Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
Insulins may be grouped as short-acting, rapid-acting, intermediate-acting, long-acting insulin analogues or mixtures of these. Short-acting (soluble) insulins are absorbed more slowly than expected as the insulin molecules form relatively stable hexamers.Rapid-acting insulin analogues have a faster onset of action because their altered amino acid sequences reduce hexamer formation.Intermediate-acting insulins have a slower absorption into the bloodstream due to the addition of a protein and/or zinc; the protein protamine is commonly used.Long-acting (basal) insulin analogues have a prolonged duration of action due to factors that further slow the absorption from the injection site.
Drug Targeting to the Lung: Chemical and Biochemical Considerations
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Millions of lives of patients with diabetes have been saved since the introduction of insulin therapy. However, several daily injections of insulin are required to maximize glucose control in diabetic patients. Insulin is administered by subcutaneous injection, but this route of administration has a slow onset and subsequent prolonged duration of action. These limitations show up more when higher doses of insulin are injected, which results in a long duration of action and forces the patients to consume additional amounts of food to limit the risk of hypoglycemia (Anderson et al. 1997). This limitation has been reduced by the availability of newer, short-acting insulin analogues (Lispro, Aspart, and Glulisine). However, these forms of insulin must be injected subcutaneously (Bode et al. 2011). Technosphere™ insulin is a formulation of regular human and a new drug-delivery system for pulmonary administration. The formulation is designed for efficient transport of insulin across the intact respiratory epithelium into the systemic circulation (Owens 2002); its duration of action is more than 3 hours, and maximal serum insulin levels can be reached within 13 minutes after inhalation (Steiner et al. 2002), which is considerably shorter than those observed with rapid-acting insulin analogues administered subcutaneously or other insulin inhalations (Skyler et al. 2001).
Diabetes in pregnancy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in 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.
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
To improve basal insulin replacement therapy in type 1 diabetes beyond the current long-acting insulin analogues, several approaches may be relevant. Firstly, basal insulin can be administered as rapid-acting insulin in an insulin pump. This provides the opportunity to apply hybrid closed-loop technology, which can administer basal insulin based on CGM feedback, a step toward the artificial pancreas [76,77]. Alternatively, ultra-long-acting insulin analogues as the novel once-weekly insulin icodec may provide even flatter and more predictable action profiles, which may benefit at least some patients [74]. A more liver-specific insulin would potentially further restore metabolism by reducing peripheral hyperinsulinemia, which may also reduce the risk of hypoglycemia. In fact, insulin LY2605541, a pegylated insulin lispro showed increased liver specificity [78] and superior glucose lowering efficiency compared to glargine U100 together with a reduced risk of hypoglycemia [79]. The development program has, however, been stopped due to concerns about unwanted effects on the liver and lipid metabolism. The ultimate solution for a long-acting insulin is a glucose-sensitive insulin, which may provide efficient glucose control without promoting hypoglycemia [80].
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
Since the discovery of insulin, great efforts have been made to develop effective needle-free insulin delivery technology worldwide. The insulin pens inject insulin into the subcutaneous tissue through needles, which involve skin penetration. Insulin administration using jet injectors, which provide a needle-free alternative to insulin pens, are already available for clinical application. The jet injector pushes insulin in a drug tube at high velocity (typically > 100 m/s) across the skin, dispensing it over a larger subcutaneous area than insulin injected with a needle [12]. Due to the lack of needles, this technique provides little stimulation of subcutaneous nervous tissue, produces a weak stinging sensation, and the drug solution can be absorbed diffusely under the skin, close to the mode of human insulin secretion. The body absorbs the insulin more quickly, and the insulin works faster. Patients with T2DM treated with rapid-acting insulin using jet injection had a significantly shorter onset time of insulin and significantly improved early postprandial glucose control compared with those when using insulin pens [13,14]. Compared with traditional needle injection, this jet injection has irreplaceable technical advantages.
Practical guidance on the initiation, titration, and switching of basal insulins: a narrative review for primary care
Published in Annals of Medicine, 2021
Roopa Mehta, Ronald Goldenberg, Daniel Katselnik, Louis Kuritzky
Advice regarding missed or double doses depends on the pharmacologic characteristics of each basal insulin product (Table 1) [20,25–29]. In general, if the patient thinks they have missed a dose, they should test their FPG and contact their care team. Again, the flexibility and stable glucose-lowering action of long-acting insulin analogs help in this regard. For insulin degludec, for example, patients who realize they have missed a dose can inject it during waking hours the same day, as long as they ensure at least 8 h between consecutive injections [27]. If a double dose is taken, we suggest that patients should test their blood sugar frequently during the day, eat a snack and, in the night, wake up every 2–3 h to test glucose (with an extra snack if the reading is <126 mg/dL).
Related Knowledge Centers
- Diabetes
- Hyperglycemia
- Hyperosmolar Hyperglycemic State
- Type 1 Diabetes
- Type 2 Diabetes
- Insulin
- Gestational Diabetes
- Medication
- Pharmacy
- Diabetic Ketoacidosis