Dosing of insulin glargine in the treatment of type 2 diabetes

Background: Type 2 diabetes is a progressive disease characterized by insulin resistance and declining P-cell function, often leading to a requirement for insulin therapy to maintain good glycemic control and prevent diabetes-associated complications. Adequate insulin dosing is crucial to the achievement of good glycemic control with minimal hypoglycemia, and dose titration immediately following insulin initiation is needed to ensure its success. Insulin may be initiated as an add-on therapy to oral treatment using a single evening basal insulin dose and titrating according to fasting blood glucose (FBG) levels (with an ideal target of <5.5 mmol/L [<100 mg/dL] to achieve glycosylated hemoglobin [HbA(1c)] <7%). Objective: This review investigated options for, and clinical efficacy of, titration algorithms of insulin glargine in type 2 diabetes. Methods: Articles from peer-reviewed journals were identified through searches of MEDLINE (years: 2000-2006). Search terms included insulin glargine, titration, algorithm, and type 2 diabetes. Studies were assessed and included in this review if they provided information regarding the method of dose titration of insulin glargine used. Results: A total of 12 studies were identified and included in this reviews In the 24-week Treat-to-Target study. in which 756 patients were randomized to receive either insulin glargine or neutral protamine Hagedorn (NPH) insulin, once-daily using a simple titration regimen (titration of daily insulin dose by 0-2, 2, 4, or 6-8 IU if mean fasting plasma glucose over the 3 previous days was >= 5.6-<6.7, >= 6.7-<7.8, >= 7.8-<10.0 or >= 10 mmol/L [>= 100-<120, >= 120-<140, >= 140-<180, or >= 180 mg/dL], respectively, in the absence of plasma glucose <4.0 mmol/L [<72 mg/dL]) more patients reached HbA(1c) <= 7% without nocturnal hypoglycemia with insulin glargine versus NPH insulin (33.2% vs 26.7%; P < 0.05). In the 24-week ATLANTUS (A Trial comparing LANTUS Algorithms to achieve Normal blood glucose Targets in subjects with Uncontrolled blood Sugar) study, 4961 patients were randomized to receive insulin glargine with either clinic-managed (as in the Treat-to-Target study) or patient-managed dose titration (increase insulin dose by 2 IU every 3 days in the absence of blood glucose <4.0 mmol/L [<72 mg/dL]). Greater reductions in HbA(1c) were found with patient- versus clinic-managed titration (-1.22% vs -1.08%; P < 0.001), and fewer patients experienced hypoglycemia with clinic-managed titration (29.8% vs 33.3%; P < 0.01). Conclusions: The results from the studies discussed in this review suggest that adequate titration of the insulin dose, either by physicians or by patients, can help patients reach treatment goals, including HbA(1c) <7% and FBG <5.5 mmol/L (<100 mg/dL). The choice between algorithms may depend on clinical circumstance and a patient's willingness and ability to become more involved in management of therapy.