Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin detemir (NN-304) is a soluble, long-acting insulin analog being developed by Novo Nordisk for the potential treatment of type 1 and 2 diabetes. As of February 2003, Novo Nordisk was expecting both US and EU approval in the first half of 2004. In December 2002, Novo Nordisk submitted an NDA to the FDA and an NDS to the Canadian Biologics & Genetics Therapeutic Directorate for the approval of insulin detemir for the treatment of diabetes mellitus.
 ...
PMID:Insulin detemir. Novo Nordisk. 1280 86

The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering 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 [mean +/- SD], BMI 24 +/- 2 kg/m(2), HbA(1c) 7.5 +/- 1.2%, diabetes duration 18 +/- 9 years) participated in this parallel group comparison. Each subject received four single subcutaneous doses of 0.4 units/kg of either insulin detemir (n = 18), insulin glargine (n = 16), or human NPH insulin (n = 17) under euglycemic glucose clamp conditions (target blood glucose concentration 5.5 mmol/l) on four identical study days. The pharmacodynamic (glucose infusion rates [GIRs]) and pharmacokinetic (serum concentrations of insulin detemir, human insulin, and insulin glargine) properties of the basal insulin preparations were recorded for 24 h postdosing. Insulin detemir was associated with significantly less within-subject variability than both NPH insulin and insulin glargine, as assessed by the coefficient of variation (CV) for the pharmacodynamic end points studied [GIR-AUC((0-12 h)) 27% (detemir) vs. 59% (NPH) vs. 46% (glargine); GIR-AUC((0-24 h)) 27 vs. 68 vs. 48%; GIR(max) 23 vs. 46 vs. 36%; P < 0.001 for all comparisons]. Insulin detemir also provided less within-subject variability in the pharmacokinetic end points: maximal concentration (C(max)) 18 vs. 24 vs. 34%; INS-AUC((0- infinity )) 14 vs. 28 vs. 33%. The results suggest that insulin detemir has a significantly more predictable glucose-lowering effect than both NPH insulin and insulin glargine.
Diabetes 2004 Jun
PMID:Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. 1516 70

Tight glycaemic control is essential for reducing the risk of long-term diabetic complications in people with type I or II diabetes. Intensive blood-glucose control attempts to normalise both pre- and postprandial glycaemia, while avoiding severe hypoglycaemia. A basal insulin, providing a low level of insulin to cover postprandial and overnight fasting periods, is central to intensive blood-glucose control. However, hypoglycaemia, particularly nocturnal hypoglycaemia, is a major treatment-related complication of therapy with most basal insulins currently available for use in clinical practice. This is a result of pronounced peaks in absorption, which lead to inappropriate hyperinsulinaemia following evening administration, and especially poorly reproducible pharmacokinetic profiles when injected subcutaneously. Indeed, for many patients and health-care providers, concern around hypoglycaemia forms a critical barrier to the attainment of tight glycaemic control. Insulin detemir is a novel long-acting analogue of human insulin designed to overcome these practical limitations. Clinical evidence from comparative studies with NPH insulin shows that insulin detemir provides a consistent and clinically relevant reduction in hypoglycaemic risk, especially for nocturnal events, at equivalent or better levels of glycaemic control.
 ...
PMID:Can we reduce hypoglycaemia with insulin detemir? 1530 36

In the treatment of diabetes, the positive correlation between weight gain and glycaemic control is well known. Inappropriate weight gain has been demonstrated in landmark diabetes studies, with insulin or oral antidiabetic drugs. Weight increase is associated with accelerated deterioration in beta-cell function in type II diabetes, and increases in hypertension and lipid levels in both type I and type II diabetes. Concerns about increasing weight may be a barrier to initiation or to intensification of insulin therapy. Insulin introduction may be delayed in type II diabetes, and patients may under-dose their insulin to avoid gaining weight. Insulin detemir is a new long-acting soluble insulin analogue where protraction is achieved by reversible binding to albumin. As a result, it has consistent absorption and low variability from injection to injection. Studies of insulin detemir in basal-bolus regimens in type I and type II diabetes have shown significantly less weight gain compared with NPH. There is speculation about potential mechanisms for these outcomes and results from ongoing investigations are awaited. The insulin detemir data suggest that weight gain with insulin therapy is not inevitable. The potential therefore exists for improving glycaemic control while maintaining weight stability, resulting in immediate and long-term benefits for patients.
 ...
PMID:At last, a weight neutral insulin? 1530 37

Insulin therapy has been strongly influenced by the results of the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS), both of which support intensive antidiabetic therapy. Conventional insulin therapy can be limited, due to the difficulty in achieving tight glycemic control in people with diabetes, which is crucial to reducing the risk of long-term complications associated with diabetes. In recent years, three short-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting (insulin glargine and insulin detemir) recombinant analogues of regular human insulin have been developed for the management of diabetes. Short-acting insulin analogues are an alternative to regular human insulin before meals. Compared with regular human insulin, these new short-acting insulin analogues show faster subcutaneous absorption, a more rapid onset of activity and a shorter duration of action. As a result of these pharmacokinetic differences, an improved postprandial glycemic control is achieved, without increasing the risk of hypoglycemia. In addition, these insulin analogues can be administered immediately before a meal, thereby synchronizing insulin administration and food absorption. The long-acting insulin analogue insulin glargine was developed to provide basal insulin levels for 24 h when administered once daily at bedtime. Compared with previous intermediate- or long-acting conventional insulin, insulin glargine shows a flat profile of plasma insulin levels with no prominent peak. The use of this long-acting insulin analogue appears to be associated with a reduced incidence of hypoglycemia, especially at night. Insulin detemir is another basal insulin that may reduce nocturnal hypoglycemia and variability in glycemic values. The availability of these new insulin analogues has the potential to significantly improve long-term control over blood glucose in diabetic patients.
 ...
PMID:Insulin analogues in the management of diabetes. 1534 39

In the last few years short-acting insulin analogs have become increasingly popular. Their introduction has unmasked serious deficiencies in the capacity of isophane insulin to provide a stable basal insulinaemia. The long-acting insulin analogs, insulin glargine and insulin detemir, have been developed as alternatives to isophane insulin. Insulin glargine has a long duration of action and has demonstrated its usefulness in diabetes type 2, specifically a lower incidence of (nocturnal) hypoglycaemia compared to isophane insulin, in clinical practice. Insulin detemir has a very low variability in absorption and also seems to reduce the risk of nocturnal hypoglycaemia in diabetes type 1. More studies are, however, needed. Because of the higher costs of these novel insulins, the decision to switch a patient from isophane insulin to an insulin analog has to be made on an individual basis.
 ...
PMID:[Long-acting insulin analogs: progressing slowly]. 1556 34

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged and consistent metabolic effect of up to 24 hours in patients with type 1 or type 2 diabetes mellitus. Insulin detemir has a more predictable, protracted and consistent effect on blood glucose than neutral protamine Hagedorn (NPH) insulin, with less intrapatient variability in glycaemic control, compared with NPH insulin or insulin glargine. Insulin detemir, administered once or twice daily, is at least as effective as NPH insulin in maintaining overall glycaemic control, with a similar or lower risk of hypoglycaemia, especially nocturnal hypoglycaemia, compared with NPH insulin in patients with type 1 or type 2 diabetes. Insulin detemir also provides the added clinical benefit of no appreciable bodyweight gain in patients with type 1 diabetes and less bodyweight gain than NPH insulin in patients with type 2 diabetes. Insulin detemir is, therefore, a promising new option for basal insulin therapy in patients with type 1 or 2 diabetes.
 ...
PMID:Insulin detemir: a review of its use in the management of type 1 and 2 diabetes mellitus. 1551 57

Insulin detemir (Levemir) is a soluble long-acting human insulin analog acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged and consistent metabolic effect of up to 24 hours in patients with type 1 or type 2 diabetes mellitus. Insulin detemir has a more predictable, protracted, and consistent effect on blood glucose than neutral protamine Hagedorn (NPH) insulin, with less intrapatient variability in glycemic control than NPH insulin or insulin glargine. Insulin detemir, administered once or twice daily, is at least as effective as NPH insulin in maintaining overall glycemic control, with a similar or lower risk of hypoglycemia, especially nocturnal hypoglycemia, compared with NPH insulin in patients with type 1 or type 2 diabetes. Insulin detemir also provides the added clinical benefit of no appreciable bodyweight gain in patients with type 1 diabetes and less bodyweight gain than NPH insulin in patients with type 2 diabetes. Insulin detemir is, therefore, a promising new option for basal insulin therapy in patients with type 1 or 2 diabetes.
 ...
PMID:Spotlight on insulin detemir in type 1 and 2 diabetes mellitus. 1569 Dec 19

Basal insulin therapy is an integral part of the intensive management of type 1 diabetes and it is also often used in type 2 diabetes. An ideal insulin regimen in patients with diabetes would mirror the 24-h insulin profile of a non-diabetic person, thereby preventing hyperglycaemia without inducing hypoglycaemia. Until recently, available insulins have pharmacokinetic disadvantages, compared to physiological insulin secretion. Insulin detemir is a new basal insulin analogue recently available for commercial use in the UK. Clinical trials have demonstrated lower fasting plasma glucose levels, lower variability in plasma glucose, predictable action profile and a reduced risk of nocturnal hypoglycaemia and weight gain, compared to conventional basal insulins. This study reviews the properties and potential use of insulin detemir.
Diabetes Obes Metab 2006 Jan
PMID:Insulin detemir: a new basal insulin analogue. 1636 79

Insulin treated diabetic patients have often to contend with variability in the action of injected insulin and to some unpredictibility in glycemic control. The variability in blood glucose control seems particularly important with long-acting insulins. Insulin detemir belongs to a new class of non-crystalline form of long-acting insulin analogs. Absorption of insulin detemir is dependent on neither appropriate resuspension before injection and dissolution of crystals in the subcutaneous tissue, as is the case for NPH insulin, nor on formation and dissolution of microprecipitates, as is the case for insulin glargine. In euglycemic glucose clamp studies, insulin detemir was associated with significantly less within-subjects variability for the pharmacodynamic endpoints than both NPH insulin and insulin glargine. Three, up to 6 months trials, carried out in patients with type 1 diabetes have shown that the day-to-day within-subject variations in plasma glucose were significantly lower with insulin detemir than with human NPH insulin. Similar results have been reported in patients with type 2 diabetes. Nightly 8-h plasma glucose recordings showed a smoother and more stable profile with insulin detemir than with NPH insulin. In patients with type 1 diabetes the combination of insulin detemir with mealtime insulin aspart, a fast-acting insulin analog, provides a smoother and more stable profile with lower post-prandial plasma glucose levels that the combination of NPH insulin with regular human insulin before each meal. In several trials, the risk of hypoglycemia, particularly of nocturnal hypoglycemia, was significantly lower with insulin detemir than with NPH insulin. In conclusion insulin detemir offers a better reproducibility as compared with other basal insulins, reduces the risk of hypoglycemia, and may lead the patients to titrate their insulin doses more easily and therefore to achieve more often glycemic objectives. The combination of rapid- and long-acting insulin analogs reproduces a more physiological insulin secretion and thereby reduces the risk of hypoglycemia and improves the overall 24-h glycemic profile.
Diabetes Metab 2005 Sep
PMID:Is insulin detemir able to favor a lower variability in the action of injected insulin in diabetic subjects? 1638 96


1 2 3 4 5 6 Next >>