Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: A multinational, 24-week, randomized, open-label, parallel-group comparison (original) (raw)
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Diabetic Medicine, 2006
Aims To compare insulin lispro mixture (25% insulin lispro and 75% NPL; Mix 25/ 75) twice-daily plus oral glucose-lowering medications (metformin and / or sulphonylurea) with once-daily insulin glargine plus oral agents with respect to postprandial glycaemic control and other glucose and lipid parameters in patients with Type 2 diabetes inadequately controlled with insulin and/or oral glucose-lowering agents. Methods This was a randomized, open-label, crossover study. Prestudy oral agents were continued and patients not already on oral agents were treated with metformin. Mix 25/75 and insulin glargine were adjusted over 3 months to attain premeal plasma glucose (PG) < 6.0 mmol /l and were then given during a 24-h in-patient test meal period with frequent PG, serum triglyceride (TG) and free fatty acid (FFA) measurements. Results Twenty patients (10 F/10 M; mean ± SD age 54.0 ± 10.7 years, body mass index 37.0 ± 8.6 kg /m 2 , HbA 1c 8.4 ± 1.01%) participated. Mean doses were 23 U before the morning and 37 U before the evening meal for Mix 25/75 and 44 U for insulin glargine. The combined 2-h morning and evening meal postprandial plasma glucose (PPG) was not different between groups (9.2 ± 2.04 vs. 9.9 ± 1.66 mmol/l, P = 0.161). Mix 25/75 was associated with a lower mean 2-h PPG for all meals combined (9.0 ± 1.88 vs. 9.9 ± 1.80 mmol /l, P < 0.05) and lower mean 24-h PG (6.7 ± 1.00 vs. 7.5 ± 1.32 mmol /l, P < 0.01). Eight patients experienced mild hypoglycaemia (PG < 3.5 mmol /l) with Mix 25/ 75 and 3 with insulin glargine. The endpoint HbA 1c was lower with Mix 25/75 (6.9 ± 0.52% vs. 7.3 ± 0.81%, P < 0.05). Conclusions In a 24-h test-meal setting in 20 patients, Mix 25/75 insulin plus oral glucose-lowering agents was associated with lower mean PPG and 24-h PG, more mild hypoglycaemia and similar TG, FFA and fasting PG concentrations. HbA 1c was lower with Mix 75/25 plus oral agents, although it may not have reached steady state due to ongoing dose adjustment.
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET …
Diabetologia
Aims/hypothesis: In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA 1c ; secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia. Methods: In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA 1c ≥8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups. Results: During the last 12 weeks, FPGs averaged 5.75± 0.02 and 5.96±0.03 mmol/l (p<0.001) and insulin doses were 68±5 and 70±6 IU/day (0.69±0.05 and 0.66±0.04 IU kg −1 day −1 , NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA 1c was 7.14±0.12 and 7.16±0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1± 0.8 episodes/patient-year) than in the NPH+MET group (9.0±2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1±0.3 mmol/l) than in the G+MET group (8.6±0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA 1c <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7±0.2 vs 6.7± 0.3 mmol/l for patients reaching vs those not reaching target, p<0.01). Conclusions/interpretation: Good glycaemic control can be achieved with both G+MET and NPH+ MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinnertime hyperglycaemia compared with NPH+MET.
Diabetes, Obesity and Metabolism, 2003
Background: The glycaemic control of thrice daily treatment with premixed biphasic insulin aspart (BIAsp) without other antidiabetic therapy was tested in type 2 diabetic patients, in order to compare the glucose control of a 'high' mixture (BIAsp 70) or a 'medium' mixture (BIAsp 50) (70 or 50% soluble IAsp and 30 or 50% protamine-crystallized IAsp, respectively) administered just before dinner. Aim: To compare these regimens to conventional 30 : 70 premixture on a twice a day basis. Methods: This randomized, double-blind, two-period crossover study included 16 patients with type 2 diabetes. Twenty four-hour serum glucose and insulin profiles were obtained thrice: (1) after a one-week run-in period with biphasic human insulin (BHI) 30/70 twice daily (run-in), (2) after 4 weeks of treatment with thrice daily BIAsp 70 before breakfast, lunch and dinner (Dinner70 regimen) and (3) after 4 weeks of BIAsp 70 before breakfast and lunch and BIAsp 50 before dinner (Dinner50). Results: Daytime average serum glucose was lower with Dinner70 compared to run-in (9.6 AE 0.39 mmol/l vs. 11.2 AE 0.61 mmol/l, p < 0.05). Postprandial glucose excursions after breakfast and lunch were lower, but fasting morning glucose was higher during the treatment periods than in the run-in period. Twenty four-hour C-peptide AUC was considerably lower during both treatment periods than in the run-in period (run-in/Dinner50 ratio 1.29 [1.08; 1.54] p < 0.01; run-in/Dinner70 ratio 1.31 [1.08;1.58], p < 0.01). Conclusions: Switching the dinner dose to BIAsp 50 did not alter overall glucose control significantly from that provided with BIAsp 70. Exploratory analyses between the two active treatment regimens and run-in/BHI indicate that thrice daily BIAsp 70 administration: (1) for optimization of the night-time control, the dinner dose needs adjustment or replacement by a premixed insulin with a larger proportion of basal insulin than BIAsp 50 and (2) none of the premixtures adequately provide for both the evening meal and overnight requirements.
Basal insulin or premix analogue therapy in type 2 diabetes patients
European Journal of Internal Medicine, 2007
Background: We sought to compare the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) given twice daily with once-daily insulin glargine in patients with type 2 diabetes beginning insulin therapy and who did not use thiazolidinediones, which are contraindicated with insulin in the European Union, in a subpopulation (N = 157) of the INITIATE study. Methods: At baseline, HbA 1c was ≥ 8.0% on ≥ 1000 mg/day metformin alone or in combination with other oral antidiabetic drugs (OADs; e.g. sulphonylurea or alpha-glucosidase inhibitors). Metformin was adjusted up to 2550 mg/day and other OADs were discontinued. Starting insulin doses were subsequently adjusted weekly for 26 weeks by algorithm-directed titration. Results: The proportion of patients achieving a HbA 1c below 7.0% at 28 weeks was greater with BIAsp 30 than with insulin glargine (65% vs 41%, P = 0.003). The mean reduction in HbA 1c was greater for BIAsp 30 than for insulin glargine: −2.89 ± 1.6% vs −2.46 ± 1.6%, respectively (P = 0.035). Postprandial glucose increments were lower for the BIAsp 30 group after breakfast (P = 0.003) and dinner (P = 0.033); post-lunch values were not significantly different. No major hypoglycemic episodes were recorded. Nocturnal hypoglycemia was reported by 25% of subjects in the BIAsp 30 group and by 10% in the insulin glargine group (P = 0.021). Weight gain was 5.6± 4.6 and 3.0 ± 4.3 kg (P = 0.0004) for BIAsp 30 and insulin glargine, respectively. Conclusions: BIAsp 30, given twice daily in combination with metformin, was more effective than insulin glargine, given once daily in combination with metformin, at controlling blood glucose in insulin-naïve patients with type 2 diabetes, but was associated with increased weight gain and minor hypoglycemic events.
Official journal of the South African Academy of Family Practice/Primary Care
Background There is increasing evidence that postprandial hyperglycaemia is implicated in the development of macro-and microvascular diabetic complications. Thus, control of postprandial glucose levels (PPG), in addition to control of fasting blood glucose (FBG), will ensure overall glycaemic control in diabetic patients. This study evaluated the effectiveness of a current anti-diabetic regimen on PPG in patients with type 2 diabetes mellitus. Method A total of 31 type 2 diabetic subjects on combination treatment of either Humulin N ® (HN), Monotard HM (ge) ® (M) or Humulin L ® (HL) insulin, with metformin, participated in a controlled, prospective, one-day visit study at a tertiary referral state diabetes clinic. The objective was to evaluate the effectiveness of the combination treatment of either M (n = 11) versus HN (n = 10) or HL (n = 10) insulin, each in combination with metformin, on PPG in this study cohort. Each subject was given a standardised meal after completing baseline procedures. Prescribed insulin doses were taken the night prior to the study day and metformin doses were taken with the standardised meal on the following morning, the study day. After completion of the meal, blood glucose levels were determined every half an hour at 0, 30, 60, 90, 120 and 150 minutes, thus providing a postprandial glucose profile for each subject. The data was analysed using ANOVA. Results The study cohort was South African, predominantly of Indian origin (54.8%), with a mean age of 59.2 ± 8 years, and 71% of the cohort was female. The subjects had a mean duration of diabetes of 11.4 ± 6.6 years, with 71% (n = 22) having a positive family history. The study cohort was obese (BMI 32.3 ± 6.2kg/m2, WHR 0.9 ± 0.1). A total of 61.3% (n = 19) of the study cohort was hypertensive, while 29% (n = 9) presented with at least one cardiovascular event and 48.3% (n = 15) had high total cholesterol. On entry to the study, the mean (± SD) FBG (10.3 ± 3.7mmol/l), fructosamine (369.9 ± 78.8mol/l) and glycosylated haemoglobin (9 ± 2%) were elevated. Each insulin group, HN, M and HL, was statistically matched for the above-mentioned and was therefore compared.
Clinical Therapeutics, 2008
The aim of this study was to describe glycemic control levels (fasting plasma glucose [FPG] and glycosylated hemoglobin [HbAI~]) and pharmacotherapy change patterns among a cohort of patients with type 2 diabetes mellitus (T2DM) receiving various antidiabetic agents. Methods: This study, a retrospective analysis conducted from a large electronic medical record database, identified T2DM patients with _>1 prescription for metformin, sulfonylureas, or thiazolidinediones from January 23, 1997, through March 15, 2006. The database contained medical and clinical records of patients-including diagnoses, medications, laboratory results, and physician orders-linked through encrypted patient identifiers. This study calculated the mean and median FPG and HbAI~ values (performed within 30 days before or after a pharmacotherapy change) and the percentage of patients with values above those recommended by the American Diabetes Association (ADA) and the American College of Endocrinology (ACE)/American Association of Clinical Endocrinologists (AACE). Results: The study included a total of 7769 T2DM patients (3942 female/3827 male; 56.9% were aged 50-69 years). For patients with no pharmacotherapy change, most did not achieve the ADA recommendations for FPG (56.4% [191713398]) or HbAlc (48.6% [95211958]) or the ACE/AACE recommendations for FPG (79.4% [269813398]) or HbAI~ (65.4% [12811 1958]). These patients' mean FPG level was 151.9 mg/ dL (95% CI, 150.0-153.9 mg/dL) and their mean HbAI~ value was 7.51% (95% CI, 7.43%-7.60%). For patients with a pharmacotherapy change, the mean FPG level was 191.1 mg/dL (95% CI, 186.7-195.4 mg/dL) and the mean HbAI~ value was 8.85% (95% CI, 8.70%-9.00%). Similar to those with no pharmaco-therapy change, a large percentage of patients with a pharmacotherapy change did not achieve the ADA recommendations for FPG (77.7% [1107/1425]) or HbAlc (76.2% [753/988]) or the ACE/AACE recommendations for FPG (90.1% [1284/1425]) or HbAlc (88.5% [874/988]). Conclusion: Despite the proven benefits of maintaining glycemic control and its impact on reducing long-term risk of diabetes complications, these results indicate that the mean FPG and HbAI~ values for a large percentage of diabetic patients included in this study remained above those recommended by the ADA and the ACE/AACE.
Clinical Therapeutics, 2004
Background: Injection of insulin lispro (LP) before meals provides a more physiologic insulin activity profile than regular human insulin, but the relatively short duration of action of LP may allow the blood glucose (BG) level to increase during the late postprandial period (4-7 hours after meals) unless basal insulin is optimally replaced. One approach to basal insulin optimization has been to combine small doses of NPH with LP before meals. When used in a similar fashion, premixed, fixed-ratio insulin preparations containing LP and NPL (an LP-based intermediate-acting insulin) may provide the basis for an optimized basal-bolus insulin regimen.