Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin glargine is an extended-action biosynthetic human insulin. It precipitates in the neutral environment of subcutaneous tissue and is thus gradually absorbed into the bloodstream. The addition of small amounts of zinc to the formulation further delays absorption. In small euglycaemic clamp studies, the onset of action of insulin glargine was shown to be later, the duration of action longer and the time-action profile flatter than that of Neutral Protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus and healthy volunteers. Four large clinical trials of up to 28 weeks' duration have shown that a single bedtime dose of insulin glargine, in combination with preprandial short-acting insulin, is as effective or more effective than once or twice daily NPH plus short-acting insulin in improving glycaemic control in patients with type 1 diabetes mellitus. In 3 large comparative trials, insulin glargine decreased glycosylated haemoglobin and/or fasting blood glucose levels to a similar extent to that seen with NPH insulin in patients with insulin-dependent or non-insulin-dependent type 2 diabetes mellitus, either as monotherapy or in combination with oral hypoglycaemic agents. Insulin glargine appears to be well tolerated. A lower incidence of hypoglycaemia, especially at night, was reported in most trials with insulin glargine when compared with NPH insulin.
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PMID:Insulin glargine. 1073 May 48

The DCCT and UKPDS studies have definitely established that in type 1 as well as in type 2 diabetes mellitus, long-term near-normoglycaemia strongly protects against onset and/or progression of microangiopathic complications. Therefore, implementation of insulin strategies to maintain long-term near-normoglycaemia is of key importance in the management of diabetes mellitus. To successfully reach the goal of near-normoglycaemia, insulin therapy has to be physiological, i.e. it has to mimic nature by providing a bolus of insulin at meal ingestion, and by replacing the need for basal insulin between meals and during the night. The meal-time insulin needs can be best met by s.c. injection of a short-acting insulin analogue (lispro, aspart). Short-acting insulin analogues should be preferred to human regular insulin for three main reasons. First, convenience (meal-time injection, better adaptation of insulin dose to carbohydrate content of the meal); second, lower blood glucose 2-hour after meals; third, less risk for late post-prandial hypoglycaemia. However, the benefits of meal-time treatment with short-acting insulin analogues become apparent only by the extent to which replacement of basal insulin is optimised as well. The interprandial (especially nocturnal) need for basal insulin can be best met by the continuous s.c. insulin infusion by an external minipump, the gold standard of basal insulin replacement. Continuous s.c. insulin infusion in the basal state is so good because it uses a short-acting insulin analogue (low variability in s.c. absorption, flat and peak-less action profile), not insulin preparations with retarded action (high variability of s.c. absorption, peak of action) likewise the model of multiple daily insulin injections. A second choice option is s.c. injection of an insulin preparation with retarded action. At present, the long-acting insulin analogue glargine is the retarded insulin preparation of choice because its action profile is flat, peakless and long-lasting (approximately 24 hours). This is in contrast with the peak action profile of NPH insulin which exhibits a short duration of action (10-15 h). Thus, the modern insulin strategies for intensive therapy always include use of a short-acting insulin analogue at meal-time, and use of either continuous s.c. insulin infusion, or a s.c. injection of insulin glargine to replace basal insulin. Insulin glargine reproduces closely the pharmacokinetics and pharmacodynamics of continuous s.c. insulin infusion, and should always be preferred to NPH in all insulin-requiring diabetic patients, both type 1 and type 2.
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PMID:Physiological insulin replacement in type 1 diabetes mellitus. 1146 May 80

Modern diabetes therapy is positively introduced insulin administration including intensive insulin therapy to type 1 and type 2 diabetes to prevent or delay the development of long-term complications. However, conventional insulin derivatives could not mimic more closely physiological insulin secretion profiles, resulting in frequent hypoglycemia attacks and brittle diabetes. Recent advanced technologies have allowed to modify insulin molecules to obtain several insulin analogues. Lys.Pro insulin and insulin aspart, rapid-acting insulin analogues, have demonstrated improved post-prandial glucose control in comparison with regular insulin, even although they are usually administered immediately prior to the meal. Insulin glargine and SoLongln, long-acting insulin analogues, could preserve the stable basic insulin profiles during a day as compared with NPH insulin. These insulin analogues are very useful to supply the post-prandial and basic insulin secretions in type 1 and type 2 diabetics.
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PMID:[Recent trends of development of rapid-acting and long-acting human insulin analogues--its biological characteristics and clinical availability]. 1171 96

The pharmacodynamics, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of insulin glargine are reviewed. Current treatment regimens for patients with type 1 diabetes mellitus and some with type 2 are designed to provide a basal insulin level with intermittent preprandial insulin coverage. Insulin glargine precipitates after subcutaneous injection, slowing absorption. Insulin glargine is used as a basal insulin and exhibits a flat pharmacokinetic profile, with a duration of action of at least 24 hours. Hypoglycemia is the most commonly reported adverse effect, especially within the first four weeks after a switch to insulin glargine. Insulin glargine should not be mixed with any other insulin product and should be administered with a syringe that has not been used for other insulin products or other medications. Insulin glargine is administered once daily at bedtime. Patients previously receiving twice-daily isophane insulin (NPH) should receive an insulin glargine dosage 20% less than the total daily dose of NPH insulin. Clinical trials did not consistently show improvements in hemoglobin A1c levels when patients with type 1 diabetes mellitus were switched from NPH insulin once or twice daily to insulin glargine. Insulin glargine should be considered for patients who continue to have elevated morning blood glucose levels and problems with nocturnal hypoglycemia despite receiving NPH insulin at bedtime. In patients with type 2 diabetes mellitus, insulin glargine significantly improved glycemic control compared with once-daily NPH insulin, but not when it was compared with combined treatment with once- or twice-daily NPH insulin. Clinical trials assessing progression of retinopathy and nephropathy and comparing insulin glargine therapy with continuous subcutaneous insulin infusion therapy are needed to more clearly determine insulin glargine's role. Insulin glargine is a new long-acting formulation that can provide prolonged basal glucose control in patients with diabetes mellitus.
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PMID:Insulin glargine: a new long-acting insulin product. 1194 2

Insulin glargine (Lantus) is a long-acting, human insulin analogue that has been specifically designed to overcome the deficiencies of traditionally available 'intermediate-acting' insulins that are currently used for basal insulin supplementation. In contrast to NPH insulin, subcutaneous insulin glargine injected once daily provides a relatively constant basal level of circulating insulin with no pronounced peak. In patients with type 1 and type 2 diabetes, once-daily insulin glargine achieves equivalent glycaemic control to NPH insulin given once or twice daily In patients with type 1 diabetes, it is associated with significantly lower fasting blood glucose (FBG) levels, especially in those patients previously on twice-daily NPH insulin. Insulin glargine is well tolerated and elicits less hypoglycaemia, especially nocturnal episodes, than NPH insulin, with similar levels of glycaemic control. This benefit is seen in patients with both type 1 and type 2 diabetes, in particular those previously on a once-daily NPH insulin regimen. Patients with type 1 and type 2 diabetes have also reported higher levels of treatment satisfaction when treated with insulin glargine. Insulin glargine provides the opportunity to achieve target blood glucose levels more effectively and safely compared with NPH insulin, due to the reduced risk of hypoglycaemia, especially nocturnal hypoglycaemia. Insulin treatment needs to be individualised, with the dose of insulin glargine adjusted according to the blood glucose level as part of an aggressive regimen in an attempt to achieve near normoglycaemia without incurring episodes of hypoglycaemia. Insulin glargine should be used in combination with short-acting insulin analogues in patients with type 1 diabetes. In patients where oral hypoglycaemic agents are failing, insulin glargine can be added. The early introduction of insulin in patients with type 2 diabetes is to be encouraged.
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PMID:Insulin glargine (Lantus). 1216 45

The DCCT and UKPDS have established that in type 1 and in type 2 diabetes respectively, long-term near-normoglycaemia protects against the onset and/or progression of microangiopathic complications. Therefore, insulin strategies to maintain long-term near-normoglycaemia are of key importance in the management of diabetes. To successfully achieve near-normoglycaemia, insulin therapy must mimic nature by providing a bolus of insulin at meal ingestion and by replacing basal insulin between meals and overnight Mealtime insulin needs can be best met by subcutaneous (s.c.) injection of a rapid-acting insulin analogue such as insulin lispro or insulin aspart. Rapid-acting insulin analogues are preferred to human regular insulin for three reasons: convenience (meal-time injection, better adaptation of insulin dose to carbohydrate content of the meal); lower blood glucose 2 hours after meals; and less risk for late postprandial hypoglycaemia. However, in type 1 diabetes the benefits of mealtime treatment with rapid-acting insulin analogues become apparent only to the extent that replacement of basal insulin is optimised. The interprandial need for basal insulin can be best met by continuous s.c. insulin infusion (CSII). CSII is very good for basal insulin replacement because it uses a rapid-acting insulin analogue with low variability in s.c. absorption, resulting in a flat and peakless action profile. A second option for basal insulin replacement is s.c. injection of an insulin preparation with retarded action. The two most commonly used are NPH and insulin glargine. NPH exhibits an action profile with a peak 4 to 5 hours after injection and duration of action of 10 to 15 hours. Insulin glargine has a peakless action profile and lasts approximately 24 hours. To optimise replacement of basal insulin with NPH, a few units of NPH must be combined with rapid-acting analogues at meals and also given at bedtime (0.2 U/kg). With insulin glargine, 0.2 to 0.4 U/kg should be injected once or, in some patients, twice daily. Modern insulin strategies for intensive therapy should include use of a rapid-acting insulin analogue at meal-time, and use of CSII to replace basal insulin. Insulin glargine reproduces closely the pharmacokinetics and pharmacodynamics of CSII and should be considered for substitution of basal insulin, especially in type 1 diabetes.
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PMID:Clinical strategies for controlling peaks and valleys: type 1 diabetes. 1216 10

Insulin glargine is an innovative, long-acting human insulin analogue, whose prolonged mean activity profile has no pronounced peak. Accordingly, it mimics more closely the natural physiological profile of basal endogenous insulin secretion than do traditional extended-acting insulins such as NPH insulin. As would be expected for a more satisfactory basal insulin, clinical trials comparing insulin glargine with NPH insulin show less nocturnal hypoglycaemia, improved pre-breakfast blood glucose levels, or both. Furthermore, no substantive safety concerns have emerged for insulin glargine. Thus, insulin glargine represents the first major advance in the provision of basal insulin injection therapy for people with type 1 and type 2 diabetes for over 50 years.
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PMID:An overview of insulin glargine. 1232 87

The United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regimens has the potential to significantly reduce the risk for long-term microvascular complications of type 2 diabetes. An important question that remains to be answered is what is the best approach to optimizing glycemic control in patients with this disease. This article reviews results of studies in which insulin was used alone or in combination with oral antidiabetic agents for treatment of patients with type 2 diabetes. Analysis of comparative studies (13 in insulin-naive and 26 in previously insulin-treated patients) showed that combination therapy involving one to two insulin injections per day plus oral therapy is usually more effective than insulin monotherapy for achieving and maintaining glycemic control. Combination treatment for type 2 diabetes can be significantly improved by newly developed preparations that lack the major limitations of older products. Once-daily administration of isophane insulin (NPH insulin) is limited by a 15-18-h duration of action and a peak effect that occurs about 6 h after injection. Insulin glargine, a new insulin analogue developed using recombinant DNA technology, has a flat pharmacodynamic profile and a 24-h duration of action. Results from a recent comparative study indicate that insulin glargine plus oral therapy may provide better post-dinner glucose control as well as less symptomatic and nocturnal hypoglycemia than oral therapy combined with NPH insulin. The studies reviewed in the present article support the conclusion that combination therapy with insulin glargine combined with one or more oral antidiabetic agents may be the treatment of choice for achieving glycemic control in patients with type 2 diabetes.
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PMID:Combination therapy with insulin and oral agents: optimizing glycemic control in patients with type 2 diabetes mellitus. 1232 90

Optimal glucose control is the primary goal for treating diabetes mellitus and preventing long-term complications of diabetes, such as coronary heart disease, nephropathy, neuropathy and retinopathy. Insulin glargine is a novel, long-acting human insulin analog that is indicated in type 1 diabetic patients aged >or=6, or in type 2 diabetic patients who require basal insulin for glycemic control. Insulin glargine is a recombinant insulin with a modified structure that allows it to dissolve in an acidic solution, but to precipitate in the physiological subcutaneous tissue forming a depot effect. In contrast to Neutral Protamine Hagedorn (NPH) insulin, insulin glargine has a slower onset, a longer duration of action, and no peak in metabolic activity. Once-daily subcutaneous administration of insulin glargine at bedtime has comparable efficacy to that of NPH insulin once or twice daily when used in combination with bolus insulin in type 1 diabetic patients, or in conjunction with oral antidiabetic drugs in type 2 diabetic patients. Overall, insulin glargine has similar adverse effects when compared with NPH insulin. Insulin glargine has been associated with less nocturnal hypoglycemia and improved treatment satisfaction in several clinical trials with durations of < 52 weeks. Pharmacoeconomic analysis comparing insulin glargine with other intermediate- or long-acting insulin preparations used as basal insulin therapy has not been performed. In summary, insulin glargine offers a promising alternative as a once-daily basal insulin therapy in patients with type 1 and type 2 diabetes.
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PMID:Insulin glargine: a new once-daily basal insulin for the management of type 1 and type 2 diabetes mellitus. 1278 37

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


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