المؤلفون: Emily G. Moser, Satish K. Garg, Megha Dhingra, Aaron Blau, Viral N. Shah

المصدر: Diabetes Technology & Therapeutics. 15:727-732

مصطلحات موضوعية: medicine.medical_specialty, Swine, Ultralente, Chemistry, Pharmaceutical, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin, Isophane, Insulin Glargine, Insulin analog, Protamine zinc insulin, NPH insulin, Dogs, Insulin Infusion Systems, Endocrinology, Insulin resistance, Insulin Detemir, Internal medicine, Diabetes Mellitus, Animals, Humans, Hypoglycemic Agents, Insulin, Medicine, Biosimilar Pharmaceuticals, Insulin detemir, business.industry, Insulin glargine, History, 20th Century, medicine.disease, Insulin, Long-Acting, Medical Laboratory Technology, Delayed-Action Preparations, business, medicine.drug

الوصف: Diabetes has been known to mankind for hundreds of years and was considered a deadly disease before the advent of insulin. It was the discovery of insulin by Frederick Banting and Charles Best that revolutionized the management of diabetes. Early insulins were made from either bovine or porcine whole pancreata. These early insulins were rather crude and impure. Because they differ by two or three amino acids from human insulin, immunologic reactions resulted such as insulin allergy, immune-mediated lipoatrophy at the injection site, antibody-mediated insulin resistance, and significant hyperglycemia and hypoglycemia due to unpredictable dissociation of insulin from antibodies. The initial insulins including bovine and porcine insulins were short-acting, and therefore it was difficult for patients to take several injections per day. Patients were often unable to optimize glucose control because of difficulty in adjusting the frequent doses of insulin needed to achieve euglycemia without hypoglycemia. Over a period of time, we understood that, physiologically, there is a continuous small amount of insulin secretion from the b-cells in the pancreas called basal insulin. Therefore, it became necessary to look for a more pure and ideal insulin that had a duration of action of at least 24 h. The early development of insulin diverged in two directions; many researchers were working on the purification of existing insulins, while others were working on longeracting insulins. It was Sanger’s discovery of insulin’s amino acid sequence in 1950 that paved the way to manufacturing of human insulin. The task of manufacturing insulin on a larger scale was made possible with the use of recombinant technology in the 1970s. Currently available insulins are recombinant DNA-derived human insulins. Bovine and porcine insulins are no longer available worldwide. During the same time frame, researchers were working on prolonging the duration of insulin action, resulting in the development of the first long-acting insulin analog (LAIA) known as protamine zinc insulin in the 1930s. Use of protamine zinc insulin was limited by the great risk of sudden hypoglycemia, slow onset of action, and high interand intraindividual variability. Soon after, in 1946, Hans Hagedorn and colleagues introduced crystalline neutral protamine Hagedorn (NPH) insulin, which was a more stable protamine zinc insulin. This modification combined insulin and protamine in ‘‘isophane’’ proportions (no excess of insulin or protamine) at neutral pH in the presence of a small amount of zinc and phenol and/or phenol derivatives to form a tetragonal oblong-shaped hexamer. During the same time in 1950, Hallas-Moller developed the lente insulins: lente, semilente, and ultralente, of which ultralente was the longer-acting insulin. These long-acting insulins (NPH and ultralente) came on the market and quickly gained widespread popularity among physicians in the 1940s and 1950s. However, these LAIAs were still not ideal. The NPH insulin exhibited a highly variable absorption profile (especially if not properly mixed before injection) and had a peak action of approximately 6 h, resulting in poor glycemic control and unpredictable hypoglycemia, especially nocturnal.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1798cb036f30f35084e7337f81304aa0Test
https://doi.org/10.1089/dia.2013.0228Test

المؤلفون: Katarzyna Kolasa, Cezary Sciborski, Phil McEwan, Leszek Czupryniak, Isabelle Duprat Lomon, Władysław Grzeszczak

المصدر: Diabetes Technology & Therapeutics. 14:65-73

مصطلحات موضوعية: Male, medicine.medical_specialty, Cost effectiveness, Cost-Benefit Analysis, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin, Isophane, Adamantane, NPH insulin, Type 2 diabetes, Saxagliptin, chemistry.chemical_compound, Endocrinology, Diabetes mellitus, Internal medicine, medicine, Humans, Hypoglycemic Agents, Glycated Hemoglobin, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Insulin, Type 2 Diabetes Mellitus, Dipeptides, Middle Aged, medicine.disease, Metformin, Medical Laboratory Technology, Models, Economic, Sulfonylurea Compounds, Diabetes Mellitus, Type 2, chemistry, Drug Therapy, Combination, Female, Poland, Quality-Adjusted Life Years, business, medicine.drug

الوصف: This study compared the health and economic benefits of saxagliptin versus insulin as second-line therapy with either metformin (MET) or sulfonylurea (SU) after failure of the respective monotherapies for patients with type 2 diabetes in Poland.The cost-effectiveness was assessed using a previously published diabetes model. Disease progression, utilities, and effects of changes in glycosylated hemoglobin (HbA1c), weight, and hypoglycemic events were taken from published studies, and Polish sources were used where possible.MET + saxagliptin reduced severe hypoglycemic complications and weight versus MET + insulin, with an incremental benefit of 0.13 quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) of 27,454 Polish zloty (PLN) ($9,966 U.S.) per QALY gained. SU + saxagliptin showed an incremental benefit of 0.14 QALYs and ICER of 24,663 PLN ($8,953 U.S.) per QALY gained versus SU + insulin, with reduced incidence of symptomatic and severe hypoglycemias. Results were most sensitive to disutilities associated with weight gain, hypoglycemia, injection fear, HbA1c changes, threshold for switching treatment, and patients' age. Results were robust to various model assumptions and inputs. Using a willingness-to-pay threshold of 100,000 PLN ($36,300 U.S.) per QALY gained, the probability that saxagliptin is cost-effective in these analyses was 74% (MET) and 76% (SU).Saxagliptin in combination with MET or SU is likely to represent a cost-effective treatment option in Polish patients with type 2 diabetes failing first-line treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2aabf8fda99080d04d76581547510f69Test
https://doi.org/10.1089/dia.2011.0092Test

المؤلفون: Marie-Paule Dain, Emily G. Moser, Anastasia Rodionova, Satish K. Garg

المصدر: Diabetes Technology & Therapeutics. 12:835-846

مصطلحات موضوعية: Adult, medicine.medical_specialty, Adolescent, Injections, Subcutaneous, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Reviews, Insulin Glargine, Insulin analog, NPH insulin, Hypoglycemia, Infusions, Subcutaneous, Endocrinology, Internal medicine, Diabetes mellitus, Humans, Hypoglycemic Agents, Insulin, Medicine, Child, Intensive care medicine, Randomized Controlled Trials as Topic, Glycemic, Type 1 diabetes, business.industry, Insulin glargine, medicine.disease, Insulin, Long-Acting, Drug Combinations, Medical Laboratory Technology, Diabetes Mellitus, Type 1, Patient Satisfaction, business, medicine.drug

الوصف: The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia with intensive versus conventional therapy. Insulin analogs were developed to aid patients in achieving better diabetes control by providing insulins with optimized pharmacokinetic and pharmacodynamic characteristics. Insulin glargine was the first long-acting insulin analog with a 24-h duration of action, offering once-daily injection, and has now been in clinical use for over 10 years. The authors performed a systematic search of EMBASE, MEDLINE, and Web of Science (Science Citation Index) to determine the efficacy of insulin glargine in type 1 diabetes in basal-bolus insulin regimens. Randomized controlled trials have demonstrated that glycemic control with insulin glargine is at least comparable to that with neutral protamine Hagedorn (NPH) insulin in adults and in children and adolescents, and with continuous subcutaneous insulin infusion in adults. However, these same trials show a significantly lower risk for hypoglycemia with insulin glargine compared with NPH insulin in adults.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::276e1cac1a335f5880a06f340a960fbbTest
https://doi.org/10.1089/dia.2010.0135Test

المؤلفون: Ranjit Mohan Anjana, Chidambarann Sudhakaran, Maryam Fathima, Viswanathan Mohan, Ranjit Unnikrishnan I

المصدر: Diabetes Technology & Therapeutics. 12:613-618

مصطلحات موضوعية: Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Insulin, Isophane, India, Insulin Glargine, NPH insulin, Hypoglycemia, chemistry.chemical_compound, Endocrinology, Asian People, Surveys and Questionnaires, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Aged, Glycemic, Glycated Hemoglobin, Venoms, Insulin glargine, business.industry, Body Weight, Type 2 Diabetes Mellitus, Middle Aged, medicine.disease, Insulin, Long-Acting, Medical Laboratory Technology, Treatment Outcome, Diabetes Mellitus, Type 2, chemistry, Exenatide, Female, Glycated hemoglobin, Peptides, business, medicine.drug

الوصف: This study reports on the effectiveness of exenatide compared to insulin glargine or NPH insulin in patients with type 2 diabetes mellitus, unable to achieve glycemic control with oral glucose-lowering therapies in a clinical care setting.Patients with type 2 diabetes mellitus (n = 47) whose glycemia was not controlled adequately with oral hypoglycemic agents at maximum recommended therapeutic doses were initiated on exenatide therapy. Age-, sex-, and body mass index-matched patients receiving insulin glargine (n = 54) or NPH insulin (n = 23) served as controls. Data analysis included glycated hemoglobin, fasting and postprandial plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia.A statistically significant reduction in glycated hemoglobin value was noted after initiating exenatide (pre-exenatide 9.7 +/- 1.4% vs. post-exenatide 8.7 +/- 1.5%; P0.05), which was comparable to values after insulin glargine (9.8 +/- 1.1% vs. 9.0 +/- 1.5%, respectively; P0.05) and NPH insulin (9.6 +/- 1.4% vs. 8.9 +/- 1.3%, respectively; P0.05). Exenatide therapy was associated with net weight loss (mean, 1.6 kg), but therapy with insulin glargine and NPH insulin was associated with weight gain (1.8 and 2.3 kg, respectively).In a group of select Asian Indian type 2 diabetes patients with secondary failure to oral hypoglycemic agents seen at a diabetes center, exenatide treatment in combination with oral drug regimens resulted in significant lowering of glycated hemoglobin similar to insulin glargine or NPH insulin but with the additional benefit of weight loss, albeit a small amount.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd897108b0108c895874f19cfd3cb65bTest
https://doi.org/10.1089/dia.2010.0033Test

المؤلفون: David R. Owens, Geremia B. Bolli

المصدر: Diabetes Technology & Therapeutics. 10:333-349

مصطلحات موضوعية: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Molecular Sequence Data, Insulin, Isophane, Insulin Glargine, NPH insulin, Type 2 diabetes, Endocrinology, Insulin Detemir, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Glucose homeostasis, Amino Acid Sequence, Insulin detemir, Insulin glargine, business.industry, medicine.disease, Insulin, Long-Acting, Medical Laboratory Technology, Basal (medicine), business, medicine.drug

الوصف: The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a durationor=24 h, (2) a single subcutaneous dose of glargine/detemir was used, and (3) area under the curve for insulin concentrations or glucose infusion rates were calculated.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::905a2f14397936f322f2277fa3c0cb04Test
https://doi.org/10.1089/dia.2008.0023Test

المؤلفون: Reinhard H.A. Becker, Geremia B. Bolli, John E. Gerich, Ray Zhu

المصدر: Diabetes Technology & Therapeutics. 8:237-243

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Adolescent, Ultralente, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin, Isophane, Insulin Glargine, NPH insulin, Hypoglycemia, law.invention, Endocrinology, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Insulin lispro, Randomized Controlled Trials as Topic, Insulin Lispro, Clinical Trials, Phase I as Topic, Insulin glargine, business.industry, Middle Aged, medicine.disease, Insulin, Long-Acting, Medical Laboratory Technology, Diabetes Mellitus, Type 1, Female, business, medicine.drug

الوصف: The large fluctuations in blood concentrations and activity observed with insulin therapies such as NPH insulin or insulin ultralente may result in hyper- or hypoglycemia.We compared the fluctuations of these insulins with the long-acting basal insulin analog insulin glargine as a re-analysis of three Phase I studies: (I) glargine with NPH or ultralente [single-dose (0.4 IU/kg), randomized study in healthy volunteers (n = 36)]; (II) glargine or NPH [single-dose (0.3 IU/kg), randomized study in patients with diabetes mellitus Type 1 (DMT1) (n = 20)]; and (III) glargine (tailor-made dose) plus insulin lispro in DMT1 (n = 15 over 11 days). Percent deviation around average serum concentration over 24 h (PF24) was used to determine within-patient fluctuation and mean fluctuation value for each treatment group.Mean PF24 in healthy volunteers (Study I) was significantly lower with glargine (19.8%) than with NPH and ultralente (31.9% and 47.2%, respectively; both P0.001 vs. glargine). Similarly, about half the fluctuation observed with NPH (PF24 25.8%) was seen with glargine (PF24 14.2%; P0.001) in DMT1 (Study II). In ambulatory DMT1 patients receiving multiple glargine doses, PF24 values demonstrated that the same low fluctuations (PF24 20%) were retained throughout near-maintenance treatment (Study III).Glargine provided less diurnal fluctuation in serum insulin levels than NPH and ultralente in healthy volunteers and patients with DMT1. This lower fluctuation of glargine over NPH or ultralente can help to reduce hyper- or hypoglycemia risks associated with insulin therapy and accordingly encourage achievement of better blood glucose control.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::775321cae945363faf57da2829ee36bbTest
https://doi.org/10.1089/dia.2006.8.237Test

المؤلفون: Eberhard Standl, Hanne Lang, Anthony Roberts

المصدر: Diabetes Technology & Therapeutics. 6:579-588

مصطلحات موضوعية: Adult, Blood Glucose, medicine.medical_specialty, endocrine system diseases, Injections, Subcutaneous, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin, Isophane, NPH insulin, Drug Administration Schedule, law.invention, Eating, Endocrinology, Insulin Detemir, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, Humans, Hypoglycemic Agents, Insulin, Medicine, Aged, Insulin detemir, Glycemic, Glycated Hemoglobin, Type 1 diabetes, business.industry, Fasting, Middle Aged, medicine.disease, Hypoglycemia, Insulin, Long-Acting, Clinical trial, Medical Laboratory Technology, Diabetes Mellitus, Type 1, business, medicine.drug

الوصف: This trial compared the long-term safety and efficacy of the basal insulin preparations, insulin detemir and NPH insulin, in basal-bolus therapy for patients with type 1 diabetes.This multinational open, parallel-group trial randomized patients to receive insulin detemir or NPH insulin twice daily in addition to mealtime human soluble insulin. Doses were titrated towards predefined glycemic targets. After an initial 6-month treatment period, patients were invited to participate in a 6-month extension period. A total of 289 from 421 elected to continue in the trial, of which 252 completed.Glycemic control as assessed by hemoglobin A1c (insulin detemir, 7.88%; NPH insulin, 7.78%; difference not significant) and fasting plasma glucose (insulin detemir, 10.1 mmol/L; NPH insulin, 9.84 mmol/L; difference not significant) was similar in both treatment groups at end point, with hemoglobin A1c little changed from baseline and fasting plasma glucose slightly decreased. There was some evidence for a risk reduction for hypoglycemia in association with insulin detemir, although this was not statistically significant (relative risk overall hypoglycemia, 0.71, P = 0.139; relative risk nocturnal hypoglycemia, 0.71, P = 0.067), and hypoglycemic events were fewer in each of the 12 months. There was a significant treatment difference with regard to weight outcome; NPH insulin was associated with weight gain (1.4 kg), but there was no mean weight gain (-0.3 kg) in the insulin detemir cohort (baseline-adjusted between-group difference at 12 months, 1.66 kg, P = 0.002). There were no obvious between-group differences in other safety parameters.Glycemic control is maintained with insulin detemir during long-term treatment. At equivalent glycemic control to NPH insulin, insulin detemir is associated with a lack of weight gain and a trend towards a reduced risk of nocturnal hypoglycemia when used in basal-bolus therapy with mealtime soluble human insulin.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b79d9c9d6cd068c5956d8d974f9ae0eTest
https://doi.org/10.1089/dia.2004.6.579Test

المؤلفون: Ronald R. Bowsher, Daniel C. Howey, Rocco L. Brunelle, James R. Woodworth

المصدر: Diabetes Technology & Therapeutics. 6:147-153

مصطلحات موضوعية: Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, NPH insulin, Glucagon, Endocrinology, Reference Values, Internal medicine, Diabetes mellitus, Healthy volunteers, medicine, Humans, Hypoglycemic Agents, Insulin, Insulin lispro, Inhibitory effect, Insulin Lispro, business.industry, medicine.disease, Kinetics, Medical Laboratory Technology, Clamp, Glucose Clamp Technique, business, medicine.drug

الوصف: A model was established allowing prediction of blood glucose response from glucose clamp results performed in healthy volunteers. Data from published studies performed in healthy volunteers were used to establish, test, and validate a model for the evaluation of glucose reductions from glucose clamp results. Studies included those that measured blood glucose and glucodynamic response over time after administration of 0.05 U/kg of regular human insulin (HR) and insulin lispro (LP) with and without the benefit of a glucose clamp procedure. An inhibitory effect E(max) model was used to describe the relationship; the model differed between the HR and LP responses by the intensity of the counterregulatory response as assessed by glucagon measurements. The relationships were used to predict blood glucose responses from a clamp study assessing NPH insulin and HR administrations. Glucose concentrations measured after administration of NPH insulin and HR without a clamp were compared to the model-predicted results to assess the accuracy of the model predictions. The E(max) model successfully correlated the glucose clamp results with the blood glucose depressions in the presence and absence of a counterregulatory response. However, predictions of glucose depression were only accurately modeled in the absence of a counterregulatory glucagon response. The correlations established with a minimal counterregulatory response underscore the value of glucose clamp procedures in defining the time-activity profiles of insulins when the clamp is established at fasting glucose concentrations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59a092ef13cddbe7575f746b91abe0d1Test
https://doi.org/10.1089/152091504773731339Test

المؤلفون: George Dailey, Poul Strange, Matthew C. Riddle

المصدر: Diabetes Technology & Therapeutics. 11:477-479

مصطلحات موضوعية: Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Insulin, Isophane, Insulin Glargine, NPH insulin, Type 2 diabetes, Hypoglycemia, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, In patient, Intensive care medicine, Insulin glargine, business.industry, Treat to target, medicine.disease, Insulin, Long-Acting, Medical Laboratory Technology, Sulfonylurea Compounds, Diabetes Mellitus, Type 2, Glucagon Injection, business, medicine.drug

الوصف: This article reevaluates the hypoglycemic episodes reported as severe in the Treat-to-Target Trial comparing insulin glargine and NPH insulin use in patients with inadequately controlled type 2 diabetes.Case report forms from the Treat-to-Target Trial were reviewed to identify additional severe hypoglycemic events and to further characterize those events already identified. Severe hypoglycemia was defined as symptoms consistent with hypoglycemia requiring assistance of another person and associated with either glucose levelsor =56 mg/dL or prompt recovery after oral carbohydrate intake, intravenous glucose administration, or glucagon injection.This analysis confirmed that severe hypoglycemia was similarly uncommon with both insulins (insulin glargine [n = 367], nine patients, 14 events; NPH insulin [n = 389], nine patients, 13 events); all hypoglycemic events for glargine and nine for NPH were treated effectively at home. All severe hypoglycemic episodes were associated with sulfonylurea use. A review of case report forms demonstrated inconsistencies in identification of severe hypoglycemia (seven of 14 severe events for glargine and three of 13 severe events for NPH were coded as moderate).The rate of severe hypoglycemia in this trial was low. Difficulties in gathering and interpreting hypoglycemia data highlight the need for more objective methods.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f4b2446f8ec0cca8311a25e32d6075b8Test
https://doi.org/10.1089/dia.2009.0022Test

المؤلفون: Satish K. Garg, Daniel Vaughn, John B. Buse, Douglas B. Muchmore, Jay S. Skyler

المصدر: ATTD 2011 Yearbook: Advanced Technologies & Treatments for Diabetes, Third Edition

مصطلحات موضوعية: Pancreas, Artificial, Insulin degludec, medicine.medical_specialty, Biomedical Research, endocrine system diseases, medicine.medical_treatment, Endocrinology, Diabetes and Metabolism, Insulins, NPH insulin, Pharmacology, Subcutaneous injection, Endocrinology, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Animals, Humans, Hypoglycemic Agents, Insulin, Insulin lispro, New drug application, Insulin detemir, Type 1 diabetes, Insulin glargine, business.industry, digestive, oral, and skin physiology, nutritional and metabolic diseases, medicine.disease, Medical Laboratory Technology, Regimen, Postprandial, Tolerability, business, medicine.drug

الوصف: While the pharmacokinetic properties of the long-acting insulin analogues, insulin glargine and insulin detemir, clearly demonstrate clinical benefits over NPH insulin in terms of reduced frequency of overall and nocturnal hypoglycaemic events and lowered glycaemic variability, several new insulin analogues with even longer and smoother time-action profiles are being developed and explored. Among these, insulin degludec is the first to enter the market. The ultra-long action profile of this insulin analogue is mainly the result of a slow and stable release of insulin degludec monomers from soluble multihexamers that form after subcutaneous administration. In the last year, the results of the first phase II trials with insulin degludec have been published, where the efficacy and safety of this basal insulin analogue have been compared with insulin glargine in patients with type 1 (T1D) and type 2 (T2D) diabetes. With regard to short-acting insulins for mealtime insulin supplementation, there is also a search for new insulins with a more rapid onset of action, and hence improved postprandial glucose control. Linjeta (formerly named VIAject) is a human insulin formulation with faster insulin absorption and action than insulin lispro and regular human insulin. A new drug application to market Linjeta as a treatment for diabetes was submitted to the US Food and Drug Administration (FDA) by the manufacturer at the beginning of 2010. However, the FDA’s review cycle, which was announced late in 2010, concluded that the application could not be approved in its present form. The FDA’s complete response letter included comments related to clinical trials, statistical analysis and chemistry, manufacturing and controls. The FDA requested that the company should conduct two new phase III clinical trials using the commercial formulation, one in patients with T1D and the other in patients with T2D, to establish efficacy and safety with regard to hypoglycaemia and toleration. Co-administration of hyaluronidase together with insulin is another novel concept which has been proven to accelerate the absorption of both insulin lispro and regular human insulin in healthy subjects. In this review, we comment on two recent publications in which the pharmacokinetic and pharmacodynamic characteristics of Linjeta and co-formulations of prandial insulins with recombinant human hyaluronidase were investigated in patients with T1D. Lastly, a recent review on the ongoing discussion regarding insulin treatment and cancer risk is included.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1766d770d72b1a142635e01ad7a17871Test
https://doi.org/10.1089/dia.2015.1505Test