Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin

OBJECTIVE: To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone. RESEARCH DESIGN AND METHODS: A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily in = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose <6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg. RESULTS: The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis. The mean change (means +/- SD) in HbA1c from baseline to end point was similar in the insulin glargine group (-0.41 +/- 0.1%) and the NPH group (-0.59 +/- 0.1%) after patients began with an average baseline HbA1c of approximately 8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.%) However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase(26.5 vs. 35.5%, P = 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P < 0.0007). CONCLUSIONS: In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin.     

Efficacy and safety of HOE 901 versus NPH insulin in patients with type 1 diabetes. The European Study Group of HOE 901 in type 1 diabetes

OBJECTIVE: HOE 901 (Hoechst Marion Roussel, Frankfurt, Germany) is a biosynthetic insulin with a prolonged action. The aim of this study was to compare the effect of the long-acting insulin analog HOE 901 with NPH insulin regarding glycemic control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 333 type 1 diabetic patients were enrolled in this multinational parallel group trial. Subjects were randomized either to two different formulations of HOE 901 (the formulations differed only in zinc content) or to NPH insulin. The study was only partially blinded because patients can distinguish HOE 901 (a clear solution) from NPH (a cloudy suspension). In addition to premeal injections of regular insulin, patients received HOE 901 at bedtime or NPH once daily at bedtime or twice daily in the morning and at bedtime. RESULTS: Fasting plasma glucose levels were significantly lower with HOE 901 (-1.88 mmol/l. P = 0.0005) as were fasting self-monitored blood glucose levels (-0.80 mmol/l, P = 0.0020). HbA1c levels also showed a significant reduction with HOE 901 (-0.14%) versus NPH (P = 0.030). The overall frequency of hypoglycemia did not differ, but the frequency of nocturnal hypoglycemia was significantly (P = 0.0037) lower with HOE 901 (36 vs. 55%). However, this effect on nocturnal hypoglycemia was significant only versus NPH once daily not NPH twice daily. The pattern of adverse events and injection site reactions with HOE 901 was similar to that with NPH. CONCLUSIONS: This study indicates that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks, and HOE 901 has a possible safety benefit in terms of nocturnal hypoglycemia.     

Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group

OBJECTIVE: Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion. It recently received approval from the Food and Drug Administration. The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 4-week trial, 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80 microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously once daily at bedtime. NPH insulin was given either once daily (at bedtime) or twice daily (before breakfast and at bedtime), according to the patient's prestudy regimen. The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose. RESULTS: At study end point, insulin glargine-pooled groups had significantly lower fasting plasma glucose (FPG) levels than the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P = 0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily. FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin. A subset of patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8 mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both formulations of insulin glargine were well tolerated, similar to NPH insulin. CONCLUSIONS: Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.     

Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy

OBJECTIVE: To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) < or =6.0 mmol/l. RESULTS: Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA(1c) (Diabetes Control and Complications Trial-aligned assay, normal range 4.6-6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 +/- 0.4 kg (means +/- SE) (P = 0.01) versus 2.7 +/- 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 +/- 0.8 to 34.1 +/- 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 +/- 0.9 to 29.1 +/- 1.3 (P < 0.002) with insulin/repaglinide. CONCLUSIONS: Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.     

Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes

OBJECTIVE: Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: All studies were 24-28 weeks long, except one 52-week study, for which interim 20-week data were used. RESULTS: Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA(1c) (< or =7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively. CONCLUSIONS: These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA(1c) target of < or =7.0% in patients with type 2 diabetes.     

Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes

OBJECTIVE: Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin. RESEARCH DESIGN AND METHODS: This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l. RESULTS: A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P > 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level <2.0 mmol/l compared with subjects receiving NPH insulin. CONCLUSIONS: Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes.     

A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes

OBJECTIVE: To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime. RESULTS: Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (< 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034). CONCLUSIONS: Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.     

Outcomes with insulin glargine in patients with type 2 diabetes previously on NPH insulin: evidence from clinical practice in Spain

Aim: We evaluated the effectiveness of insulin glargine (glargine)‐based regimens in patients with type 2 diabetes mellitus (T2DM) in clinical practice in Spain. Methods: This was a retrospective, registry‐based study of 1482 patients treated with neutral protamine Hagedorn (NPH) who were either switched to glargine or maintained on NPH at investigators’ discretion. The primary outcomes were HbA_1c change over a period of 4–9 months follow‐up and incidence of hypoglycaemia. Results: Prior to switching treatment, mean ± standard deviation HbA_1c was worse in the glargine vs. the NPH group (8.3 ± 1.2% vs. 7.9 ± 1.1% respectively; p < 0.0001). After 4–9 months of treatment, mean reductions in HbA_1c were greater with glargine vs. NPH (?1.0 ± 1.0% vs. ?0.2 ± 0.8% respectively; p < 0.0001) and the incidence of hypoglycaemia in the month prior to the study visit was lower (21.8% vs. 47.6% respectively; p < 0.0001). An expected reduction in dosing frequency, as well as in the basal insulin dose was reported for glargine vs. NPH, with 97.3% of glargine‐treated patients on once‐daily injections and 81.2% on NPH receiving twice‐daily therapy. Improvements in treatment satisfaction were significantly higher with glargine (p < 0.0001). Conclusions: In a Spanish clinical practice setting, patients with T2DM who switched to glargine from NPH experienced significantly greater reductions in mean HbA_1c and a lower incidence of hypoglycaemia than patients maintained on NPH.     

Risk for nocturnal hypoglycemia with biphasic insulin aspart 30 compared with biphasic human insulin 30 in adults with type 2 diabetes mellitus: A meta-analysis

Background: Insulin is recommended as a second-line treatment after diet and metformin fail to reach and/or maintain glycemic targets considered to minimize the risk for long-term diabetic complications. Hypoglycemia and the fear of developing hypoglyce-mia, however, remain substantial barriers to the initiation and optimal use of insulin.Objective: The aim of this study was to compare biphasic insulin aspart 30 (BIAsp 30) with biphasic human insulin 30 (BHI 30) with respect to glycemic control and the risk for hypoglycemia using a meta-analysis of clinical trials comparing these insulins in patients with type 2 diabetes mellitus (T2DM).Methods: We included all published and unpublished, randomized, controlled trials in adult patients with T2DM (treatment duration ≥12 weeks) for which individual patient data were available. All clinical databases and local trial registries of Novo Nordisk A/S (Soeborg, Denmark) were searched to identify clinical trials comparing the 2 products. The predefined primary end point of the study was the overall rate of nocturnal hypoglyce-mia (major, minor, and symptoms-only hypoglycemia occurring from 12:00–6:00 AM). Hypoglycemia was analyzed using a negative binomial distribution model, accounting for exposure time. Glycemic end points were analyzed at 12 to 16 weeks of treatment using ANCOVA, adjusting for baseline. Secondary safety end points were the rates of major hypoglycemia (hypoglycemia requiring third-party assistance), minor hypoglycemia (symptoms confirmed by plasma glucose [PG] <3.1 mmol/L), daytime hypoglycemia (major, minor, and symptoms-only hypoglycemia occurring from 6:01 AM–11:59 PM), overall hypoglycemia (the sum of all major, minor, and symptoms-only episodes), and change in weight from baseline to 12 to 16 weeks of treatment. Secondary efficacy end points were changes in glycosylated hemoglobin (HbA_1c), fasting PG (FPG), postprandial PG increment (averaged over breakfast, lunch, and dinner), and insulin dose.Results: Nine randomized, parallel or crossover trials were included (N = 1674; male sex, 57%; mean [SD] age, 61.0 [10.6] years; body mass index, 26.7 [4.6] kg/m²; HbA_1c, 8.1% [1.4%]; duration of diabetes, 10.9 [7.9] years). Rates of overall hypoglycemia were not significantly different (rate ratio [RR] = 1.08; 95% CI, 0.94–1.24; P = NS) between treatments. BIAsp 30 had a 50% lower rate of nocturnal hypoglycemia than BHI 30 (RR = 0.50; 95% CI, 0.38–0.67; P < 0.01), whereas the rate of daytime hypoglycemia was 24% lower for BHI 30 (RR = 1.24; 95% CI, 1.08–1.43; P < 0.01). The likelihood of major hypo-glycemia was significantly lower with BIAsp 30 compared with BHI 30 (odds ratio = 0.45; 95% CI, 0.22–0.93; P < 0.05). BIAsp 30 was associated with reduced PPG increment (averaged over breakfast, lunch and dinner) compared with BHI 30 (treatment difference, ?0.31; 95% CI, ?0.49 to ?0.07; P < 0.01). There was a significantly larger reduction in FPG associated with BHI 30 (treatment difference, 0.63; 95% CI, 0.31–0.95; P < 0.01). However, no significant treatment difference was found for HbA_1c (treatment difference, 0.04; 95% CI, ?0.02 to 0.10; P = NS).Conclusion: This meta-analysis found BIAsp 30 to be associated with a significantly lower rate of nocturnal and major hypoglycemia, but a significantly increased risk for daytime hypoglycemia, compared with BHI 30 at a similar level of HbA_1c in patients with T2DM.     

非初诊2型糖尿病患者胰岛素泵强化治疗后血糖达标的影响因素

目的观察非初诊2型糖尿病患者经短期胰岛素泵强化治疗后3个月的血糖情况,并分析影响血糖达标的因素。方法将符合纳入标准的190例2型糖尿病患者随机分为观察组和对照组,观察组使用胰岛素泵强化治疗14 d后改为预混胰岛素治疗,对照组采用预混胰岛素治疗,随访治疗3个月,比较两组治疗前后的血糖、糖化血红蛋白(Hb A1c)、空腹C肽(FCP)等指标的变化,并分析影响治疗后血糖达标的基线因素。结果 (1)与对照组相比,观察组治疗后的空腹血糖(FPG)、餐后2 h血糖、Hb A1c显著下降,FCP显著上升,差异有统计学意义(P<0.01)。与治疗前相比,观察组治疗后的FPG、餐后2 h血糖、Hb A1c明显降低,FCP升高,差异有统计学意义(P<0.01)。(2)观察组治疗后的血糖达标率(Hb A1c<7.0%)为35.6%,而对照组血糖的达标率仅为26.2%。比较观察组和对照组中血糖达标(Hb A1c<7.0%)与不达标(Hb A1c≥7.0%)患者的基线特点,两者在病程、FPG、餐后2 h血糖、Hb A1c、FCP上均有统计学差异(P<0.05),在性别、年龄、体质量指数(BMI)上无统计学差异(P>0.05)。(3)Logistic回归分析结果显示影响观察组血糖达标的主要基线因素包括:Hb A1c、FCP,OR值分别为1.24、0.27。结论对非初诊2型糖尿病患者进行短期胰岛素泵强化治疗可提高3个月后血糖达标率,效果显著优于对照组。Hb A1c、FCP是影响血糖达标的主要基线因素。     

Insulin glargine in combination with oral antidiabetic drugs as a cost-equivalent alternative to conventional insulin therapy in type 2 diabetes mellitus

BACKGROUND AND RATIONALE: Recent data suggest that insulin glargine might be a cost-effective alternative to conventional insulin therapy in patients with type 2 diabetes mellitus (T2DM). The aim of this observational study was to evaluate the treatment costs of insulin glargine in combination with oral antidiabetic drugs (OADs) compared with conventional insulin therapy in T2DM in everyday clinical practice. PATIENTS AND METHODS: Data were obtained from a cohort of 678 patients with T2DM not adequately controlled by OADs alone (HbA1c mean 9.1 +/- 1.7%). Patients received either insulin glargine in addition to oral therapy or were switched to conventional insulin therapy. Treatment and dosing decisions were made at the physician's discretion, reflecting everyday practice. Patients were followed for 2-4 months. Primary outcome parameters were total treatment costs and clinical efficacy. RESULTS: The two therapeutic regimens were equally effective in decreasing HbA1c to 7.8% (p < 10(-9)). Patients in the insulin glargine plus OAD group controlled their blood glucose level at endpoint with a median of 60 test strips per month and those in the conventional insulin therapy group with a median of 80 strips per month (p = 0.000000739). Total daily costs of insulin, needles, glycemic control and OAD treatment per patient were similar in the two treatment groups (insulin glargine group 1.91 Euro vs conventional group 1.99 Euro). CONCLUSION: The two treatment regimens were equally effective in improving glycemic control. These results were achieved with significantly lower insulin doses and fewer blood glucose test strips in the insulin glargine group, which therefore led to cost equivalence when compared with conventional insulin therapy.     

Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial

OBJECTIVE: Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration. RESEARCH DESIGN AND METHODS: People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet(morn+bed)) or at a 12-h interval (IDet(12h)). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart. RESULTS: With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet(12h) vs. NPH, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet(12h) vs. NPH, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 0.040). CONCLUSIONS: Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs.     

Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group.

The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.