Effects of multiple daily injection therapy with humalog mixtures versus separately injected insulin lispro and NPH insulin in adults with type I diabetes mellitus (original) (raw)
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Diabetic Medicine, 2004
Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH. One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment. Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05). The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.
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.
Journal of Diabetes and Its Complications, 2007
Objective: Two insulin regimens were used to explore acute and chronic postprandial changes in glycemia, lipemia, and metabolic markers associated with increased risk of cardiovascular disease. Methods: An open-label, randomized, two-period crossover study (12 weeks/period) compared a prandial regimen [premeal insulin lispro + bedtime neutral protamine Hagedorn (NPH)] with a basal regimen (twice-daily NPH). There were 30 patients (12 women and 18 men; mean age=61 years) with type 2 diabetes mellitus (mean duration=16 years) who were randomized after a 2-month lead-in with twice-daily NPH treatment. A standard lunch test meal developed according to each patient's caloric needs was administered at the end of each treatment period. Results: Insulin lispro was associated with significantly lower postprandial glucose (area under the curve 0-5 h =43.54 vs. 57.65 mM/h; Pb.001), elevated insulin concentrations, and acutely altered lipid fractions that included an early decrease followed by an increase in free fatty acids, lower triglycerides, elevated total cholesterol, elevated lowdensity lipoprotein cholesterol (LDL), and elevated high-density lipoprotein cholesterol. After 12 weeks of treatment, insulin lispro + bedtime NPH reduced hemoglobin A 1c (HbA 1c ; meanFSE=7.6F0.2 vs. 8.2F0.2%; Pb.001) without increasing hypoglycemia or insulin dose as compared with twice-daily NPH. Furthermore, treatment with the prandial insulin regimen resulted in lower total cholesterol, lower LDL cholesterol, and lower oxidized LDL. Conclusion: Improved postprandial glycemic control, as observed in a regimen containing both prandial insulin lispro and NPH as the basal insulin, is associated with significantly lower HbA 1c and acute modulation of lipid fractions after a test meal. These biochemical modifications may potentially have a favorable impact on cardiovascular risk in patients with type 2 diabetes mellitus. D
Clinical Therapeutics, 2009
Objective: The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basalbolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type 1 diabetes mellitus (T1DM). Methods: This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged ≥18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA 1c) value ≤11.0%. Patients were randomized in a 2:1 ratio to receive either detemir given once or twice daily or glargine given once daily for 52 weeks. The basal insulin was initially administered once daily (in the evening) in both groups; if patients in the detemir group were achieving the PG target before breakfast but not before dinner, they were switched to twice-daily administration. Each patient attended 13 study visits and received 16 scheduled telephone calls from the trial site. The primary efficacy end point was glycemic control (HbA 1c) after 52 weeks of treatment. Secondary end points included the number of patients achieving an HbA 1c value ≤7.0%, with or without a major hypoglycemic episode in the last month of treatment; fasting plasma glucose (FPG); within-patient variation in self-monitored plasma glucose (SMPG) before breakfast and dinner; and 10-point SMPG profiles. The noninferiority margin was 0.4%, consistent with US Food and Drug Administration guidelines. Results: Four hundred forty-three patients received study treatment (mean [SD] age, 42 [12] years; body mass index, 26.5 [4.0] kg/m 2 ; duration of diabetes, 17.2 [11.4] 3 years; HbA 1c , 8.1% [1.1%]). After 52 weeks, the estimated mean HbA 1c did not differ significantly between the detemir and glargine groups (7.57% and 7.56%, respectively; mean difference, 0.01%; 95% CI,-0.13 to 0.16), consistent with the noninferiority of detemir to glargine. The corresponding estimated changes in HbA 1c were-0.53% and-0.54%. In the 90 patients who completed the trial on once-daily and the 173 patients who completed the trial on twice-daily detemir, the estimated changes in HbA 1c were-0.45% and-0.56%, respectively. After 52 weeks, there were no significant differences in the proportion of those receiving detemir and glargine who achieved an HbA 1c value ≤7.0% without major hypoglycemia (31.9% and 28.9%, respectively). In addition, there were no significant differences in estimated mean FPG (8.58 and 8.81 mmol/L; mean difference,-0.23; 95% CI,-1.04 to 0.58) or in basal insulin doses. The basal insulin dose was numerically higher in patients receiving detemir twice rather than once daily (0.47 vs 0.33 U/kg, respectively). The relative risks for total and nocturnal hypoglycemia with detemir versus glargine were 0.94 and 1.12, respectively (both, P = NS). Six patients (2.0%) in the detemir group and 4 (2.8%) in the glargine group withdrew due to adverse events. Conclusion: During 52 weeks of basal-bolus therapy in patients with T1DM, detemir was noninferior to glargine in terms of overall glycemic control (HbA 1c), occurrence of hypoglycemia, and tolerability when used according to the approved