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Pregestational Diabetes
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
F. Weston Loehr, A. Dhanya Mackeen, Michael J. Paglia
Though satisfactory glucose control may be obtained solely with an intermediate-acting insulin rather than a short-acting insulin [57], we suggest optimizing metabolic control with one evening injection of long-acting insulin (e.g., insulin glargine), and meal-time (three daily) injections of short-acting insulin (e.g., lispro or aspart) (Figures 5.1 and 5.2). Glargine cannot be mixed in the same syringe with other insulins. Intermediate-acting insulin (e.g., neutral protamine Hagedorn [NPH]) twice daily can also be used, instead of insulin glargine. Studies have shown that short-acting insulin is as effective as regular insulin and may result in improved postprandial glucose control and less preterm deliveries [58, 59]. Insulin lispro should be given immediately before eating. As compared to two daily insulin injections, additional doses are associated with improved glycemic control [60]. A meta-analysis of cohort studies comparing insulin glargine to NPH did not reveal any significant differences in outcomes including infant birth weight, congenital anomalies, and respiratory distress [61]. A large randomized trial including 310 pregnancies compared insulin detemir with NPH and found no differences between maternal HgbA1c, the frequency of major hypoglycemic episodes [62], early fetal loss, congenital anomalies, or adverse events [63]. Insulin analogs have not been associated with an increased risk of congenital anomalies [64].
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.
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
Last two decades have seen a remarkable change and gradual refinement in the molecular structure of insulin. Different rapid-acting and long-acting insulin analogs were prepared that can closely imitate endogenous insulin. A number of them were successfully marketed and are being used to get good glycaemic control. But there are also stories of failure. Recently, Eli Lilly have finished the development of a novel basal insulin analog, LY2605541, which was on its way to phase III trials. The reason could be related to liver toxicity [40].
Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial
Published in Current Medical Research and Opinion, 2022
Jun Yao, Xiaohui Guo, Li Sun, Ping Han, Xiaofeng Lv, Xiuzhen Zhang, Zhaohui Mo, Wenying Yang, Lihui Zhang, Zhanjian Wang, Lvyun Zhu, Quanmin Li, Tao Yang, Wenbo Wang, Yaoming Xue, Yongquan Shi, Juming Lu, Yongde Peng, Fan Zhang, Dewen Yan, Damei Wang, Xuefeng Yu
Over the last few decades, specialized insulin analogs have been developed by altering the amino acid structure of recombinant human insulin to provide additional benefits in terms of stability and speed of action3. Insulin aspart, a rapid-acting insulin analog, has an amino acid substitution at position B28 (proline substituted with aspartic acid)6. This substitution decreases insulin hexamer formation and promotes depolymerization, resulting in peak glucose infusion rates that are higher and occur earlier compared with human insulin, allowing administration immediately before a meal7,8. Typical onset of action for insulin aspart is 10–30 min following administration, with peak efficacy at 1–2 h and duration of effect of 3–6 h8,9. Most commonly, fast-acting analogs are administered using insulin pens, but can also be given via syringe and insulin pumps3. Treatment with rapid-acting insulin analogs, including insulin aspart, leads to improved blood glucose management without increasing the rate of hypoglycemia. However, the expense of currently available insulin analogs can be prohibitive for many patients, particularly in middle and lower-income countries3,10.
Synthetic long-acting insulin analogs for the management of type 1 diabetes: an update
Published in Expert Opinion on Pharmacotherapy, 2021
Ulrik Pedersen-Bjergaard, Therese W. Fabricius, Birger Thorsteinsson
A range of long-acting insulin analogs have been developed. While the first-generation analogs insulin detemir and insulin glargine U100 still in many cases need to be administered twice daily to provide full basal insulin coverage, they provide non-inferior glucose-lowering and reduce the risk of nocturnal and severe hypoglycemia as compared to human NPH insulin. The newer analogs insulin glargine U300 and insulin degludec both provide full basal insulin coverage by once-daily therapy and they both provide non-inferior efficacy, although insulin glargine U300 is less potent unit-to-unit, as compared to insulin glargine U100 and insulin degludec. Insulin degludec provides further reduction of hypoglycemia risk as compared to insulin glargine U100, particularly nocturnal hypoglycemia. Future studies should explore the potential for further improvement of treatment results in type 1 diabetes by structured approach to personalization of basal insulin therapy.
Pharmacologic treatment options for type 1 diabetes: what’s new?
Published in Expert Review of Clinical Pharmacology, 2019
Laura M. Nally, Jennifer L. Sherr, Michelle A. Van Name, Anisha D. Patel, William V. Tamborlane
As laboratory methods advanced, scientists were able to modify the chemical structure of insulin to allow it to be absorbed more rapidly [1]. In contrast to regular human insulin, with a duration of action up to 7–8 hours, the more rapid absorption of lispro, aspart and glulisine insulins were better able to mitigate early post-meal peaks in plasma glucose and decrease the risk of late post-prandial hypoglycemia [2]. Moreover, the lower peaks and longer-duration of action of new long-acting basal insulin analogs like glargine and detemir provided a better means to regulate overnight and between meal glucose control. Additionally, exclusive use of rapid-acting insulin analogs in insulin pump therapy allowed clinicians and patients to tailor insulin doses more precisely. In head-to-head comparisons, CSII was able to surpass multiple daily injections (MDI) treatment for T1D over glargine and isophane insulin types [3–5].