INSULIN GLARGINE IN TYPE 2 DIABETES

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by relative insulin deficiency, decreased peripheral and hepatic sensitivity to insulin and raised plasma glucose levels¹. T2DM treatment begins with lifestyle interventions, before progressing to pharmacological interventions with advancing disease. Despite the introduction of numerous anti-hyperglycemic medications, many patients with T2DM require insulin, and basal insulin continues to be frequently used either as first-line insulin treatment or as part of multiple daily injection regimens ². Oral hypoglycemic agents are effective agents for diabetes management, although secondary drug failure rates of 5-10% are bothersome. The disappointing results with monotherapy especially the worsening metabolic control is often seen within five years after the initiation of an oral hypoglycemic agent, with more than 50% patients requiring shifting to the insulin-based regimen to achieve optimal glycaemic control³. Basal insulin therapy is recommended if lifestyle modifications and oral antidiabetic agents fail to maintain HbA1c levels <7.5% and has been shown to improve glycemic control⁴. This highlights the fact that adequate basal insulin levels are an essential component of diabetes management. The ideal basal insulin should provide a sustained level of insulin, mimicking physiological basal insulin secretion, reproduce physiological basal insulin secretion, thereby restoring glycemic control, without hypoglycemia¹. Such therapy should have relatively flat/constant insulin concentration profile over time, no pronounced peak, duration of action of at least 24 h, low within-patient variability in fasting plasma glucose (FPG), a favorable safety profile, including low risk of hypoglycemia and weight gain, and be easy to administer and titrate². However, traditional insulin does not fully accomplish this goal. This stimulated the search for insulins with a more prolonged duration of action that could better replicate the physiological basal insulin secretory response⁵. This eventually led to the development of basal insulin-like, Neutral (porcine) protamine Hagedorn (NPH) insulin, Lente insulin, insulin detemir, etc. Still, all these variants are also not able to achieve the desired therapeutic insulin levels. For instance, NPH insulin, intermediate-acting insulin, has a duration of action that is considerably less than 24 h and an activity profile that peaks 3–5 h after administration. NPH insulin administered at bedtime results in high insulin levels when insulin requirements are low. This activity profile is not ideal as it increases the risk of nocturnal hypoglycaemia¹.