Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens

Jehle, Peter; Micheler, Clemens; Jehle, Daniela R.; Breitig, D.; Boehm, Bernhard O.

doi:10.1016/s0140-6736(98)12459-5

Cited by 181 publications

(109 citation statements)

References 14 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, it has been shown that the need to thoroughly resuspend the NPH insulin before injection is often disregarded by patients with diabetes (21), which clearly contributes to the high variability of NPH insulin in clinical practice (22). In this study, appropriate resuspension of NPH insulin was ensured by experienced clinical staff.…”

Section: Discussionmentioning

confidence: 99%

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes

Heise

Nosek²,

Rønn³

et al. 2004

Diabetes

573

461

View full text Add to dashboard Cite

The aim of this randomized double-blind study was to compare the within-subject variability of the glucoselowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 ؎ 10 years [ D aily clinical experience indicates that subcutaneous administration of insulin often does not result in a reproducible metabolic effect even when injected at the same dose under comparable conditions. Nonetheless, only few studies have assessed the variability of insulin absorption after subcutaneous administration (1-7), and even fewer have assessed the variability in the glucose-lowering effect of insulin. Thus, even though variability of the glucoselowering effect is regarded as a major obstacle to achieving optimal metabolic control (8 -10), our knowledge of the variability of insulin preparations is surprisingly scarce (11,12). This is particularly true for basal insulin preparations. The few studies available report coefficients of variation (CVs) for within-and between-subject variability in the pharmacodynamic action of long-acting zinc insulin preparations to be between 35 and 55% (9) and even greater for NPH insulin (13). Compared with these findings, the variability (CV) of short-acting insulin preparations, which are reported in the range of "only" 20 -30% (10,11), are less of a concern. The development of the new long-acting insulin analogs such as insulin detemir and insulin glargine has raised the hope of concurrent lower within-subject variability. However, insulin glargine does not appear to provide any improvement in the within-subject variability compared with NPH insulin (8).The aim of this study was to compare the within-subject variability in the glucose-lowering effect of the novel long-acting insulin analog insulin detemir with that of NPH insulin and insulin glargine. Insulin detemir [Lys B29 (N ε -tetradecanoyl) des(B30) human insulin] is the first of a new class of long-acting soluble insulin analogs. Its prolonged duration of action is attributable to a combination of increased self-association (hexamer stabilization and hexamer-hexamer interaction) and albumin binding due to acylation of the amino acid lysine in position B29 with a 14 C fatty acid (myristic acid). Insulin detemir is highly albumin bound in the interstitial fluid and in plasma (14) and has been shown to elicit a protracted metabolic action, with a slow onset of action and a less pronounced peak of action compared with that observed for NPH insulin (15,16).

show abstract

Section: Discussionmentioning

confidence: 99%

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes

Heise

Nosek²,

Rønn³

et al. 2004

Diabetes

573

461

View full text Add to dashboard Cite

show abstract

“…Incomplete resuspension by patients has been shown to be a major source of variability. [22][23][24] Furthermore, even the mean absorption profiles of these conventional basal insulins are far from ideal. 23 NPH insulin, for example, is characterised by a peak in the pharmacokinetic profile 4-6 h after injection followed by a steady decline, rather than a low and constant absorption.…”

Section: The Rationale For a Basal Insulin Analoguementioning

confidence: 99%

Engineering predictability and protraction in a basal insulin analogue: the pharmacology of insulin detemir

Kurtzhals

2004

Int J Obes

106

View full text Add to dashboard Cite

The suboptimal nature of the absorption profiles of human insulin formulations following subcutaneous administration has prompted the development of insulin analogues better suited for therapeutic use in diabetes mellitus. A particular challenge has been to engineer long-acting agents that do not produce unduly variable responses from one injection to another. One recent approach that has met with success has been to acylate, the insulin molecule with a fatty acid, thereby enabling reversible albumin binding. The first clinically available agent of this type is insulin detemir. Pharmacological studies have established that this principle is effective in prolonging action, primarily by retarding absorption. The solubility of insulin detemir in the vial and after injection and an important buffering mechanism effected by plasma albumin binding explain a significant decrease in within-subject variability of pharmacodynamic response observed in repeat isoglycaemic clamp studies where insulin detemir was compared to other basal insulin products. Owing to the extremely high ratio of albumin-binding sites to insulin detemir molecules at therapeutic concentrations, no safety considerations have been identified pertaining to albumin binding. The insulin detemir molecule retains the molecular pharmacological properties of native human insulin, including a physiological balance between metabolic and mitogenic potencies. Thus, insulin detemir offers the promise of an improved tolerability:efficacy ratio in the clinical setting.

show abstract

“…[1][2][3][4] This may make it difficult to achieve stable glycemic control over 24 hours, as both the variability and pronounced peak can result in unexpected hyperglycemia or hypoglycemia.…”

Section: Introductionmentioning

confidence: 99%

Comparison of insulin detemir and insulin glargine in a basal—bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: A 52-week, multinational, randomized, open-label, parallel-group, Treat-to-Target noninferiority trial

Heller

Koenen

Bode

2009

Clinical Therapeutics

View full text Add to dashboard Cite

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. 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. Results Conclusion

show abstract

Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens

Cited by 181 publications

References 14 publications

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes

Engineering predictability and protraction in a basal insulin analogue: the pharmacology of insulin detemir

Comparison of insulin detemir and insulin glargine in a basal—bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: A 52-week, multinational, randomized, open-label, parallel-group, Treat-to-Target noninferiority trial

Contact Info

Product

Resources

About