Regular Human Insulin In Patients Research Articles

Insulin Aspart in the Management of Diabetes Mellitus: 15 Years of Clinical Experience.

Limiting excessive postprandial glucose excursions is an important component of good overall glycemic control in diabetes mellitus. Pharmacokinetic studies have shown that insulin aspart, which is structurally identical to regular human insulin except for the replacement of a single proline amino acid with an aspartic acid residue, has a more physiologic time–action profile (i.e., reaches a higher peak and reaches that peak sooner) than regular human insulin. As expected with this improved pharmacokinetic profile, insulin aspart demonstrates a greater glucose-lowering effect compared with regular human insulin. Numerous randomized controlled trials and a meta-analysis have also demonstrated improved postprandial control with insulin aspart compared with regular human insulin in patients with type 1 or type 2 diabetes, as well as efficacy and safety in children, pregnant patients, hospitalized patients, and patients using continuous subcutaneous insulin infusion. Studies have demonstrated that step-wise addition of insulin aspart is a viable intensification option for patients with type 2 diabetes failing on basal insulin. Insulin aspart has shown a good safety profile, with no evidence of increased receptor binding, mitogenicity, stimulation of anti-insulin antibodies, or hypoglycemia compared with regular human insulin. In one meta-analysis, there was evidence of a lower rate of nocturnal hypoglycemia compared with regular human insulin and, in a trial that specifically included patients with a history of recurrent hypoglycemia, a significantly lower rate of severe hypoglycemic episodes. The next generation of insulin aspart (faster-acting insulin aspart) is being developed with a view to further improving on these pharmacokinetic/pharmacodynamic properties.

Safety of intravenous insulin aspart compared to regular human insulin in patients undergoing ICU monitoring post cardiac surgery: an Indian experience.

BackgroundPoor perioperative glycemic control increases risk of infection, cardiovascular accidents and mortality in patients undergoing surgery. Tight glycemic control by insulin therapy is known to yield better outcomes in such patients. Intravenous (IV) insulin therapy with or without adjunctive subcutaneous insulin therapy is the mainstay of managing hyperglycemia in perioperative period. This observational study assessed the safety of IV Insulin Aspart (IAsp) as compared to Regular Human Insulin (RHI) in patients undergone cardiac surgery at a tertiary care hospital.Methods203 patients received IV IAsp (n = 103) and RHI (n = 100) respectively. Safety was assessed by frequency and severity of adverse events (AEs) & serious adverse events (SAEs) during hospitalization.ResultsIAsp effectively controlled mean blood glucose levels to 159.87 ± 41.41 mg/dl similar to RHI (160.77 ± 44.39 mg/dl). No serious adverse event was reported. The incidence of hypoglycemia was similar in both the groups. The insulin infusion rate, time for which insulin infusion was withheld and mean blood glucose during hypoglycemia was significantly high in RHI group.ConclusionThis study has shown similar safety of IV IAsp as compared to IV RHI in the post cardiac surgery patients. However physicians preferred IAsp as it offers advantage during transition. IV IAsp offers an effective and safe option for managing hyperglycemia in patients in ICU post cardiac procedures.

Clinical efficacy and safety of insulin aspart compared with regular human insulin in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

Prandial insulin is a key component in insulin treatment of type 1 diabetes mellitus (T1DM) and in many patients with type 2 diabetes mellitus (T2DM). The evidence-based data supporting the choice of an insulin preparation are still limited. We performed a systematic review to summarize and update the evidence on relative efficacy and safety of insulin aspart (IAsp) and regular human insulin (RHI) in both types of diabetes. Randomized controlled trials comparing IAsp with RHI in patients with either T1DM or T2DM and conducted until May 2013 were retrieved from a systematic search of MEDLINE, EMBASE, and Cochrane Library. Of 16 relevant trials, 11 involved patients with T1DM and 5--with T2DM. In the T1DM population, IAsp, when compared with RHI, provided a greater reduction in hemoglobin A₁c (HbA₁c) levels (weighted mean difference [WMD], -0.11%; 95% confidence interval [CI], -0.16 to -0.05; WMD, -1.2 mmol/mol; 95% CI, -1.7 to -0.5), and improved postprandial glucose levels following breakfast (WMD, -1.40 mmol/l; 95% CI, -1.72 to -1.07), lunch (WMD, -1.01 mmol/l; 95% CI, -1.61 to -0.41), and dinner (WMD, -0.89 mmol/l; 95% CI, -1.19 to -0.59). The risk of nocturnal hypoglycemia was lower in T1DM patients receiving IAsp (relative risk, 0.76; 95% CI, 0.64-0.91), while no difference was observed for severe hypoglycemia. In T2DM patients, IAsp led to a greater reduction in HbA₁c levels (WMD, -0.22%; 95% CI, -0.39 to -0.05; -2.4 mmol/mol, -4.3 to -0.5) and postprandial blood glucose. The risk of overall hypoglycemia and severe adverse effects was comparable between the groups. IAsp provides better glycemic control when compared with RHI in patients with T1DM and T2DM. Fewer T1DM patients treated with IAsp experienced nocturnal hypoglycemia, while both interventions showed a comparable risk of severe hypoglycemic events in both types of diabetes.

PDB4 - Clinical efficacy and safety of insulin aspart compared with regular human insulin in patients with type 1 and type 2 diabetes mellitus receiving prandial insulin regimen - a systematic review and meta-analysis

• Wrong methodology (73) • Wrong intervention (127) • Healthy subjects (2) • Wrong control group (14) • Non-comparable treatment schemes (18) • Secondary studies (53) • Inapropriate follow-up (92) • Less than10 pts (2) • Inappropriate language (8) • Letters, editorials, irrelevant subject (26) • Patients with ketoacidosis or gestational diabetes (10) • Endpoints of interest not reported (28) 469 articles assessed for eligibility ▼

Pharmacotherapy in Type 1 Diabetes

Pharmacotherapy in Type 1 Diabetes

Insulina aspart en pacientes con diabetes tipo 2

Current insulin therapy aims to mimic both basal and prandial physiological hormone secretion to achieve near-normal glycemia. Regular human insulin has been used for years for glycemic control in type 2 diabetes mellitus (DM-2). However, its pharmacokinetic and pharmacodynamic profiles have never been considered optimal. Due to its more physiological profile, insulin aspart has gradually been substituting regular human insulin in patients with DM-2 but there is ongoing debate concerning its efficacy and safety in these patients. Although insulin aspart has not been shown to produce significant decreases in HbA1c, some – but not all – studies have reported that this drug has beneficial effects in reducing postprandial hyperglycemia. Furthermore, at least in specific populations, insulin aspart may reduce the incidence of nocturnal hypoglycemic episodes and severe hypoglycemic episodes, a finding of importance in high-risk patients.

A Review of the Structure, Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Insulin Glulisine in the Management of Diabetes Mellitus

Glulisine (ApidraTM) is a rapid acting recombinant insulin analogue which differs from regular human insulin (RHI) by the substitution of lysine for asparagine at position B3 and glutamic acid for lysine at position B29. The chemical name is 3B-Lys-29- B-Glu-human insulin. The amino acid substitutions of glulisine and other rapid acting insulin analogues promote monomer stability, allowing for rapid dissociation and absorption after subcutaneous injection. It has a favourable pharmacokinetic and pharmacodynamic profile when compared with RHI, characterised by quicker absorption and a greater early disposal of glucose, thus replicating a more physiological response to a meal. It has been demonstrated to be superior to RHI in patients with Type 1 diabetes mellitus (DM) and at least non-inferior in the management of Type 2 DM with respect to reducing HbA1c and post-prandial glucose excursions, with a comparable safety profile. In efficacy trials comparing glulisine with lispro in patients with type 1 DM, glulisine was non-inferior with no significant difference in change in HbA1c or post-prandial glucose levels. However, although glulisine and lispro have been demonstrated to induce comparable total glucose disposals in normal subjects, glulisine causes earlier glucose disposal in both lean and obese subjects, has significantly faster subcutaneous absorption along with similar rates of adverse events, hypoglycemia and weight gain. There are limited data comparing the pharmacokinetics, pharmacodynamics, efficacy and safety of glulisine and aspart insulins.

Postprandial Vascular Effects of VIAject Compared With Insulin Lispro and Regular Human Insulin in Patients With Type 2 Diabetes

OBJECTIVERecent studies suggested an impact of prandial insulin delivery on postprandial regulation of tissue blood flow. This study compared the effect of VIAject with human regular insulin and insulin lispro on postprandial oxidative stress and endothelial function in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSFourteen patients (seven men; aged 61.5 ± 1.8 years; duration of diabetes 6.6 ± 4.6 years; A1C 7.2 ± 0.5% [mean ± SEM]) received a prandial injection of VIAject, human regular insulin, and insulin lispro. At baseline and after a standardized liquid meal test (Ensure Plus), the postprandial increases in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the postprandial effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured.RESULTSTreatment with VIAject resulted in a significant reduction in the peak postprandial generation of ADMA compared with human insulin and insulin lispro (VIAject −27.3 ± 22.6, human insulin 97.7 ± 24.4, and insulin lispro 66.9 ± 33.9 nmol/l; P < 0.05, respectively). The postprandial increases in nitrotyrosine levels were significantly less after VIAject than after human regular insulin (VIAject −0.22 ± 0.17 vs. human insulin 0.25 ± 0.15 μg/ml; P < 0.05), whereas nitrotyrosine after insulin lispro was in between (insulin lispro 0.09 ± 0.07 μg/ml; NS). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after VIAject compared with those after human insulin or insulin lispro (P < 0.05, respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity.CONCLUSIONSTreatment with VIAject reduced postprandial oxidative stress and improved endothelial function compared with human regular insulin or insulin lispro.

Defining the Role of Insulin Lispro in??the Management of Postprandial Hyperglycaemia in Patients with Type??2 Diabetes Mellitus

The role of postprandial hyperglycaemia in contributing to the risk of both micro- and macrovascular complications in patients with diabetes mellitus is being increasingly recognized. In type 2 diabetes, there is a progressive shift in the relative contributions of postprandial and fasting hyperglycaemia to the overall glycaemic control as the disease progresses. For patients with fairly good glycaemic control (glycosylated haemoglobin [HbA(1c)] <8.5%), postprandial hyperglycaemia makes a relatively greater contribution to the overall glycaemic load than fasting hyperglycaemia, but in patients with poorer control, the relative contribution of the two states to the overall glycaemic load is reversed. This finding, coupled with epidemiological evidence that elevated postprandial glucose concentration is an independent risk factor for cardiovascular disease (CVD), and is associated with a greater CVD risk than elevated fasting glucose, points to the need to monitor and target postprandial glucose, as well as fasting glucose and HbA(1c) levels, when optimizing insulin therapy for patients with type 2 diabetes. When insulin therapy becomes necessary in patients with type 2 diabetes who can no longer be controlled with oral antihyperglycaemic therapy, use of short-acting insulin analogues with a rapid onset of action and capable of controlling postprandial glycaemic excursions when injected immediately before a meal, has advantages over regular human insulin in that they provide a more favourable time-action profile that mimics normal physiological insulin secretion. Among the available rapid-acting insulin analogues, insulin lispro has been shown to reduce postprandial glucose concentrations to a significantly greater degree than regular human insulin in patients with type 2 diabetes. Moreover, premixed combinations of insulin lispro with the longer acting analogue neutral insulin lispro protamine suspension in 25% : 75% or 50% : 50% combinations are significantly more effective in lowering postprandial blood glucose concentrations than premixed regular human insulin plus neutral protamine Hagedorn (NPH) 30% : 70%. The premixed insulin lispro combinations offer the advantage of fewer daily injections than intensive insulin therapy, and the convenience of not having to mix insulin preparations manually. Although it has yet to be conclusively established that targeting postprandial hyperglycaemia reduces CVD risk, the potential benefits of improved postprandial and interprandial hyperglycaemia favour the use of newer insulin analogues, such as insulin lispro and insulin lispro mixes, over conventional insulin therapy, whenever insulin therapy becomes necessary in patients with type 2 diabetes.

Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus

Short acting insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. To assess the effects of short acting insulin analogues versus regular human insulin. The Cochrane Library (Issue 3, 2005), MEDLINE, EMBASE until September 2005. Randomised controlled trials with an intervention duration of at least 4 weeks. Trial selection and evaluation of study quality was done independently by two reviewers. Altogether 8274 participants took part in 49 randomised controlled studies. Most studies were of poor methodological quality. In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was -0.1% (95% CI: -0.2 to -0.1) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was 0.0% (95% CI: -0.1 to 0.0). In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3 to -0.1) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII), whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.1 to 0.0). The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.1 to 0.7) and -0.2 (95% CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively. For studies in type 1 diabetes patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 21.8) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 46.1) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.3) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 1.4) for regular insulin. No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications. Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.

Exubera inhaled insulin: a review.

The focus of this review is inhaled insulin, specifically Exubera, which represents a novel prandial insulin delivery method. Fear of hypoglycaemia and the reluctance of patients to use multiple daily injection regimens is a major barrier to achieving good glycaemic control in patients with type 1 and type 2 diabetes. Inhaled insulin has been developed to provide more physiological prandial insulin replacement than regular human insulin in patients with diabetes, with the advantage of non-invasive delivery. Good glycaemic control, comparable to modern subcutaneously administered insulin preparations, has already been demonstrated, and no unexpected safety concerns have been reported with inhaled insulin. The development of such insulin delivery technologies that are better tailored to patients' needs may improve patient compliance, thereby facilitating the attainment of treatment targets. This review summarises the studies available and discusses the potential implications to patients of needle-free insulin administration.

Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus.

In short acting insulin analogues the dissociation of hexamers is facilitated, achieving peak plasma concentrations about twice as high and within approximately half the time compared to regular human insulin. According to these properties this profile resembles the shape of non-diabetic patients more than that of regular human insulins. Despite this theoretical superiority of short acting insulin analogues over regular human insulin, the risk-benefit ratio of short acting insulin analogues in the treatment of diabetic patients is still unclear. To assess the effect of treatment with short acting insulin analogues versus regular human insulin. A highly sensitive search for randomised controlled trials combined with key terms for identifying studies on short acting insulin analogues versus regular human insulin was performed using the Cochrane Library (issue 1, 2003), MEDLINE and EMBASE. Date of last search was December 2003. We included randomised controlled trials with diabetic patients of all ages that compared short acting insulin analogues to regular human insulin. Intervention duration had to be at least 4 weeks. Trial selection as well as evaluation of study quality was done by two independent reviewers. The quality of reporting of each trial was assessed according to a modification of the quality criteria as specified by Schulz and Jadad. Altogether 7933 participants took part in 42 randomised controlled studies. Most studies were of poor methodological quality. In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was estimated to be -0.1% (95% CI: -0.2% to -0.1%) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was estimated to be 0.0% (95% CI: -0.1% to 0.1%). In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3% to -0.1%) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII) whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.2% to -0.0%). The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.2 to 0.9) and -0.2 (95%CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively. For studies in type 1 diabetic patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 20.3) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 37.2) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.6) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 2.8) for regular insulin. No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications. Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. Due to fears of potentially carcinogenic and proliferative effects, most studies to date have excluded patients with advanced diabetic complications. For safety purposes, we need a long-term follow-up of large numbers of patients who use short acting insulin analogues. Furthermore, we need well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.

Insulin aspart: a review of its use in the management of type 1 or 2 diabetes mellitus.

Insulin aspart (NovoRapid, NovoLog) is a short-acting insulin analogue, which has a faster onset and shorter duration of action than regular human insulin. Insulin aspart administered immediately before meals provided significantly greater improvements in glycosylated haemoglobin and better postprandial glycaemic control than regular human insulin administered 30 minutes before meals, when used in a basal-bolus regimen with neutral protamine Hagedorn (NPH) insulin, in randomised, nonblind studies in patients with type 1 diabetes mellitus. In patients with type 2 diabetes, insulin aspart provided similar glycaemic control to regular human insulin, administered in a basal-bolus regimen with NPH insulin. Small studies suggest that the use of insulin aspart in combination with oral hypoglycaemic agents may be beneficial. Insulin aspart, administered by continuous subcutaneous insulin infusion (CSII) provided better glycaemic control than insulin aspart multiple daily injection regimens in patients with type 1 (but not type 2) diabetes, and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Limited studies show insulin aspart to be effective in children, adolescents and young adults with type 1 diabetes. Insulin aspart had a tolerability profile similar to that of regular human insulin in clinical trials. The incidence of major or nocturnal hypoglycaemic events reported in patients receiving insulin aspart was lower than that of regular human insulin in several studies. In conclusion, insulin aspart, administered immediately before meals in a basal-bolus regimen with NPH insulin, provided better long-term glycaemic control than regular human insulin administered 30 minutes before meals in patients with type 1 diabetes, and was as effective as regular human insulin in patients with type 2 diabetes. A significantly lower risk of hypoglycaemia was seen in several trials. Insulin aspart CSII provided better glycaemic control than insulin aspart multiple daily subcutaneous injection (MDI) in patients with type 1 (but not type 2) diabetes and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Insulin aspart is an effective and well tolerated alternative to regular human insulin and insulin lispro for the maintenance of glycaemic control in patients with type 1 or 2 diabetes.

Spotlight on Insulin Aspart in Type 1 and 2 Diabetes Mellitus*

Insulin aspart (NovoLog, NovoRapid), a rapid-acting human insulin analog, provides more rapid absorption than regular human insulin after subcutaneous administration. In most randomized, nonblind clinical trials in patients with type 1 diabetes mellitus, insulin aspart administered immediately before meals resulted in significantly lower mean glycosylated hemoglobin (HbA1c) levels than regular human insulin (usually administered 30 minutes before a meal). Insulin aspart also significantly improved postprandial glycemic control compared with regular human insulin. The efficacy of insulin aspart was similar to that of insulin lispro when administered to patients with type 1 diabetes mellitus via continuous subcutaneous infusion in a randomized, nonblind trial. Preliminary data from randomized, nonblind trials suggest insulin aspart had a trend towards lower HbA1c levels compared with regular human insulin in patients with type 2,diabetes mellitus. Biphasic insulin aspart (30% soluble [rapid-acting] and 70% protamine-bound insulin aspart [BIAsp30]) [NovoLog Mix 70/30, NovoMix 30(2)] generally provided significantly better postprandial glucose control than a similar mixture of biphasic regular human insulin (BHI30) in a randomized, nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a randomized, nonblind trial in patients with type 2 diabetes mellitus. Patients with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with insulin aspart or BIAsp30 than with regular human insulin or BHI30. The overall incidence of hypoglycemia with insulin aspart was lower than, or similar to, that of regular human insulin. Moreover, insulin aspart tended to be associated with a lower occurrence of nocturnal hypoglycemia and severe hypoglycemic events than regular human insulin. The standard preparation of insulin aspart has the potential to better mimic the physiological response to meals than regular human insulin. Insulin aspart when combined with a suitable basal insulin improved overall glycemic control and led to a similar or lower number of hypoglycemic episodes compared with a similar regular human insulin regimen. Insulin aspart was generally as effective and well tolerated as insulin lispro when administered by continuous subcutaneous infusion in a single comparative trial. The efficacy of biphasic insulin aspart has been documented in a small number of trials. Both insulin aspart and biphasic insulin aspart provide for flexible and convenient administration. Insulin aspart is now well established as an effective and convenient means of providing glycemic control which offers clinical and practical advantages over regular human insulin.

A comparison of insulin lispro and buffered regular human insulin administered via continuous subcutaneous insulin infusion pump

This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) using an external insulin pump. In this 24-week multicenter, randomized, two-way crossover, open-label trial, 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks, followed by the alternate treatment for another 12 weeks. Efficacy and safety measures included hemoglobin A 1c (HbA 1c) at baseline and endpoint, home blood glucose monitoring, hypoglycemia, and frequency of pump catheter occlusion. Patients consumed a standard test meal on three occasions, with determinations of fasting, 1- and 2-h postprandial glucose values. Insulin lispro use was associated with a significantly lower HbA 1c than was buffered regular human insulin (7.41±0.97 vs. 7.65±0.85 mmol/l; P=.004). Fasting serum glucose values before the test meal were similar between the two therapies. The 1-h (11.16±4.29 vs. 13.20±4.68 mmol/l; P=.012) and 2-h (9.64±4.10 vs. 12.53±4.64 mmol/l; P=.001) postprandial glucose concentrations were significantly lower during treatment with insulin lispro. No differences between treatments were observed in basal or bolus insulin doses, weight gain, or the incidence and rate of hypoglycemia, hyperglycemia, or pump occlusions. When used in external pumps, insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile.

Intravenous administration of insulin lispro versus regular human insulin in patients with type 1 diabetes

Intravenous administration of insulin lispro versus regular human insulin in patients with type 1 diabetes