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Insulin Analogues Advantages

Pharmacokinetic And Pharmacodynamic Advantages Of Insulin Analogues And Premixed Insulin Analogues Over Human Insulins: Impact On Efficacy And Safety

Pharmacokinetic And Pharmacodynamic Advantages Of Insulin Analogues And Premixed Insulin Analogues Over Human Insulins: Impact On Efficacy And Safety

Abstract Human insulin preparations administered to patients with diabetes mellitus fail to reproduce the normal physiologic pattern of insulin secretion. Modifications have been made in the amino acid sequence of the insulin molecule with the aim of overcoming the pharmacokinetic shortcomings of human insulins. Such modifications have produced long-acting analogues, with relatively flat time–action profiles, for controlling glycemic levels between meals; and rapid-acting analogues with a fast onset and short duration of action, for controlling postprandial hyperglycemia. Premixed formulations of the rapid-acting analogues, containing both rapid-acting soluble and intermediate-acting protaminated forms, are also available. Trials of long-acting insulin analogues have consistently shown efficacy in controlling fasting plasma glucose and glycosylated hemoglobin (HbA1c), as well as a markedly reduced risk of hypoglycemia compared with neutral protamine Hagedorn insulin. The rapid-acting and premixed analogues offer better control of postprandial glucose excursions than do regular human insulin, resulting in similar or lower HbA1c levels. Furthermore, the analogues can offer patients greater flexibility and more convenience in administration compared with human insulins. This review provides an overview of the insulin analogues available today and describes their structure, pharmacokinetics, pharmacodynamics, efficacy, and safety. Continue reading >>

Two Types Of Insulin: Human And Analog

Two Types Of Insulin: Human And Analog

Glucose is a type of sugar from food that the body uses for energy. The level of glucose in the bloodstream usually rises after a meal. To be efficiently utilized by the body, glucose in the bloodstream needs to enter the body’s cells. If glucose is unable to enter the cells, blood glucose levels rise leading to hyperglycemia. Long-term hyperglycemia damages nerves, blood vessels and vital organs. Insulin is a hormone produced by the beta cells of the pancreas. The beta cells release more insulin whenever there is a rise in blood glucose levels. Insulin enables glucose to enter the cells, thereby restoring normal blood glucose levels and allowing efficient glucose metabolism. People with type 1 diabetes can no longer produce insulin because the disease has destroyed the beta cells of their pancreas. People with type 2 diabetes can produce insulin but their body does not respond well to it, a condition known as insulin resistance. Insulin resistance also develops in pregnant women with gestational diabetes because the placenta (organ that connects the fetus to the mother’s blood supply) produces insulin-blocking hormones. Insulin therapy replaces or supplements the body’s own insulin, thereby restoring normal or near-normal blood sugar levels. It is one of the cornerstones of diabetes management, providing intensive blood glucose control crucial in preventing diabetes-related complications. Why is insulin injected into the fat under the skin rather than taken as a pill? Because insulin taken in pill form would be broken down by digestive enzymes and rendered ineffective. The first generation of man-made insulin is called “human insulin.” Developed through the 1960s and 1970s and approved for pharmaceutical use in 1982, human insulin is the name given to synthet Continue reading >>

Evidence For The Use Of Short-acting Insulin Analogues

Evidence For The Use Of Short-acting Insulin Analogues

Evidence for the use of insulin analogues In the last two decades, insulin analogues have gained widespread popularity, with most patients in the Western world using short-acting analogues rather than human (regular) insulin, and long-acting analogues driving out NPH insulin. While there are definitely some circumstances in which the insulin analogues may offer a benefit, many patients will do very well with the cheaper conventional insulins. Thus, the decision to start insulin analogues in an individual patient should be taken only when the conventional insulins have been proven inadequate. The short-acting insulin analogues are known for their more rapid absorption after subcutaneous injection, resulting in an earlier insulin peak and a shorter duration of action compared to human regular insulin. This is generally thought to translate into three clinical benefits: the ability to inject the insulin-analogue just before the meal lower postprandial glucose excursions a reduced the risk of (nocturnal) hypoglycaemia As for the first point, it is true that the more rapid onset of action allows for a shorter time-interval between injection and meal. It has been shown that the instruction to inject regular insulin more than 20 minutes before a meal is widely disregarded, and a shorter time interval between injection and meal is appreciated by patients. It should however be noted that many factors influence the pharmacokinetics of insulin absorption. Thus, it was demonstrated that in obese patients (with a thick subcutaneous fat layer) the absorption of s.c. injected insulin and insulin analogues is clearly slowed down, so that earlier injection may still be necessary, and the benefits of the short-acting insulin analogues may not materialize in all of these patients. As for Continue reading >>

Analogue Insulin

Analogue Insulin

Tweet Analogue insulin is a sub-group of human insulin. Analogue insulin is laboratory grown but genetically altered to create either a more rapid acting or more uniformly acting form of the insulin. This can have advantages for blood sugar management. Analogue insulins have been available since just before the start of the new millennium. How is human analogue insulin produced? Similar to human insulin, analogue insulin is laboratory created by growing insulin proteins within E-coli bacteria (Escherichia coli). The process goes further through changing the order of amino acids to allow the insulin to be used by the body either more rapidly or more uniformly by the body than with regular human insulin. This type of process is known as undergoing ‘recombinant DNA’ technology. What types of analogue insulin are available? Analogue insulin is available in two main forms, rapid acting and long acting, as well as premixed combinations. Examples of analogue insulin: Rapid acting: Humalog, NovoRapid Long acting: Lantus, Levemir, Tresiba Premixed analogue insulins: Humalog Mix 25, Humalog Mix 50, NovoMix 30 Tweet Type 2 diabetes mellitus is a metabolic disorder that results in hyperglycemia (high blood glucose levels) due to the body: Being ineffective at using the insulin it has produced; also known as insulin resistance and/or Being unable to produce enough insulin Type 2 diabetes is characterised by the body being unable to metabolise glucose (a simple sugar). This leads to high levels of blood glucose which over time may damage the organs of the body. From this, it can be understood that for someone with diabetes something that is food for ordinary people can become a sort of metabolic poison. This is why people with diabetes are advised to avoid sources of dietary suga Continue reading >>

Degludec: The New Ultra-long Insulin Analogue

Degludec: The New Ultra-long Insulin Analogue

Abstract The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, “De”) and the attachment, via a glutamic acid linker (“glu”), of a 16-carbon fatty diacid (hexadecanoic diacid, “dec”) to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26–52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia. Introduction In spite of the body of evidence demonstrating the importance of tight glycemic control in the prevention of chronic complications of diabetes mellitus (DM), achieving the targets recommended by the Diabetes Societies’ Guidelines remains a difficult task. Among Continue reading >>

The Use Of Premixed Insulin Analogues In The Treatment Of Patients With Type 2 Diabetes Mellitus: Advantages And Limitations

The Use Of Premixed Insulin Analogues In The Treatment Of Patients With Type 2 Diabetes Mellitus: Advantages And Limitations

Abstract Background: Intensive, target-oriented therapy is the standard of care in the management of patients with type 2 diabetesmellitus (DM). Early and aggressive use of insulin that is as close as possible to the physiologic pattern of insulin secretion from healthy pancreatic β-cells is advocated to achieve glycemic goals and reduce complications of DM. Objective: The objective of this article was to review the characteristics, advantages, and drawbacks of premixedinsulin analogues and to evaluate their role in the treatment of patients with type 2 DM. Methods: A PubMed search of articles from 1990 to 2006 was undertaken using the search terms type 2 diabetes, basalbolus therapy, premixed insulins, biphasic insulins, and insulin analogues. Pertinent content from relevant articles was extracted and combined with the authors' knowledge, experience, and clinical expertise. Results: The advent of insulin analogues has streamlined the treatment of patients with DM. When to initiate insulin during the course of treatment is the subject of much debate. Insulin therapy targeting both fasting and postprandial hyperglycemia is important in achieving optimal blood glucose (BG) control in patients with type 2 DM. A practical and feasible option is the use of >1 injection of premixed insulin analogues. Premixed insulin preparations provide both basal and prandial coverage because of their biphasic pharmacokinetic properties. Clinical trials have shown that these agents improve glycemic control, are associated with an acceptably low rate of severe hypoglycemia, and have a high degree of patient acceptance. Limitations include the inability to adjust the long- and short-acting components separately, to use a flexible regimen of self-titration and premeal bolus-insulin calculatio Continue reading >>

Pharmacokinetic And Pharmacodynamic Advantages Of Insulin Analogues And Premixed Insulin Analogues Over Human Insulins: Impact On Efficacy And Safety.

Pharmacokinetic And Pharmacodynamic Advantages Of Insulin Analogues And Premixed Insulin Analogues Over Human Insulins: Impact On Efficacy And Safety.

Abstract Human insulin preparations administered to patients with diabetes mellitus fail to reproduce the normal physiologic pattern of insulin secretion. Modifications have been made in the amino acid sequence of the insulin molecule with the aim of overcoming the pharmacokinetic shortcomings of human insulins. Such modifications have produced long-acting analogues, with relatively flat time-action profiles, for controlling glycemic levels between meals; and rapid-acting analogues with a fast onset and short duration of action, for controlling postprandial hyperglycemia. Premixed formulations of the rapid-acting analogues, containing both rapid-acting soluble and intermediate-acting protaminated forms, are also available. Trials of long-acting insulin analogues have consistently shown efficacy in controlling fasting plasma glucose and glycosylated hemoglobin (HbA1c), as well as a markedly reduced risk of hypoglycemia compared with neutral protamine Hagedorn insulin. The rapid-acting and premixed analogues offer better control of postprandial glucose excursions than do regular human insulin, resulting in similar or lower HbA1c levels. Furthermore, the analogues can offer patients greater flexibility and more convenience in administration compared with human insulins. This review provides an overview of the insulin analogues available today and describes their structure, pharmacokinetics, pharmacodynamics, efficacy, and safety. Continue reading >>

Insulin Analogues In Children And Teens With Type 1 Diabetes: Advantages And Caveats

Insulin Analogues In Children And Teens With Type 1 Diabetes: Advantages And Caveats

This article reviews the advantages to and caveats of the use of newer insulin formulations (insulin analogues) and regimens in children and teens who have type 1 diabetes, their affect on glycemic control, frequency of hypoglycemic events, daily insulin requirements, and adverse affects such as excessive weight gain, which provides a further major challenge in adolescents. We also address briefly the use of adjunctive agents in the treatment of type 1 diabetes in children and teens. To access this article, please choose from the options below Continue reading >>

Therapeutics Of Diabetes Mellitus: Focus On Insulin Analogues And Insulin Pumps

Therapeutics Of Diabetes Mellitus: Focus On Insulin Analogues And Insulin Pumps

Copyright © 2010 Vasiliki Valla. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients. 1. Int Continue reading >>

Insulin Aspart Revisited: New And Clinical Differential Aspects Versus Other Rapid-acting Insulin Analogs

Insulin Aspart Revisited: New And Clinical Differential Aspects Versus Other Rapid-acting Insulin Analogs

Review *Correspondence: Francisco Javier Ampudia-Blasco [email protected] †These authors contributed equally to this work. 1. Diabetes Reference Unit, Endocrinology and Nutrition Department, Clinic University Hospital of Valencia and Department of Medicine, University of Valencia, Valencia, Spain. © 2013 Ampudia-Blasco et al; licensee Herbert Publications Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The gradual deterioration of the pancreatic β-cell function in type 2 diabetes mellitus (T2DM) patients prompts the progressive introduction of more complex treatments, including the initiation of insulin in many patients. Rapid-acting insulin analogs (aspart, lispro, and glulisine) show advantages over human regular insulin due to their rapid absorption, short duration, and higher maximum insulin peaks. We reviewed the differential aspects of insulin aspart, its potential role in various strategies for intensifying insulin treatment in T2DM and its use in special situations such as older patients, pregnant women with diabetes, and treatment of hyperglycemic crises. keywords: Type 2 diabetes mellitus, hyperglycemia, rapid-acting insulin analogs, aspart, basal-bolus therapy, stepwise therapy Introduction Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), remains an important public health problem given its worldwide prevalence and the associated morbidity and mortality. Progressive deterioration of pancreatic β-cell function over time necessitates initiation of insulin treatment in a significant proportion of patients with T2DM for achieving or maintaining g Continue reading >>

Insulin Analogs—are They Worth It? Yes!

Insulin Analogs—are They Worth It? Yes!

The availability of insulin analogs has offered insulin replacement strategies that are proposed to more closely mimic normal human physiology. Specifically, there are a considerable number of reports demonstrating that prandial insulin analogs (lispro, aspart, glulisine) have pharmacokinetic and pharmacodynamic profiles closer to normal, with resulting faster onset and offset of insulin effect when compared with regular human insulin. In addition, basal insulin analogs (glargine, detemir) have been reported to offer longer duration of action, less variability, more predictability, less hypoglycemia (especially nocturnal), and a favorable effect on weight. However, an argument against use of analog insulins as compared with use of regular or NPH insulin is one that states that the effectiveness and risk of hypoglycemia are the only two valid clinical outcomes that should be used to compare the analog and human insulins. Thus, there remains a debate in some circles that analog insulins are no more effective than human insulins, yet at a much higher financial cost. To provide an in-depth understanding of both sides of the argument, we provide a discussion of this topic as part of this two-part point-counterpoint narrative. In the counterpoint narrative, Dr. Davidson provides his argument and defends his opinion that outside of a few exceptions, analog insulins provide no clinical benefit compared with human insulins but cost much more. In the point narrative presented here, Dr. Grunberger provides a defense of analog insulins and their value in clinical management and suggests that when evaluating the “cost” of therapy, a much more global assessment is needed. Editor in Chief, Diabetes Care Introduction Insulin analogs offer insulin replacement strategy that results i Continue reading >>

Insulin Analogs

Insulin Analogs

Insulin analogs are now replacing human insulin in the US. Insulins are categorized by differences in onset, peak, duration, concentration, and route of delivery. An analog refers to something that is “analogous” or similar to something else. Therefore, “insulin” analogs are analogs that have been designed to mimic the body’s natural pattern of insulin release. These synthetic-made insulins are called analogs of human insulin. However, they have minor structural or amino acid changes that give them special desirable characteristics when injected under the skin. Once absorbed, they act on cells like human insulin, but are absorbed from fatty tissue more predictably. In this section, you will find information about: Rapid-acting injected insulin analog The fastest-working insulins are referred to as rapid-acting insulin. They include: These insulin analogs enter the bloodstream within minutes, so it is important to inject them within 5 to 10 minutes of eating. They have a peak action period of 60-120 minutes, and fade completely after about four hours. Higher doses may last slightly longer, but will last no more than five or six hours. Rapid acting insulin analogs are ideal for bolus insulin replacement. They are given at mealtimes and for high blood sugar correction. Rapid-acting insulins are used in insulin pumps, also known as continuous subcutaneous insulin infusion (CSII) devices. When delivered through a CSII pump, the rapid-acting insulins provide the basal insulin replacement, as well as the mealtime and high blood sugar correction insulin replacement. The insulins that work for the longest period of time are referred to as long-acting insulin. They provide relatively constant insulin levels that plateau for many hours after injection. Sometimes these in Continue reading >>

Short-acting Insulin Analogues Vs. Human Insulin For Diabetes

Short-acting Insulin Analogues Vs. Human Insulin For Diabetes

Practice Pointers Six to 7 million people use insulin or insulin analogues2 in the United States. Patients with type 2 diabetes who maintain tight glucose control have fewer microvascular complications.3 There are many options for the management of insulin in patients with type 1 or type 2 diabetes mellitus. Insulin therapy consists of prandial (bolus) insulin, basal insulin, and correction-dose insulin.4 There are four main types of insulin used for glycemic control: immediate-acting, rapid-acting, intermediate-acting, and long-acting (see accompanying table). Immediate- and rapid-acting insulins are used as bolus insulins; intermediate- and long-acting insulins are used as basal insulins. Insulin type Onset (minutes) Peak (hours) Duration (hours) Immediate-acting Insulin lispro solution 15 0.5 to 1.5 2 to 5 Insulin aspart solution 15 1 to 3 3 to 5 Rapid-acting Regular 30 to 60 2 to 4 8 to 12 Prompt insulin zinc solution 60 to 90 5 to 10 12 to 16 Intermediate-acting Isophane insulin suspension NPH 60 to 150 4 to 12 24 Lente 60 to 150 7 to 15 24 Long-acting Ultralente 240 to 480 10 to 30 20 to 36 Lantus 60 5 24 or more Traditional methods of insulin therapy use neutral protamine Hagedorn (NPH) and regular insulin in combination at a ratio of 70:30 taken before morning and evening meals. NPH often is moved to bedtime with regular insulin still taken before the evening meal.2 Another option is prandial insulin with meals in addition to basal insulin once or twice per day. Insulin pumps commonly are used to give continuous subcutaneous insulin.2 One of the benefits of the newer short-acting analogues is their fast onset, which allows patients to take insulin immediately before eating instead of 30 minutes in advance. Also, they enable patients to dose insulin after eating, Continue reading >>

Insulin Analog

Insulin Analog

An insulin analog is an altered form of insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of glycemic control. Through genetic engineering of the underlying DNA, the amino acid sequence of insulin can be changed to alter its ADME (absorption, distribution, metabolism, and excretion) characteristics. Officially, the U.S. Food and Drug Administration (FDA) refers to these as "insulin receptor ligands", although they are more commonly referred to as insulin analogs. These modifications have been used to create two types of insulin analogs: those that are more readily absorbed from the injection site and therefore act faster than natural insulin injected subcutaneously, intended to supply the bolus level of insulin needed at mealtime (prandial insulin); and those that are released slowly over a period of between 8 and 24 hours, intended to supply the basal level of insulin during the day and particularly at nighttime (basal insulin). The first insulin analog approved for human therapy (insulin Lispro rDNA) was manufactured by Eli Lilly and Company. Fast acting[edit] Lispro[edit] Main article: Insulin lispro Eli Lilly and Company developed and marketed the first rapid-acting insulin analogue (insulin lispro rDNA) Humalog. It was engineered through recombinant DNA technology so that the penultimate lysine and proline residues on the C-terminal end of the B-chain were reversed. This modification did not alter the insulin receptor binding, but blocked the formation of insulin dimers and hexamers. This allowed larger amounts of active monomeric insulin to be available for postprandial (after meal) injections.[1] Aspart[edit] Main article: Insulin aspart Novo Nordisk created "aspart" and Continue reading >>

Publications

Publications

Diabetes mellitus (DM) is associated with a huge social and economic burden. Achieving guidelines glycemic targets can help reduce the burden of type 2 DM (T2DM)-related complications; however many patients fail to meet these goals. The introduction of insulin analogs, including biphasic insulin analogs, has helped to reduce barriers to patient adherence and to improve outcomes. This review examines the clinical benefits and cost utility of biphasic insulin analogs versus other treatment approaches, in particular human biphasic insulins. Biphasic insulin analogs have a greater flexibility of dosing as compared to equivalent human insulin preparations, resulting in greater convenience and patient satisfaction, and in observational studies, improved efficacy in terms of glycemic control in patients inadequately controlled on human biphasic insulin. Biphasic insulin analogs have shown improved postprandial glucose (PPG) control and a reduced risk of hypoglycemia compared with biphasic human insulin. Treatment with biphasic insulin analogs is cost-effective versus other options in the long term. Biphasic insulin analog treatment of uncontrolled T2DM should be considered an appropriate investment of healthcare resources. Introduction It is well known that diabetes mellitus (DM) is associated with a huge social and economic burden, representing the third most common reason for hospitalization (as a first-listed diagnosis) in the U.S. in 2006 and accounting for 10.6 percent of hospital discharges (1). In 2005, discharge data from patients with diabetes as a first-listed diagnosis documented approximately 2.8 million days of hospital stay, corresponding to an average length of stay of 4.7 days (1). In 2007, the costs for DM were $174 billion in the U.S., composed of $116 billio Continue reading >>

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