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Diabetes in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
A number of insulin analogs have come on the market. Insulin lispro and insulin aspart are short-acting insulins, with a more rapid onset of action than that of regular insulin. Each differs from natural human insulin by a single amino acid. They can be given immediately before a meal, which increases flexibility of lifestyle. Insulin lispro does not cross the placenta to any great extent (59), and insulin aspart appears to have similar properties (60,61). Insulin glargine and insulin detemir are long-acting insulins with at least 24 hours of duration of action. Their absorption curve appears to be flat with no peak, and so their use can mimic basal insulin production by the pancreas or that of a continuous subcutaneous insulin infusion pump. In isolated placental perfusion models, insulin glargine at therapeutic concentrations on the maternal side did not reach detectable levels in the fetus, and even at very high levels, the rate of transfer was low (62). No published studies regarding transplacental passage of insulin detemir were found. If long-acting insulin analogs are used in pregnancy, insulin glargine is preferred to insulin detemir at the present time.
Immunosuppressants, rheumatic and gastrointestinal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Insulin glargine has two additional positive charges in the form of 2 arginine molecules, which alter the isoelectric point of the insulin molecule leading to precipitation in the subcutaneous tissues, thus prolonging absorption [6]. Insulin glargine has onset of action at around 6 hours and has a broad peak of activity lasting approximately 24 hours. Substitution of insulin glargine for isophane insulin has been shown to reduce nocturnal hypoglycaemia in children and adolescents, when used in conjunction with a rapid-acting analogue [7,8].
Insulin Therapy for Diabetes: Current Scenario and Future Perspectives
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Yogesh A. Kulkarni, R. S. Gaud, Mayuresh S. Garud
Two novel and potentially improved formulations of insulin glargine as basal insulin supplementation are currently under development. One is LY2963016 by Eli Lilly and the second is BIOD-Adjustable Basal by Biodel. BIOD-Smart-Basal contains insulin glargine, glucose oxidase, and peroxidase. In the presence of glucose, glucose oxidase and peroxidase react to form gluconic acid, which lowers the pH and increases the solubility of insulin glargine and promotes its release into the circulation [34]. It can be premixed with other insulin products [34, 35]. Sanofi-Aventis is also developing a new basal insulin formulation. Insulin lispro protamine now is being tested as a stand-alone basal insulin analog in patients with type 1 and 2 diabetes [36, 37].
Efficacy and safety of Tregopil, a novel, ultra-rapid acting oral prandial insulin analog, as part of a basal-bolus regimen in type 2 diabetes: a randomized, active-controlled phase 2/3 study
Published in Expert Opinion on Pharmacotherapy, 2022
Harold E Lebovitz, Alexander Fleming, Alan D Cherrington, Shashank Joshi, Sandeep N Athalye, Subramanian Loganathan, Ashwini Vishweswaramurthy, Jayanti Panda, Ashwani Marwah
The major limitation of the study is its open-label design due to difference in routes of administration of the test and control drugs and the ethical challenges of the double-dummy design due to the daily administration of three SC injections of active control drug. The requirement of up-titration allowed up to a maximum of 8 weeks to achieve desired glycemic control was high, as ~90% of patients in the Tregopil 30 mg group were up-titrated to 45 mg for at least one of the doses daily. The dose of insulin glargine was fixed during the treatment period, unless for safety reasons. An increase in basal insulin dose may compensate for late phase PPH when the effect of Tregopil is reduced, thus contributing to FPG control. Additionally, the small size of the study population limited the statistical power and interpretation of results.
A case of asymmetric insulin-derived localised amyloid deposition associated with long-acting insulin analog administration
Published in Amyloid, 2022
Keiji Hirai, Shigeki Imamura, Aizan Hirai, Naoka Umemoto, Hisashi Oshiro, Fuyuki Kametani, Nagaaki Katoh, Masahide Yazaki, Susumu Ookawara, Yoshiyuki Morishita
The absorption rates of insulin after subcutaneous injection differ according to the analog used. Insulin glargine, a long-acting insulin analog, forms stable oligomers of hexameric insulin in subcutaneous tissue, from which insulin monomers are slowly released over 24 h [4]. In contrast, insulin aspart, a rapid-acting insulin analog, dissociates rapidly into monomers in subcutaneous tissue and is absorbed within 5 h [5]. In this case, the patient had injected insulin glargine on his left side for 15 years and insulin aspart on his right side for 14.5 years, which resulted in subcutaneous amyloid deposition only in his left abdominal wall. Therefore, the difference in the disappearance time of the insulin analogs from the subcutaneous tissue might explain the discrepancy in the formation of insulin-derived amyloid in his subcutaneous tissue. In the previous reports, the type of insulin involved was not identified because of the complex history of insulin use [1]. In contrast, specific type of insulin was identified as culprit for subcutaneous amyloid deposition in our case. Further accumulation of similar cases is needed to clarify the relationship between the type of insulin and the formation of insulin-derived amyloid.
Needle-free jet injection of insulin glargine improves glycemic control in patients with type 2 diabetes mellitus: a study based on the flash glucose monitoring system
Published in Expert Opinion on Drug Delivery, 2021
Xiaocen Kong, Menghui Luo, Ling Cai, Peng Zhang, Rengna Yan, Yun Hu, Huiqin Li, Jianhua Ma
Using the jet injector group led to significantly lower mean glucose levels from 12:00 to 22:00 compared to those when using the conventional insulin pen. Use of the jet injector and pen injections produced similar FBG levels. This underlying mechanism may be explained first by the administration of insulin glargine before breakfast (07:00). Insulin glargine is a long-acting insulin analog with well-established efficacy and safety profiles, with an onset time of 4 hours following subcutaneous injection [22,23]. The use of the needle-free jet injector treatment could increase the absorption rate of insulin glargine resulting in a faster onset of action. Second, patients included in this study had a small dose of insulin at 12–18 IU daily. There was no subcutaneous allergy or induration at the injection site on the abdominal skin. Therefore, the total absorption of insulin remained unchanged or changed slightly. Engwerda et al. reported that there were no differences in the variability of the efficacy endpoints between the jet injector and routine insulin pen administration [24]. Because the daily dose of insulin was constant, there was no difference in FBG between the two treatment methods.