Nateglinide is used as monotherapy as an adjunct to diet and exercise for the management of type 2 diabetes mellitus in patients whose hyperglycemia cannot be controlled by diet and exercise alone and who have not been chronically treated with other oral antidiabetic agents. Nateglinide also may be used in combination with metformin as an adjunct to diet and exercise for the management of type 2 diabetes mellitus in patients who do not achieve adequate glycemic control with metformin or a thiazolidinedione alone. However, in such patients, nateglinide should be added to, not substituted for, these drugs. In addition, the manufacturer states that nateglinide should not be added to or substituted for other insulin secretagogues (e.g., sulfonylureas) in patients whose hyperglycemia cannot be controlled adequately with such drugs.
The American Diabetes Association (ADA) currently classifies diabetes mellitus as type 1 (immune mediated or idiopathic), type 2 (predominantly insulin resistance with relative insulin deficiency to predominantly an insulin secretory defect with insulin resistance), gestational diabetes mellitus, or that associated with certain conditions or syndromes (e.g., drug- or chemical-induced, hormonal, that associated with pancreatic disease, infections, specific genetic defects or syndromes). Type 1 diabetes mellitus was previously described as juvenile-onset (JOD) diabetes mellitus, since it usually occurs during youth. Type 2 diabetes mellitus previously was described as adult-onset (AODM) diabetes mellitus. However, type 1 or type 2 diabetes mellitus can occur at any age, and the current classification is based on pathogenesis (e.g., autoimmune destruction of pancreatic β cells, insulin resistance) and clinical presentation rather than on age of onset. Many patients' diabetes mellitus does not easily fit into a single classification. Epidemiologic data indicate that the incidence of type 2 diabetes mellitus is increasing in children and adolescents such that 8-45% of children with newly diagnosed diabetes have nonimmune-mediated diabetes mellitus; most of these individuals have type 2 diabetes mellitus, although other types, including idiopathic or nonimmune-mediated type 1 diabetes mellitus, also have been reported.
Patients with type 2 diabetes mellitus have insulin resistance and usually have relative (rather than absolute) insulin deficiency. Most patients with type 2 diabetes mellitus (about 80-90%) are overweight or obese; obesity itself also contributes to the insulin resistance and glucose intolerance observed in these patients. Patients with type 2 diabetes mellitus who are not obese may have an increased percentage of abdominal fat, which is an indicator of increased cardiometabolic risk. While children with immune-mediated type 1 diabetes generally are not overweight, the incidence of obesity in children with this form of diabetes is increasing with the increasing incidence of obesity in the US population. Distinguishing between type 1 and type 2 diabetes mellitus in children may be difficult since obesity may occur with either type of diabetes mellitus, and autoantigens and ketosis may be present in a substantial number of children with features of type 2 diabetes mellitus (e.g., obesity, acanthosis nigricans).
Metformin generally is recommended as initial antidiabetic therapy in patients with type 2 diabetes mellitus, provided no contraindications exist, because of the absence of weight gain or hypoglycemia, generally low adverse effect profile, and relatively low cost of this drug. Some experts state that meglitinides may be appropriate choices in selected patients but are not preferred as second-line therapy after failure of metformin monotherapy because of their overall lower effectiveness, limited clinical data, and relative expense. In addition, use of meglitinides are not recommended in hospitalized patients with diabetes mellitus because of a lack of data in such patients.
Safety and efficacy of nateglinide as monotherapy for the management of type 2 diabetes mellitus were established in several randomized, double-blind studies of up to 24 weeks' duration. Nateglinide improved glycemic control as measured by fasting glucose and glycosylated hemoglobin (Hb A1c) compared with placebo. In clinical studies, nateglinide generally was less effective in patients who previously were treated with other oral antidiabetic agents compared with treatment-naive patients.
Efficacy of nateglinide in combination with metformin was established in several studies of 24 weeks' duration in which combined therapy resulted in improved glycemic control compared with monotherapy with nateglinide or metformin. However, in a 12-week study in patients with type 2 diabetes mellitus inadequately controlled by glyburide monotherapy, the addition of nateglinide did not produce any improvement in glycemic control when compared with glyburide monotherapy.
Efficacy of nateglinide in combination with rosiglitazone was established in a study of 24 weeks' duration in patients inadequately controlled with rosiglitazone monotherapy. The addition of nateglinide (120 mg 3 times daily) to rosiglitazone monotherapy (8 mg once daily) resulted in improved glycemic control (as determined by reduction of HbA1c from baseline, the primary clinical end point) compared with continuation of rosiglitazone monotherapy. The mean change in body weight from baseline was greater in patients receiving combination therapy than in those continuing to receive monotherapy.
For additional information on the management of type 2 diabetes mellitus, see Uses: Diabetes Mellitus in Repaglinide 68:20.16.