What is the mechanism of action of Insulin Glargine (insulin glargine)?

From the Guidelines

Glargine is a long-acting insulin analog that should be used to manage diabetes mellitus, with a standard starting dose of 10 units once daily for adults with type 2 diabetes, and 0.2-0.4 units per kilogram of body weight for those with type 1 diabetes, as it provides a steady, basal level of insulin for approximately 24 hours with minimal peaks in action, and helps maintain blood glucose control between meals and overnight, as supported by the most recent study 1.

Key Points

• Glargine is typically administered once daily, and should be injected subcutaneously in the abdomen, thigh, or upper arm, with rotation of injection sites to prevent lipohypertrophy.
• The long duration of action of glargine results from its unique formulation that forms microprecipitates after injection, allowing for slow, consistent absorption.
• Common side effects of glargine include hypoglycemia, injection site reactions, and weight gain.
• Blood glucose monitoring is essential when using glargine to ensure proper dosing and avoid complications.

Administration and Dosage

• Glargine should not be mixed with other insulins in the same syringe.
• The starting dose of glargine can be estimated based on body weight and the degree of hyperglycemia, with individualized titration over days to weeks as needed, as recommended by the American Diabetes Association 1.

Benefits and Risks

• Glargine has been demonstrated to reduce the risk of symptomatic and nocturnal hypoglycemia compared with NPH insulin, although these advantages are modest and may not persist, as shown in clinical trials 1.
• Longer-acting basal analogs, such as U-300 glargine or degludec, may convey a lower hypoglycemia risk compared with U-100 glargine when used in combination with oral agents, as supported by recent studies 1.

From the FDA Drug Label

The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. The median time between subcutaneous injection and the end of pharmacological effect was 14.5 hours (range: 9. 5 to 19.3 hours) for NPH insulin, and 24 hours (range: 10. 8 to >24 hours) (24 hours was the end of the observation period) for Insulin Glargine.

Insulin Glargine is a long-acting human insulin analog.

• The duration of action of Insulin Glargine is approximately 24 hours.
• The mechanism of action is the regulation of glucose metabolism by stimulating peripheral glucose uptake and inhibiting hepatic glucose production.
• Key points about Insulin Glargine include its slower and more prolonged absorption compared to NPH insulin, with a relatively constant concentration/time profile over 24 hours and no pronounced peak 2.

From the Research

Properties and Mechanism of Insulin Glargine

• Insulin glargine is a recombinant human insulin analogue produced by DNA technology using a nonpathogenic strain of Escherichia coli 3.
• It has a stable molecule which is soluble in slightly acidic conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue, resulting in a delayed absorption and a fairly constant, basal insulin supply without peaks in plasma insulin levels for approximately 24 hours 3.
• Insulin glargine differs in structure from native human insulin by 3 amino acids, a structural modification that provides a delayed onset of action and a constant, peakless effect that has a duration of at least 24 hours 4.

Efficacy and Tolerability of Insulin Glargine

• Insulin glargine is indicated as a once daily subcutaneous injection to provide basal glycaemic control in adults and children aged >6 years with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus 3.
• Clinical trials have demonstrated that insulin glargine produces statistically significant reductions in FPG or FBG levels at end point both compared with baseline and compared with NPH insulin 4.
• Insulin glargine has been shown to have equal clinical efficacy to NPH insulin, produces similar reductions in HbA(1c), and is associated with lower FPG and FBG levels and a consistent and significant reduction in the incidence of nocturnal hypoglycemia in patients with type 2 diabetes 4, 5.
• The most common adverse events with insulin glargine treatment were injection site pain, which was mild and did not require treatment discontinuation 3.

Comparison with NPH Insulin

• Insulin glargine has been compared with NPH insulin in several clinical trials, with results showing that insulin glargine has a lower incidence of hypoglycaemia, especially nocturnal hypoglycaemia, compared with NPH insulin 3, 4, 5.
• Insulin glargine has been shown to provide a more stable and consistent basal insulin supply compared with NPH insulin, with a reduced risk of nocturnal hypoglycaemia 3, 4, 5.

Use in Type 2 Diabetes

• Insulin glargine is used as a basal insulin replacement in patients with type 2 diabetes, with the goal of achieving good glycaemic control with aggressive titration of the insulin dose 5, 6.
• Insulin glargine has been shown to be effective in reducing HbA1c levels and improving fasting plasma glucose levels in patients with type 2 diabetes, with a reduced risk of nocturnal hypoglycaemia compared with NPH insulin 5, 7.