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Published in Henry J. Woodford, Essential Geriatrics, 2022
If targets are still not being met, commencing insulin is an option. Once-daily basal insulin (especially if administered by an external agency) or twice daily long-acting insulin formulations have a lower risk of hypoglycaemia. When starting insulin, it is usual to continue metformin, if no adverse effects, but consider stopping other oral antidiabetic drugs.91 A study (n = 14,616; mean age 60) has suggested that all-cause mortality may be higher when insulin, rather than a sulfonylurea, is added to metformin (HR 1.44, 95% CI 1.15–1.79).121
Immunosuppressants, rheumatic and gastrointestinal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
More recently, the native human insulin molecule has been genetically modified to alter the absorption kinetics of insulin in an attempt to achieve more physiological insulin concentrations, both basally and post prandially [2]. Insulin preparations are divided into 2 forms, based on their pharmacokinetic profiles: long-acting preparations that are used for basal insulin replacement, and faster-acting preparations that are used to control post-prandial rises in blood glucose. An ideal long-acting insulin preparation would produce relatively constant plasma concentrations of insulin over a 24-hour period, while an ideal short-acting preparation would have a rapid onset and peak of action, but a short overall duration, allowing quick and effective glucose disposal following a meal, whilst reducing the risk of hypoglycaemia due to residual absorption several hours following a meal; the combination mimicking normal physiological insulin secretion (Figure 1).
Insulins and insulin management
Published in Janet Titchener, Diabetes Management, 2020
Insulins are delivered either subcutaneously or inhaled. Tables 5.1, 5.2 categorise the available subcutaneous insulins according to which company produces them and whether they are traditional or analogue. Each insulin has a unique pharmacokinetic or action profile that includes either a basal component, a bolus component or, in the case of the traditional insulins, both basal and bolus components. The simplest way to approach insulin management is to determine which part of a person’s physiologic insulin profile (basal versus bolus) you wish to replace and then select an insulin with a pharmacokinetic profile that has the best match.
The role of Recent Pharmacotherapeutic Options on the Management of Treatment Resistant Type 2 Diabetes
Published in Expert Opinion on Pharmacotherapy, 2022
Jeffrey M. Kroopnick, Stephen N. Davis
For patients with type 2 diabetes who are initiating insulin, whether it be in addition to or replacement of oral agents or as initial pharmacotherapy, basal insulin is typically started prior to mealtime insulin [3]. Basal insulin can improve overnight and fasting blood sugars as compared to mealtime insulins, which will serve to treat postprandial hyperglycemia. Basal insulin may include intermediate-acting, neutral protamine Hagedorn (NPH) or longer-acting, detemir, glargine, or degludec. These may be administered once-daily or twice daily, in the case of NPH and detemir [3]. Hypoglycemia is a considerable concern and glargine, detemir, and degludec may have less nocturnal hypoglycemia as compared to NPH. In a meta-analysis of roughly 2200 subjects comparing glargine to NPH in patients with type 2 diabetes mellitus, there was a significant reduction of hypoglycemia risk with glargine compared to NPH, both symptomatically (11% reduction, p = 0.0006) and nocturnal hypoglycemia (26% reduction, p < 0.0001) [35]. Further, in a meta-analysis of four studies evaluating the efficacy and hypoglycemia of glargine and NPH in conjunction with oral anti-hyperglycemic agents, metformin plus a sulfonylurea or a sulfonylurea alone, in patients with type 2 diabetes mellitus, overall hypoglycemia (RR 0.95, p = 0.041), and nocturnal hypoglycemia (RR 0.73, p < 0.001) were significantly lower with glargine compared to NPH [36].
Novel approaches to pharmacological management of type 2 diabetes in Japan
Published in Expert Opinion on Pharmacotherapy, 2021
If a basal insulin analogue is injected subcutaneously, it does not enter the portal flow, as mentioned above, yet it stabilizes the fasting blood glucose level. When the fasting blood glucose level decreases to about 110 mg/dL (physiological level) and if β-cell function remains sufficient, endogenous blood glucose level-dependent insulin secretion can recover [88]. The secreted endogenous insulin enters the liver cells via the portal vein together with the glucose of food origin, absorbed into the superior mesenteric vein, thereby lowering the postprandial blood glucose level in a physiological manner [88–90]. It is desirable that the exogenously replenished basal insulin manifests continuous activity in a manner similar to physiologically secreted basal insulin. From this point of view, long-acting insulin preparations requiring only one dose per week seem promising as a means of treatment.
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].