Dataset Information

Concentrated insulins: the new basal insulins.

ABSTRACT: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed.This review highlights the published reports of the pharmacokinetic (PK) and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market.Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration.

SUBMITTER: Lamos EM

PROVIDER: S-EPMC4790523 | biostudies-other | 2016

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Concentrated insulins: the new basal insulins.

Lamos Elizabeth M EM Younk Lisa M LM Davis Stephen N SN

Therapeutics and clinical risk management 20160309

<h4>Introduction</h4>Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed.<h4>Areas covered</h4>This review highlights the published reports of the pharmacokinetic (PK) and glucodynamic prope ...[more]

PMID: 27022271

Similar Datasets

Project description:IntroductionAccording to Chinese guidelines, basal insulin (BI) or premixed insulins are recommended insulin starters following the failure of oral antihyperglycemic medication (OAM) in Chinese patients with type 2 diabetes (T2D). This pragmatic study investigated the long-term effectiveness, safety, and cost of add-on BI and mid-mixture insulin analog (MMI) regimens in Chinese patients with T2D.MethodsThis multicenter, open-label, pragmatic study randomized patients 1:1 to receive either BI or MMI with OAMs adjusted according to current standards of care. We evaluated the change in glycated hemoglobin (HbA1c) from baseline, safety parameters, and antidiabetic medication costs.ResultsChange in HbA1c from baseline showed a statistically greater decrease at week 48 in the MMI group (MMI: - 2.03% [0.06] vs. BI: - 1.82% [0.06]; P < 0.05). Both groups showed decreases in fasting plasma glucose (mmol/L) (MMI: - 2.53 [0.14] vs. BI: - 3.19 [0.14]; P < 0.01) and postprandial glucose (mmol/L) (MMI: - 4.35 [0.22] vs. BI: - 4.33 [0.23]). More patients in the BI group showed increases in OAM use, while OAM use decreased in the MMI group. Both groups showed stable glycemic control with a very limited insulin dose change from week 24 to week 48. The incidence of total hypoglycemia was higher in the MMI group (MMI: 124% [30.7] vs. BI: 76% [18.5], P < 0.0001), but no incidence of severe hypoglycemia was reported in either group. Treatment costs, in terms of average daily cost and cost of glycemic control, were higher in the BI group.ConclusionIn long-term real-world use, the MMI and BI groups demonstrated improved glycemic control, with the MMI group showing more significant improvement than the BI group. Hypoglycemia incidence was higher in the MMI group, with no major safety issues through week 48. MMI is likely to provide better price value than BI for the treatment of T2D in Chinese patients.Trial registrationClinicalTrials.gov identifier: NCT03018938.

Project description:INTRODUCTION:The stable, ultra-long duration of action of insulin degludec (degludec) minimizes fluctuations in glucose-lowering activity over the daily (24-h) dosing period, and comparative studies with other basal insulins suggest that these properties translate into a lower risk of hypoglycemia at equivalent levels of glycemic control. Results from the real-world European multicenter, retrospective chart review study of 2550 patients with type 1 and type 2 diabetes (T1D and T2D) in routine clinical care EU-TREAT (NCT02662114) showed that patients benefited from improved glycemic control and significantly reduced rates of hypoglycemia following a switch to degludec. METHODS:In this post hoc analysis, EU-TREAT patients were stratified into good (≤ 7.5% HbA1c), intermediate (> 7.5 to ≤ 8.5% HbA1c), and poor (> 8.5% HbA1c) glycemic control at baseline to investigate the possibility of differential benefits, either improved control or reduced risk of hypoglycemia, whichever the need. Changes in HbA1c, overall hypoglycemia, and total insulin dose from baseline to 6 and 12 months follow-up were assessed for each group. RESULTS:For both T1D and T2D patients, those in good initial control experienced significant reductions in rates of hypoglycemia and total insulin dose following the switch, without compromising control. Those in poor initial control achieved significant improvements in HbA1c with no change in rates of hypoglycemia or total insulin dose. CONCLUSION:This analysis expands the findings of EU-TREAT by showing differential changes in the clinical endpoints depending on particular need. It introduces the possibility that the differential benefits of degludec could address two of the renowned clinical challenges faced when treating diabetes: improving glycemic control for optimal management of T1D and titrating insulin dose in T2D, both without fear of increased hypoglycemia. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02662114. FUNDING:Novo Nordisk A/S.

Project description:AimWe compared the effects of two types of basal insulin: long-acting insulin analogues vs. intermediate/long-acting human insulin, on diabetes-related complications in type 1 diabetes.MethodsA total of 1188 patients with type 1 diabetes who had recently started on long-acting insulin analogues or intermediate/long-acting human insulin were identified in 2004-2008 and followed until death or the end of 2013. Clinical outcomes included acute (i.e. hyperglycaemia, hypoglycaemia) and chronic (i.e. nephropathy, retinopathy, neuropathy, cardiovascular diseases) complications. Diabetes-related complications were measured as a composite outcome which included acute and chronic complications. Cox proportional hazards models were used to assess the time to event hazard ratio. Three propensity score (PS) methods were applied to adjust for baseline imbalances between basal insulin groups, including the PS-matching approach (as the main analysis), standardized mortality ratio weighting (SMRW) and inverse probability of treatment weighting (IPTW).ResultsLong-acting insulin analogues vs. intermediate/long-acting human insulin had a lower risk for a composite of diabetes-related complications {adjusted hazards ratios [aHRs] [95% confidence interval (CI)] 0.782 [0.639, 0.956], 0.743 [0.598, 0.924] and 0.699 [0.577, 0.846] according to the PS-matching approach, SMRW and IPTW, respectively}. Compared with intermediate/long-acting human insulin, using long-acting insulin analogues had a lower hypoglycaemia risk: aHRs (95% CI) 0.681 (0.498, 0.930), 0.662 (0.466, 0.943) and 0.639 (0.471, 0.867) from the PS-matching approach, SMRW and IPTW, respectively. No statistical differences were found between two types of insulin on individual chronic complications.ConclusionA trend of lower diabetes-related complications associated with long-acting insulin analogues vs. intermediate/long-acting human insulin was observed. A reduced hypoglycaemia risk with long-acting insulin analogues was confirmed in this 'real-world' study.

Dataset Information

Concentrated insulins: the new basal insulins.

Publications

Concentrated insulins: the new basal insulins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets