Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits
ABSTRACT We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.
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ABSTRACT: Insulin therapy may eventually be required to maintain glycemic control in many patients with type 2 diabetes mellitus. Premixed insulin analogues offer relatively physiologic and predictable time-action profiles and are available in more convenient delivery systems with finer needles than in the past. They also increase the convenience of administration with respect to mealtimes compared with premixed human insulin, and reduce the number of injections compared with basal-bolus therapy. This manuscript describes the development of premixed insulin analogues, reviews efficacy and safety data from randomized trials of premixed insulin analogues compared with human insulin 70/30 or basal insulins, and discusses their use for the management of type 2 diabetes. English-language randomized clinical trials comparing premixed insulin analogues with either premixed human insulin formulations or basal insulins for the treatment of type 2 diabetes, published through May 2005, were identified using PubMed. Pharmacokinetic and pharmacodynamic studies were also included. Abstracts presented at the meetings of the American Diabetes Association, International Diabetes Federation, and the European Association for the Study of Diabetes in 2003 and 2004 were also reviewed. Premixed insulin analogues allow delivery of both basal and prandial insulin in 1 injection and are more convenient than premixed human insulin formulations. The rapid-acting component is absorbed and cleared more quickly, thereby allowing mealtime administration and providing better postprandial glycemic control. Although there is an increased risk of minor hypoglycemia, 3 comparative, randomized trials have shown that patients using premixed analogues twice daily are more likely to reach glycosylated hemoglobin (HbA(1c)) goals compared with those using only insulin glargine once daily. Premixed insulin analogues are available in vials, pens, and dosers. Premixed insulin analogues have a more physiologic time-action profile, can be administered closer to mealtime, and produce greater reductions in the magnitude of postprandial glucose excursions than human insulin 70/30. Despite these advantages, no consistent differences in HbA(1c) reduction or the incidence of hypoglycemia versus human insulin 70/30 have been found in most short-term trials. Although there is an increased risk of minor hypoglycemia, patients using premixed insulin analogues twice daily are more likely to reach HbA(1c) goals than those using only insulin glargine once daily. Further studies are necessary to examine whether these advantages improve patient outcomes in clinical practice.Clinical Therapeutics 09/2005; 27(8):1113-25. DOI:10.1016/j.clinthera.2005.07.003 · 2.59 Impact Factor
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ABSTRACT: Premixed insulin analogues, consisting of rapid-acting and intermediate-acting insulin analogues, were developed to more closely mimic physiological endogenous insulin secretion and meet the needs of patients who require both basal and prandial insulin but wish to limit the number of daily injections. There is considerable variability in onset and duration of action, as well as peak insulin levels, obtained with human insulin formulations such as premixed human insulin 70/30. To overcome these limitations, premixed insulin analogues were developed. Peak insulin levels are twice as high and reached in half the time with the rapid-acting insulin component of a premixed insulin analogue. In the US, two premixed insulin analogue formulations are currently available: insulin lispro 75/25 (75% insulin lispro protamine suspension and 25% insulin lispro) and biphasic insulin aspart 70/30 (BIAsp 70/30; 70% insulin aspart protamine suspension and 30% insulin aspart). They are generally administered twice daily, just before breakfast and dinner. Data from various randomised trials show that both insulin lispro 75/25 and BIAsp 70/30 provide more effective postprandial control of blood glucose than premixed human insulin 70/30 or human insulin isophane suspension (NPH insulin). Longer-term glycaemic control, evaluated as changes in glycosylated haemoglobin, is comparable for premixed insulin analogues and premixed human insulin 70/30 in most studies. Three comparative, randomised trials have shown that patients with type 2 diabetes mellitus using premixed insulin analogues twice daily are more likely to reach glycaemic goals than those using only insulin glargine once daily. Some patients can also reach glycaemic goals with once-daily administration of a premixed insulin analogue. Although the incidence of hypoglycaemia is low, direct comparison across trials of premixed insulin analogues is difficult because of inconsistencies in reporting. Within trials, the incidence of both major (rare) and minor hypoglycaemic episodes during treatment with premixed insulin analogues is low and comparable with rates found with human insulin 70/30. Premixed insulin analogues can be safely used, and are effective and convenient for achieving overall glycaemic control in patients with diabetes. In addition, given the convenience of mealtime dose administration, compliance with insulin therapy may increase with premixed insulin analogues.Drugs 02/2006; 66(1):31-49. DOI:10.2165/00003495-200666010-00003 · 4.13 Impact Factor
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ABSTRACT: The aim of this study was to test the ability of human insulin 70/30, insulin lispro mixture 75/25 (75% neutral protamine lispro [NPL], 25% insulin lispro), and insulin lispro mixture 50/50 (50% NPL, 50% insulin lispro) to control postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus (DM). This single-center, randomized, double-blind, 3-way crossover study was conducted at the Diabetes and Glandular Disease Research Center, San Antonio, Texas. We measured serum glucose responses after a standardized breakfast test meal (500 kcal; 50% carbohydrate, 34% fat, 16% protein) in patients with type 2 DM receiving a single preprandial dose of human insulin 70/30, insulin lispro 75/25, or insulin lispro 50/50 by SC injection. All patients previously used insulin for at least 1 month prior to the study. The glucose responses were compared with those of healthy, untreated subjects administered the identical meal. A total of 33 patients were enrolled (23 with type 2 DM and 10 healthy controls). The baseline characteristics of the patients were as follows: sex ratio (M:F), 17:6; mean (SD) age, 61.3 (10.0) years; mean (SD) body weight, 98.5 (13.2) kg; mean (SD) body mass index, 33.0 (3.8) kg/m(2); mean (SD) glycosylated hemoglobin, 8.1% (1.6%); mean (SD) fasting serum glucose (FSG), 158.7 (27.6) mg/dL; and 56.5% white, 8.7% black, and 34.8% Hispanic. The mean (SD) doses (U/d) of the fixed-mixture preparations were similar: human insulin 70/30, 44.1 (18.2); insulin lispro 75/25, 44.1 (18.2); and insulin lispro 50/50, 43.8 (17.8). FSG levels obtained before the test meal were not significantly different between treatments. Compared with those in healthy subjects, incremental glucose AUC values for the 4 hours after the meal (AUCglucose 0-4) for patients with type 2 DM were 6.4-fold higher with human insulin 70/30, 4.6-fold higher with insulin lispro 75/25, and 3.0-fold higher with insulin lispro 50/50. Each insulin regimen produced AUC(glucose) 0-4 and 2-hour PPG values significantly different from all other regimens (all, P < 0.05). Mean (SD) 2-hour PPG values (mg/dL) were lower with mixtures containing insulin lispro than with human insulin 70/30 and decreased as the proportion of insulin lispro within the fixed mixtures increased: human insulin 70/30, 212.6 (47.0); insulin lispro 75/25, 198.0 (67.5); and insulin lispro 50/50, 158.8 (52.3). In this small study in patients with type 2 DM and healthy controls, preprandial administration of a fixed mixture containing rapid-acting or regular insulin and intermediate-acting components was associated with attenuation of the rise in PPG in patients with type 2 DM administered a test meal. Mixtures containing insulin lispro were associated with greater decreases in PPG concentrations compared with human insulin 70/30. Furthermore, greater amounts of rapid-acting insulin contained within the mixture were associated with better PPG control.Clinical Therapeutics 10/2006; 28(10):1649-57. DOI:10.1016/j.clinthera.2006.10.017 · 2.59 Impact Factor