to weeks as needed, to effectively manage blood glucose levels and minimize the risk of hypoglycemia. This approach is supported by the American Diabetes Association's 2022 standards of medical care in diabetes, which recommend basal insulin as the most convenient initial insulin regimen, added to metformin and other oral agents 1. The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals.

Some key points to consider when implementing basal and bolus insulin therapy include:

• Starting doses can be estimated based on body weight and the degree of hyperglycemia
• Control of fasting glucose can be achieved with human NPH insulin or a long-acting insulin analog
• Long-acting basal analogs (U-100 glargine or detemir) have been demonstrated to reduce the risk of symptomatic and nocturnal hypoglycemia compared with NPH insulin 1
• Clinicians should be aware of the potential for overbasalization with insulin therapy, which can be indicated by a basal dose greater than 0.5 units/kg, high bedtime-morning or post-preprandial glucose differential, hypoglycemia, and high variability 1

In terms of bolus insulin, it is typically taken before meals to cover carbohydrate intake and correct high blood glucose, usually dosed at 1 unit per 10-15g of carbohydrates consumed. Effective management of basal and bolus insulin therapy requires regular blood glucose monitoring, ideally before meals and at bedtime, as well as carbohydrate counting for accurate bolus dosing. Hypoglycemia is a main risk, so patients should always carry fast-acting glucose and know how to recognize and treat low blood sugar (below 70 mg/dL).

From the FDA Drug Label

The safety and efficacy of once daily Insulin Glargine administered either at pre-breakfast, pre-dinner, or at bedtime were evaluated in a randomized, controlled clinical study in adult patients with type 1 diabetes (Study H, n=378) In a randomized, controlled clinical study (Study D), pediatric patients (age range 6 to 15 years) with type 1 diabetes (n=349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. Insulin Glargine was administered once daily at bedtime and NPH insulin was administered once or twice daily. Two 24-week, open-label, active-controlled studies were conducted to compare the safety and efficacy of insulin aspart to regular human insulin injection in adult patients with type 1 diabetes Insulin aspart was administered by subcutaneous injection immediately prior to meals and regular human insulin was administered by subcutaneous injection 30 minutes before meals. NPH insulin was administered as the basal insulin in either single or divided daily doses.

Basal and Bolus Insulin:

• Basal Insulin: Insulin Glargine was administered once daily at bedtime and NPH insulin was administered once or twice daily.
• Bolus Insulin: Regular human insulin was used before each meal, and insulin aspart was administered by subcutaneous injection immediately prior to meals. The studies 2 and 3 show that basal-bolus insulin regimens can be effective in managing type 1 and type 2 diabetes.

From the Research

Basal Insulin

• Basal insulin is usually initiated at a conservative dose of 10 units/day or 0.1-0.2 units/kg/day, then titrated thereafter over several weeks or months, based on patients' self-measured fasting plasma glucose, to achieve an individualized target (usually 80-130 mg/dL) 4.
• The dose of basal insulin should be increased as required up to approximately 0.5-1.0 units/kg/day in some cases 4.
• Newer, long-acting basal insulins provide greater stability and flexibility than older preparations and improved delivery systems 4.

Bolus Insulin

• Bolus insulin is commonly prescribed with basal insulin to limit mealtime glucose excursions (a basal-bolus regimen) 5.
• The rapid-acting insulin analogues (insulin aspart, insulin lispro and insulin glulisine) all have similar pharmacokinetic and pharmacodynamic characteristics and clinical efficacy/safety profiles 5.
• Insulin degludec is an ultra-long-acting insulin analogue with a flat and stable glucose-lowering profile, a duration of action exceeding 30 h and less inter-patient variation in glucose-lowering effect than insulin glargine 5.

Basal-Bolus Regimen

• The basal-bolus regimen is the most effective option for reducing hyperglycemia in patients with type 2 diabetes 6.
• This regimen involves the addition of basal insulin and prandial insulin to achieve or maintain individual glycemic targets over time 6.
• A basal plus strategy has been developed, which considers the addition of increasing injections of prandial insulin, beginning with the meal that has the major impact on postprandial glucose values 6.
• Inpatient treatment with premixed human insulin resulted in similar glycemic control but in significantly higher frequency of hypoglycemia compared with treatment with basal-bolus insulin regimen in hospitalized patients with diabetes 7.

Comparison of Insulin Regimens

• Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycaemic control while lowering the risk of nocturnal hypoglycaemia 8.
• The rate of nocturnal confirmed hypoglycaemia was 25% lower with degludec than with glargine 8.
• Overall serious adverse event rates were similar for the insulin degludec and insulin glargine groups 8.