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

Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine for up to 39 months in adults and children with type 1 and adults with type 2 diabetes. In conclusion, insulin glargine is an effective and well tolerated basal insulin therapy when given as a single daily subcutaneous injection to patients with diabetes, with benefits in terms of glycaemic control and reduced frequency of hypoglycaemia over regimens based on conventional basal insulins. Accumulating data and official recommendations show the suitability of insulin glargine for first-line use in selected patients with type 2 diabetes who require insulin treatment, as well as in patients with type 1 disease, and confirm its use in children and adolescents.
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PMID:Insulin glargine: an updated review of its use in the management of diabetes mellitus. 1290 90

The initial injection in 1922 of a pancreatic extract, or insulin as it came to be known, into a patient with diabetes mellitus has since been followed by the successive introduction of longer-acting insulins, more highly purified insulins, and insulins that have been modified to more closely match insulin activity to patients' physiologic requirements. The recently introduced rapid-acting insulin analogues lispro and aspart and the long-acting analogue glargine are further refinements of insulin therapy. Current treatment strategies for severe insulin deficiency are based on the need to provide 2 components of insulin replacement: basal and postprandial. Rapid-acting insulin has been shown to provide superior postprandial glucose control compared with regular insulin. Truly effective control of basal insulin has been achieved by the introduction of the insulin pump in the 1980s and insulin glargine in 2001. Insulin glargine is the first insulin analogue to provide, in a majority of patients, a continuous level of insulin without a pronounced peak after a single daily injection, closely mimicking the normal pancreatic release of basal insulin in healthy individuals. Clinical experience is providing many insights into how basal and prandial components of insulin therapy can be best combined, although evidence from controlled trials will take some years to accumulate. Experience and observations since 2001 indicate that insulin therapy should be introduced earlier in patients with type 2 diabetes to control blood glucose levels. More importantly, the greatest benefit of insulin glargine has been to change positively the way physicians and patients think about insulin therapy. Newer insulin analogues, improved devices for home glucose monitoring, and pulmonary inhaled insulin are other innovations that promise improvement of hemoglobin A(1c) levels.
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PMID:Treatment of patients with severe insulin deficiency; what we have learned over the past 2 years. 1501 56

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.
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PMID:[Long-acting insulin analogs: progressing slowly]. 1556 34

Insulin glargine is a recombinant human insulin analog produced by DNA technology using a nonpathogenic strain of Escherichia coli. Two modifications of human insulin result in a stable molecule which is soluble in slightly acidic conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue. Because of these properties, absorption of insulin glargine is delayed and the analog provides a fairly constant, basal insulin supply without peaks in plasma insulin levels for approximately 24 hours, similar to that achieved by a continuous subcutaneous insulin infusion. Insulin glargine is indicated as a once daily subcutaneous injection to provide basal glycemic control in adults and children aged >6 years with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Fasting plasma glucose and fasting blood glucose levels generally improved to a greater extent in patients with type 1 diabetes mellitus receiving insulin glargine than patients who administered Neutral Protamine Hagedorn (NPH) insulin. In patients with type 1 or 2 disease, glycosylated hemoglobin levels were slightly reduced and to a similar extent with insulin glargine and NPH insulin. Most clinical trials in patients with type 1 or 2 diabetes mellitus demonstrated a lower incidence of hypoglycemia, especially nocturnal hypoglycemia, with insulin glargine compared with NPH insulin. One of the most common adverse events with insulin glargine treatment was injection site pain which, in some studies, occurred more frequently than in patients receiving NPH insulin. In all cases the symptoms were mild and treatment discontinuation was not required. Otherwise, the drug is well tolerated and does not appear to be immunogenic. In conclusion, insulin glargine once a day provides basal control of glycemia for approximately 24 hours without inducing peaks in plasma insulin levels in patients with type 1 or 2 diabetes mellitus. In long-term, well designed trials insulin glargine once daily improved glycemic control at least as effectively as NPH insulin given once or twice daily. The drug was well tolerated and in most studies the incidence of nocturnal hypoglycemia was significantly less in patients treated with insulin glargine compared with patients receiving NPH insulin. Therefore, insulin glargine is likely to be a useful addition to the armamentarium of insulin therapy by establishing basal glycemic control with once daily administration and a reduced risk of nocturnal hypoglycemia.
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PMID:Spotlight on insulin glargine in type 1 and 2 diabetes mellitus. 1576 21

The main goal of treatment of diabetes mellitus (DM) is to maintain long term near normoglycemia. Insulin therapy plays a pivotal role in the management of DM. Most insulin preparations and insulin delivery systems, do not mimic the physiological insulin secretion in the body, leading to impaired metabolic control and increased hypoglycemic attacks. Insulin glargine is newer, long acting insulin analog with duration of action of 24 hr. It practically does not show any peak over its duration of action. In various clinical trials, it has shown comparable/better efficacy than the currently used insulin replacement therapies with no increased side effects. In the current scenario, though it is difficult to achieve an ideal replacement therapy, insulin glargine is definitely a positive step in that direction.
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PMID:Insulin glargine: a long acting insulin analog. 1579 46

Insulin glargine (HOE 901) appears to be the first clinically useful extended-acting insulin preparation for 50 years. A combination of a di-arginine addition to the C-terminal of the insulin B-chain, and a glycine substitution in the A-chain, produce an insulin which is soluble at acid pH, but precipitates in sc. tissue at neutral pH after injection. This new insulin analogue has slightly lower receptor binding affinity compared to human insulin, but equal potency in vivo. Prolonged receptor binding is not found, and IGF-1 binding is not significantly different from human insulin. Glucose clamp and sc. disappearance studies confirm that insulin glargine has a much slower onset of effect than NPH (Neutral Protamine Hagedorn) insulin, and a much more protracted profile of action. Variability of absorption is difficult to assess from published studies, but is not dissimilar to NPH insulin. Patient studies in Type 1 and Type 2 diabetes published to date are inconclusive, but appear to confirm differences in pharmacokinetics between insulin glargine and NPH, with significantly lower fasting plasma glucose levels or reduction in night hypoglycaemia. No safety concerns have emerged. It thus appears that insulin glargine is a genuinely new addition to the insulin family, and with further clinical experience it may well be possible to achieve better basal blood glucose control (without enhanced risk of hypoglycaemia), particularly at night or in conjunction with rapid-acting insulin analogues.
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PMID:Insulin glargine: the first clinically useful extended-acting insulin in half a century? 1599 80

This study assessed the role of insulin glargine use on the short-term costs of diabetes care from a state Medicaid fee-for-service reimbursement perspective. A retrospective claims analysis was performed for 20% of Medicaid recipients in California (Medi-Cal) between November 2000 and September 2002. Each patient with continuous enrollment at least 6 months before and after the insulin glargine index date was matched with 2 reference patients by age, gender, diabetes diagnosis, and enrollment dates. Costs were calculated for emergency department, inpatient, outpatient, and pharmacy claims paid, and changes from baseline were determined. Incremental cost savings were estimated from baseline cost in the insulin glargine group multiplied by the difference in percentage of changes from baseline. Of the 1018 insulin glargine users, 267 satisfied inclusion criteria and were matched to 534 reference patients. Baseline treatment costs were 2.7-fold higher in the insulin glargine group. Absolute cost reductions in the insulin glargine and reference groups were 185 dollars and 72 dollars per patient, respectively. Incremental cost savings were 69 dollars per insulin glargine user, including more than 200 dollars in incremental savings for inpatient claims. Hypoglycemia decreased from 9.5% to 3.8% of inpatient claims in the insulin glargine group but remained 1.1% throughout in the reference group. Insulin glargine use was associated with reduced inpatient hypoglycemia-related claims paid and short-term reductions in the inpatient and total costs of diabetes-related care. Additional studies are warranted to assess the influence of insulin glargine on diabetes-related costs.
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PMID:Incremental cost savings 6 months following initiation of insulin glargine in a Medicaid fee-for-service sample. 1604 Nov 97

Insulin glargine is a biosynthetic human insulin analog which has been developed by Aventis Pharma (formerly Hoechst Marion Roussel, HMR), for the treatment of types I and II diabetes. In April 1999, HMR filed insulin glargine for approval in both Europe and the US [322507]. In April 2000, the FDA approved insulin glargine (as Lantus) for the treatment of adult patients with type II diabetes mellitus, who require basal insulin for the control of hyperglycemia, and for adult and pediatric patients with type I diabetes mellitus [363836]. Aventis expects to launch this product during 2000 [361988]. In June 2000, the EMEA approved insulin glargine for the treatment of both type I and II diabetes [370984]. In April 1999, the FDA recommended that HMR should initially submit 6-month efficacy and safety data, instead of the usual 12- month data, to hasten the FDA approval procedure. The rest of the phase III data would be added to the filing at a later date [279466]. Insulin glargine is in phase III trials in Japan as a substitute for basal insulin in the treatment of Type I diabetes [216445]. Two formulations of insulin glargine with zinc have also been tested in phase I trials. HOE-71/GT15 and GT80 contain 15 and 80 mu g/ml of zinc. These formulations appear to have longer duration of action with a reduced peak insulin effect [177507]. This insulin analog has a lower receptor binding affinity compared with human insulin, but shows equal potency in vivo [320724]. Insulin glargine was designated as a medium priority project by HMR, which means the project had been set tight deadlines which if not achieved, would have resulted in discontinuation [221118]. In April 2000, Novo Nordisk filed a complaint in Germany against Aventis claiming that the production and sale of insulin glargine infringes two German patents held by Novo Nordisk [364362]. In July 2000, Credit Lyonnais Securities Europe predicted that insulin glargine was likely to enjoy a strong competitive position for several years in Europe and the US, following launch in these territories during 2000, while it was predicted that a registration dossier would be submitted in Japn in 2002. Sales were predicted to reach Euro 600 million by 2005. In April 1999, ABN Amro predicted annual sales of DM 75 million in 2000, rising to DM 200 million in 2002 [328676].
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PMID:Insulin glargine (Aventis Pharma). 1604 68

Insulin glargine is a long-acting insulin analogue providing a more predictable and reproducible circulating insulin profile than other available basal insulin products. Hypoglycaemia is one of the main limiting factors to patients with diabetes requiring insulin, in achieving tight glycaemic control and reduced rates of complications. Evidence from randomised controlled clinical trials demonstrates reduced rates of hypoglycaemia in patients with type 1 and type 2 diabetes using insulin glargine compared with other basal insulin. Insulin glargine has been registered for use in New Zealand since June 2001, but currently remains unsubsidised by PHARMAC. Reducing the incidence and impact of diabetes is one of the stated aims in the New Zealand Health Strategy and the complete lack of funding for pharmaceutical agents such as insulin glargine severely limits its accessibility to patients with diabetes and would seem in contradiction to this aim.
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PMID:PHARMAC and long-acting insulin analogues: a poor man's insulin pump--but not available to the poor man. 1625 85

The stress of critical illness evokes insulin resistance and hyperglycemia. Artificial nutrition is commonly considered one of the main causes of hyperglycemia in hospitalized patients. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia Intensive insulin treatment to normalize blood glucose during feeding has been shown to improve morbidity and mortality in patients in intensive care. Insulin glargine may contribute to improving the glycemic values in patients receiving artificial nutrition with hyperglycemia.
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PMID:[Artificial nutrition in the patient with hyperglycemia]. 1666 45


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