insulin-detemir and insulin-glulisine

Insulin remains a predominant life-saving medication for type 1 and type 2 Diabetes Mellites. Natural insulin secretion limits the fluctuation of the narrow and high surge of blood glucose levels. However, imitating the same by external insulin remains a challenge as a variety of insulin analogs (rapid acting, short acting, intermediate acting and long-acting) have different pharmacokinetic (PK) and pharmacodynamic (PD) properties. Inconsistent reduction in overall hyperglycemia level and nocturnal hypoglycemia due to variable absorption time and time action profile predominantly highlights the need of revisiting the PK/PD of insulin analogs as single analog is not yet sufficed to replace internal insulin exogenously. Combination therapy with basal and prandial insulins or intensification of hypoglycemic therapy with premixed insulins are of prime importance in managing diabetes effectively, imitating the natural insulin secretion. Therefore, the knowledge of PK/PD properties might help a practitioner to design, implement and manage insulin replacement therapy effectively and averting adverse events. Present study reports the comparative analysis of PK/PD profile of various insulin analogs based on the concurrent information about clinical aspects. Moreover, study interlinks the major concerns of therapeutic efficacy of insulin analogs with their respective onset of action and duration of effectiveness and reported adverse drug reaction which explore the scope of improvement.

Topics: Diabetes Mellitus; Forecasting; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Insulin allergy is a rare yet severe side effect of exogenous insulin use. Management typically involves use of alternative antihyperglycaemic agents, symptom control with antihistamines, use of different insulin formulations, and induction of tolerance with incremental doses of insulin. This treatment regimen is not always successful, and the use of omalizumab, an anti-IgE monoclonal antibody, has been used to induce tolerance to insulin.. G.M. is a 62-year-old man with Type 2 diabetes mellitus. His condition was not optimized on oral agents, and insulin therapy was required. G.M. had anaphylaxis to insulin NPH, and subsequent skin-prick testing was positive to insulin aspart, insulin NPH, insulin glulisine, insulin detemir, regular insulin, insulin glargine 100 units/ml and insulin glargine 300 units/ml. He received incremental doses of several insulin formulations; however, he experienced diffuse urticaria preventing optimal glycaemic control. Three successful cases have been described in the literature of omalizumab inducing tolerance to exogenous insulin; therefore, G.M. was started on omalizumab. He subsequently tolerated treatment doses of insulin glulisine and insulin detemir with no allergic reactions and with improvement in glycaemic control.. To our knowledge, this is the first described case of allergy to insulin glargine 300 units/ml and reiterates the potential use of omalizumab in insulin allergy. Further research is warranted to determine if omalizumab should be considered standard of care in difficult-to-treat insulin hypersensitivity.

Topics: Anaphylaxis; Anti-Allergic Agents; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Omalizumab

Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes. The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy. Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycaemic control in women with type 1 diabetes. However, a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short-acting analogue where the woman's diabetes is well controlled with human insulin. There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended. Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes. There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control. A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia. The greater evidence base supports the use of insulin detemir as the first line long-acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin. There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Randomized Controlled Trials as Topic; Treatment Outcome

Since insulin is the unique and life-long therapy in type 1 diabetes and classical insulin preparations have certain limitations due to their pharmacokinetic and pharmacodynamic properties, the new insulin analogues aim to eliminate these limitations. Five insulin analogues are commercially available and approved for individuals with type 1 diabetes: three rapid-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting insulin analogues (insulin glargine and insulin detemir). According to several studies conducted in children with type 1 diabetes, insulin analogues, due to their structural alterations, offer flexibility, reduction of nocturnal hypoglycemic episodes and decrease in postprandial hyperglycemic events, resulting in improved quality of life for diabetic children and their families. However, diabetes control measured with glycosylated hemoglobin A1c has been reported to be similar to conventional insulin preparations. Evidence-based medical reports indicate that insulin analogues are safe and effective, and therefore approved for children even from the age of 2 years. Moreover, suspicions and reports on the association of insulin analogues with carcinogenesis have not been established, requiring further investigation. This review reports the properties and characteristics of insulin analogues, as well as the results of current studies concerning pediatric patients with type 1 diabetes.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles and provide better postprandial glucose control and less hypoglycaemia (primarily nocturnal and severe hypoglycaemia in type 1 diabetes mellitus) than regular insulin. Insulin glulisine is a new rapid-acting analogue and has characteristics nearly identical to those of its predecessors. Insulin glargine was the first basal analogue approved for clinical use and has shown better fasting glucose control and less risk of hypoglycaemia than conventional human neutral protamine Hagedorn (NPH) insulin. More recent studies have indicated that insulin glargine may not be truly 'peakless' at higher doses and that the adjustment of dose timing and frequency may have favourable effects on the risk of hypoglycaemia and the duration of the effect. Insulin detemir is a new basal insulin analogue with superiority to NPH insulin similar to that demonstrated by insulin glargine, though its duration of action appears to be shorter. The intraindividual variability in the response to a given dose is lower for insulin detemir than for both NPH insulin and insulin glargine. The clinical significance of this finding is not clear, though it may contribute to the lower rate of hypoglycaemia seen with insulin detemir. A number of 'alternative routes' of insulin administration have been studied, the most promising of which has been the pulmonary route. The time-action profile of inhaled insulins is generally characterized by a rapid onset of action similar to those of rapid-acting analogues and a slightly protracted duration of action similar to that of regular insulin. Inhaled insulin is similar to regular insulin with respect to efficacy and safety, though small reversible changes in pulmonary function have been noted. For technical and practical reasons, other alternative routes have generally not met with clinical success.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus; Drug Administration Routes; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

A recent meta-analysis evaluated trials of the rapid-acting analogues insulin lispro and insulin aspart, performed before the introduction of the basal analogues, insulin glargine and insulin detemir. This article reviews the effect of rapid-acting and basal insulin analogues separately and in combination, relative to human insulin. Outcomes evaluated include HbA(1c), hypoglycaemia, postprandial glucose (PPG), and weight changes. Results from trials that matched defined criteria are presented in tables. In type 1 diabetes, compared with human insulin, the rapid-acting analogues generally reduced hypoglycaemia and postprandial glucose, whereas the basal analogues tended to reduce hypoglycaemia -- particularly nocturnal hypoglycaemia. Weight gain may also be reduced with basal analogues, compared with human basal insulin. In type 2 diabetes, premix rapid-acting analogues controlled postprandial glucose better than human insulin mixes; basal analogues used as basal-only therapy reduced hypoglycaemia compared with NPH insulin; and some advantages were apparent with analogues in basal-bolus therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapid-acting analogues and the potential for reduction in cardiovascular risk, should be investigated further.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period; Randomized Controlled Trials as Topic

This review reports the literature on the safety and efficacy of insulin analogues in pregnancy and thereby enables the clinician to choose the optimal insulin treatment protocol to achieve and maintain normoglycemia throughout pregnancies complicated by diabetes. This article also reviews the literature on the insulin analog during pregnancy and presents the authors' opinion as to the safety and efficacy of insulin analog treatment for the pregnant diabetic woman.

Topics: Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Receptor, IGF Type 1

Insulin analogues, developed by molecular engineering, have structural changes in the A and B insulin chains. These modifications change their action profile, rendering insulin replacement closer to physiology. Rapid acting analogues like lispro, aspart and glulisine, are absorbed rapidly from the subcutaneous tissue to the circulation. In addition, two long acting insulin analogues have been developed: glargine and detemir. The combination of a long acting insulin, to maintain baseline levels, and multiple daily doses of a rapid acting analogue are the mainstay of basal-bolus therapy. Multiples studies have compared human insulin (NPH and regular) with insulin analogues in patients with type 1 or 2 diabetes mellitus, showing an improvement in the metabolic control, fewer hypoglycemic events and better quality of life. In summary, insulin analogues offer new therapeutic options and allow an individualized intensive treatment.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Lispro; Insulin Secretion; Insulin, Long-Acting

Achieving and maintaining glycemic control (glycated hemoglobin--HbA(1c)< or =7.0% according to American Diabetes Association and < or =6.5% according to International Diabetes Federation) is the primary goal in treating diabetes, which lowers the risk for diabetes-related complications. Insulin therapy is essential for type 1 diabetes treatment. Insulin therapy in type 2 diabetes is initiated when glycemic control is inadequate despite the combination of antihyperglycemic drugs. The type of insulin therapy is selected according to the patient's lifestyle and needs. Multiple insulin injection therapy and premixed insulin therapy are usually administered. In multiple insulin injection therapy, basal insulin is administered one or two times a day, and regular human insulin or rapid-acting insulin analog is administered with each meal. The duration of action of regular insulin is 6-8 hours; therefore, the risk for postprandial hypoglycemia is increased. The action of novel insulin analogs (rapid- and long-acting) closely mimics physiological insulin secretion. Three rapid-acting insulin analogs are currently available: insulin lispro, insulin aspart, and insulin glulisine. Insulin glulisine is the most recently approved rapid-acting insulin analog. It is safe, flexible, and effective in achieving target postprandial glycemic control. Moreover, the pharmacokinetics of insulin glulisine does not depend on the amount of subcutaneous fat. Basal insulins include intermediate-acting human insulins (neutral protamine Hagedorn) and long-acting insulin analogs (insulin glargine, insulin detemir). The latter are the optimal choice covering basal insulin requirement. Compared to neutral protamine Hagedorn insulin, long-acting insulin analogs have no pronounced concentration peak and reduce nocturnal hypoglycemia risk and weight gain.

Topics: Adolescent; Adult; Age Factors; Aged; Algorithms; Blood Glucose; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Life Style; Middle Aged; Risk Factors; Time Factors

Topics: Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Direct qualitative methods that allow the rapid screening and identification of insulin products during early stages of the drug development process and those already in the market can be of great utility for manufacturers and regulatory agencies and the recent scientific literature describes several methods. Herein, a qualitative proteomic method is presented for the identification of recombinant human insulin and all marketed biosynthetic analogues -insulin lispro, aspart, glulisine, glargine, detemir and degludec- via tryptic digestion and identification of proteotypic peptides for each insulin. Individual insulins were first denatured under reducing conditions and the cysteine residues blocked by iodoacetamide. The proteins were then digested with trypsin and the peptide products separated by reversed phase liquid chromatography on an Ascentis® Express ES-C18 column and detected by positive polarity ESI-MS/MS. The digestion peptides were characterized using a multiplexed MRM approach that monitors the fragmentation of the doubly charged unlabeled precursor ion of each peptide into a collection of signature y and b ions. The MRM transitions for the individual peptides were optimized to allow maximal ionization on a standard triple quadrupole mass spectrometer. All products of the digestion procedure for all insulins were detected with adequate signal intensity except for the C-terminal B30Thr whenever it was present and cleaved and the tryptic B1-3 tripeptide of insulin glulisine. The unique proteotypic peptides identified for each of the insulin analogues coupled with their signature y and b ions permitted the unambiguous verification of all sequence variations and chemical modifications. The elution of the A polypeptide chain for all insulins and the tryptic peptides of the B chain, with the exception of a very few, occurred around the same time point. This underscores the close similarity in the physicochemical properties between the digestion peptides and is consistent with the subtle variations in amino acid sequence among the various insulins. Therefore, the identification and distinction of the different types of insulin based solely on the chromatographic retention time of their respective proteolytic products can be deceptive without proper mass spectrometric analysis and may result in false positives.

Topics: Amino Acid Sequence; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Peptide Fragments; Peptides; Proteolysis; Proteomics; Tandem Mass Spectrometry

Several studies suggest benefits of insulin analogues detemir or glulisine in overweight and obese patients with type 2 diabetes. The present multicentre study therefore examines, whether these insulin analogues are used more frequently in patients with increased body mass index.. Data of 38 560 adult type 2 diabetic patients using insulin analogues, from 150 centres in Germany, registered in a standardized, prospective, computer-based documentation program (DPV), were included. Patients were classified into body mass index categories according to World Health Organization. Analysis was stratified by 3 time periods. To adjust for confounding effects, multivariable logistic regression models were created.. Detemir was preferentially used in overweight (OR 1.36, 95%-CI 1.20-1.53) and obese patients (OR 2.06, 95%-CI 1.84-2.31) compared to normal-weight patients. These effects remained significant after adjusting for sex, age, new/old federal state of Germany, size of centre, treatment in university clinic and clinic/specialized private practice. Models were additionally adjusted for time period and interaction of BMI category with age or sex. For glulisine, a minor effect was present when comparing obese to normal-weight patients (OR 1.26, 95%-CI 1.06-1.50). After adjustment, this finding was no longer significant. Stratified by obesity grade, class III obese patients more frequently used detemir or glulisine compared to class I obese patients. Comparing time periods, odds ratios did not differ, neither for detemir nor for glulisine..  Detemir is used more often in overweight and obese patients compared to normal-weight patients. For glulisine, the relationship is less pronounced.

Topics: Aged; Body Weight; Databases, Factual; Diabetes Mellitus, Type 2; Drug Prescriptions; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Obesity; Overweight; Practice Patterns, Physicians'; Registries

In this article, you'll learn about 13 new drugs, including: insulin glulisine and insulin detemir, both human insulin analogues; ranolazine, the first drug approved to treat chronic angina in more than a decade; conivaptan HCl, the first drug approved to treat hyponatremia in patients with normal fluid balance. Unless otherwise specified, the information in the following summaries applies to adults, not children. Consult the package insert for information about each drug's safety during pregnancy and breast-feeding. Also consult the package insert, a pharmacist, or a comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions for all these drugs.

Topics: Abatacept; Acetanilides; Alprostadil; Anidulafungin; Antidiuretic Hormone Receptor Antagonists; Antifungal Agents; Antineoplastic Agents; Arabinonucleosides; Benzazepines; Benzenesulfonates; Drug Approval; Drug Interactions; Drug Monitoring; Drug Therapy; Echinocandins; Fatty Acids; Humans; Hypoglycemic Agents; Immunoconjugates; Immunosuppressive Agents; Indoles; Insulin; Insulin Detemir; Insulin, Long-Acting; Intercellular Signaling Peptides and Proteins; Lenalidomide; Lubiprostone; Niacinamide; Patient Education as Topic; Peptides, Cyclic; Phenylurea Compounds; Piperazines; Pyridines; Pyrroles; Ranolazine; Sorafenib; Sunitinib; Thalidomide; United States