A Direct Efficacy and Safety Comparison of Insulin Aspart, Human Soluble Insulin, and Human Premix Insulin (70/30) in Patients With Type 2 Diabetes

Abstract

OBJECTIVE -Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes, this trial was performed to compare the efficacy and safety of preprandial insulin aspart with human soluble insulin (HI) and human premix (70% NPH/30% regular) insulin (MIX). RESEARCH DESIGN AND METHODS-A total of 231 type 2 diabetic patients were randomized to insulin aspart (n ϭ 75), HI (n ϭ 80), or MIX (n ϭ 76) for 3 months. Insulin aspart and HI were administered with or without bedtime NPH insulin. A total of 204 patients completed the trial according to protocol. HbA 1c , 7-point blood glucose, insulin dosage, and hypoglycemic episodes were recorded. The primary end point was "change of HbA 1c " from baseline to last visit. Analysis for equivalence was performed by t tests with three subtests. T he major therapeutic goals in subjects with type 2 diabetes are to optimize blood glucose control, to reduce overweight, and to normalize lipid disturbances and elevated blood pressure. It has been shown that the intensive management of type 2 diabetes reduces the risk for chronic complications (1). Diet and exercise, aiming at weight reduction, are the cornerstones of therapy. However, pharmacological treatment with oral hypoglycemic agents (OHAs) or insulin is often required (2-13). RESULTSInsulin aspart is a rapid-acting human insulin analog: replacement of proline at position B28 by aspartic acid reduces the tendency for self-association to hexamers and dimers and leads to faster absorption into the blood stream (14). Because of its short-acting profile, insulin aspart is administered immediately before main meals (15,16). Postprandial administration was also demonstrated to be a feasible therapeutic option (17). Several clinical studies showed that insulin aspart is as effective as human soluble insulin (HI) in type 1 diabetic patients (18 -23).There are only limited data for insulin aspart in type 2 diabetes and no comparisons so far among preprandial use of HI, a short-acting insulin analog, and standard human premix insulin (MIX) in a type 2 diabetic population. The aim of the present trial was to compare the efficacy and safety of three different therapeutic regimens in type 2 diabetic patients: 1) preprandial insulin aspart with or without additional NPH insulin once daily at bedtime; 2) preprandial HI with or without additional NPH insulin once daily at bedtime; and 3) MIX (70% NPH/30% regular) once or twice daily.The intensive management of blood glucose reduces the incidence of progression of diabetes complications in type 2 diabetic patients (1,24) but may require multiple-injection regimens for insulin, which is not desirable for all people with type 2 diabetes. Therefore, we wanted to find out whether MIX (70% NPH/30% regular) was as effective as insulin aspart and HI in controlling HbA 1c .RESEARCH DESIGN AND METHODS -The study was approved by 18 ethics committees responsible for the 30 centers participating in the trial, and the study was performed in accordance with the principles ...

Long-term impact of a structured group-based inpatient-education program for intensive insulin therapy in patients with diabetes mellitus

“…In the present study, baseline HbA1c was signifi cantly lower in the patients with type 1 than in study populations in previous studies (Sämann et al: 8.1%,Plank et al: 7.9%), suggesting the greatest benefi t of diabetes education might occur in patients with insuffi cient glycemic control. In contrast to previous studies [13][14][15][16], we observed a long-term benefi t in type 2 diabetic patients only. Worse metabolic control at baseline and/or higher motivation of the patients in our study could explain these discrepant results.…”

Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta-analyses

“…Lower fasting glucose and PPG with basal-bolus therapy were found in one trial, which had significantly greater total insulin daily dose in that arm [55]. Three trials reported similar weight gain in both study arms [54,55,57]. Similar rates of all hypoglycaemic events were reported in three trials [54,55,57] and two trials reported similar rates of severe hypoglycaemia [54,55].…”

“…One trial found greater HbA 1c reduction with prandial (and discretionary basal) insulin compared with once-or twice-daily biphasic insulin [57]. Lower fasting glucose and PPG with basal-bolus therapy were found in one trial, which had significantly greater total insulin daily dose in that arm [55].…”

Safety of basal-bolus versus premixed insulin intensification regimens in the management of type 2 diabetes mellitus: A narrative review of a 14-year experience

“…Our initial search identified 20 papers, 12,21e39 five studies of which were excludes 21,24,32,38,39 because they compared regimens other than the two specific regimens, two were excluded because they involved Type 1 Diabetes Mellitus patients, 22,34 two were excluded because there was no safety related parameter measured in the study 31,35 and one was excluded due to different injection formulations used for the BB regimen arm. 37 The remaining ten selected studies and their characteristics were analysed as shown in Table 1.…”