			Home About us Contact

Insulin Analogues (insulin + analogue)

Distribution by Scientific Domains

Medical Sciences	97%

Distribution within Medical Sciences

Diabetes	90%
Pharmacology & Pharmaceutical Medicine	4%

Kinds of Insulin Analogues

basal insulin analogue

long-acting insulin analogue

rapid-acting insulin analogue

Selected Abstracts

Insulin analogues: an example of applied medical science

DIABETES OBESITY & METABOLISM, Issue 1 2009
B. Sheldon
Insulin analogues were developed to try and achieve more physiological insulin replacement from injection in the subcutaneous site. Their pharmacokinetics and pharmacodynamics differ from human insulin when injected subcutaneously because of alterations in the amino acid sequence of the insulin molecule. The rapid-acting insulin analogues, lispro, aspart and glulisine, have a rapid onset of action and shorter duration of action because of changes to the B26,30 portion of insulin inhibiting formation of dimers and hexamers. They appear to improve postprandial glucose, incidence of hypoglycaemia and patient satisfaction and, when used in combination with basal insulin analogues, improve glycosylated haemoglobin in comparison to conventional insulin therapy. Additionally, they have been successfully used in children, pregnant women, in pump therapy and as part of premixed biphasic regimens. The two basal insulin analogues, glargine and detemir, developed by adjusting the isoelectric point and adding a fatty acid residue, respectively, have a protracted duration of action and a relatively smooth profile. Their pharmacokinetic and pharmacodynamic profiles have been assessed using euglycaemic clamp protocols. Both analogues have a longer duration of action, less of a peak of activity and a reduced variability with repeated injection. There is some evidence to suggest that detemir may have a slight hepatoselective effect. Clinical studies have shown a lower relative risk of hypoglycaemia and detemir appears to have a weight-sparing action. Insulin analogues represent a successful example of applied medical science. [source]

Novel insulin analogues and its mitogenic potential

DIABETES OBESITY & METABOLISM, Issue 6 2006
Ivana Zib
Abstract:, Insulin analogues were developed to modify the structure of the human insulin molecule in order to more accurately approximate the endogenous secretion of insulin. With the help of recombinant technology and site-directed mutagenesis, the insulin molecule can be modified to either delay or shorten absorption time, providing better insulin treatment options and facilitating the achievement of glycaemic goals. Changing the structure of the insulin molecule, however, may significantly alter both its metabolic and mitogenic activity. Multiple factors such as residence time on the receptor, dissociation rate, rate of receptor internalization and the degree of phosphorylation of signalling proteins can affect the mitogenic potencies of insulin analogues. Changes in the structure of the insulin have raised concern about the safety of the insulin analogues. For example, questions have emerged about the relationship between the use of insulin lispro and insulin glargine and the progression of diabetic retinopathy. Two studies have shown progression of retinopathy with the use of insulin lispro. However, others have not confirmed these results, and causality could not be proven as progression of retinopathy can occur with rapid improvement in glycaemic control, and methods of assessments among studies were not consistent. Therefore, we examine the metabolic and mitogenic characteristics of the three insulin analogues, insulin lispro, insulin aspart and insulin glargine, that are currently on the market, as well as the two insulin analogues, insulin glulisine and insulin detemir, that are soon going to be available for clinical use. [source]

Appraising the mitogenicity of insulin analogues relative to human insulin,response to: Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activity in cultured cancer cells.

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2010
Diabetes Metab Res Rev 2009; 25(1): 4
Abstract Interest in mitogenic and potentially carcinogenic effects of insulin and insulin analogues has been renewed by several recent publications that have examined the relationship between cancer and insulin analogues. Actions mediated through the insulin-like growth factor-I receptor in a hyperinsulinaemic state have been implicated mechanistically. Both type 2 diabetes and endogenously elevated insulin-like growth factor-I have been epidemiologically linked to malignancies. Therefore, in vitro mitogenic effects and binding affinities of the various analogues have been analysed. A recent publication by Weinstein et al. studied the in vitro mitogenic and anti-apoptotic activities of insulin analogues, and their conclusion asserts that insulins glargine, detemir, and lispro displayed proliferative and anti-apoptotic effects in a number of malignant cell lines. However, their conclusions are not supported by the data which are not complete and lack clear statistical significance. This data should be interpreted cautiously in light of all other presently available scientific evidence. Prospective, randomized clinical trials will best address any direct relationship between insulin analogues and cancer. Until those studies are designed and completed, clinicians should consider the demonstrated strong benefit of glycaemic control in balance with any alleged risk. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Continuous subcutaneous insulin infusion (CSII) 30 years later: still the best option for insulin therapy

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2009
Daniela Bruttomesso
Abstract Thirty years after its introduction, the use of continuous subcutaneous insulin infusion (CSII) keeps increasing, especially among children and adolescents. The technique, when used properly, is safe and effective. Compared with traditional NPH-based multiple daily injections (MDI), CSII provides a small but clinically important reduction of HbA1c levels, diminishes blood glucose variability, decreases severe hypoglycaemic episodes and offers a better way to cope with the dawn phenomenon. Insulin analogues have improved the treatment of diabetes, eroding part of the place previously occupied by CSII, but CSII still remains the first option for patients experiencing severe hypoglycaemic episodes, high HbA1c values or marked glucose variability while being treated with optimized MDI. Furthermore CSII is better than MDI considering the effects on quality of life and the possibility to adjust insulin administration according to physical activity or food intake. CSII may be limited by cost. Present estimates suggest that CSII may be cost-effective just for patients experiencing a marked improvement in HbA1c or a decrease in severe hypoglycaemic episodes, but the effects on quality of life are difficult to measure. CSII does not merely imply wearing an external device; it requires a multidisciplinary team, intensive patient education and continuous follow up. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2002
Sten Madsbad
Abstract To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time,action profile most studies have not been able to show any improvement in overall glycaemic control with the fast-acting analogues. A reduced post-prandial increase in blood glucose has been found in all studies, whereas between 3 and 5,h after the meal and during the night an increased blood glucose level is the normal course. This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting in a long half-life with a residual activity of about 50% 24,h after injection. Insulin glargine is a peakless insulin and studies in both type 1 and type 2 diabetic patients indicate that glargine improves fasting blood glucose control and reduces the incidence of nocturnal hypoglycaemia. Surprisingly, the new fast,acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring. Copyright © 2002 John Wiley & Sons, Ltd. [source]

The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes , results of the randomized, controlled PREDICTIVEÔ 303 study

DIABETES OBESITY & METABOLISM, Issue 6 2007
L. Meneghini
The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation 303 (PREDICTIVEÔ 303) Study (n = 5604) evaluated the effectiveness of insulin detemir, a long-acting basal insulin analogue, using a simplified patient self-adjusted dosing algorithm (303 Algorithm group) compared with standard-of-care physician-driven adjustments (Standard-of-care group) in a predominantly primary care setting, over a period of 6 months. Insulin detemir was to be started once-daily as add-on therapy to any other glucose-lowering regimens or as a replacement of prestudy basal insulin in patients with type 2 diabetes. Investigator sites rather than individual patients were randomized to either the 303 Algorithm group or the Standard-of-care group. Patients from the 303 Algorithm group sites were instructed to adjust their insulin detemir dose every 3 days based on the mean of three ,adjusted' fasting plasma glucose (aFPG) values (capillary blood glucose calibrated to equivalent plasma glucose values) using a simple algorithm: mean aFPG < 80 mg/dl (<4.4 mmol/l), reduce dose by 3 U; aFPG between 80 and 110 mg/dl (4.4,6.1 mmol/l), no change; and aFPG > 110 mg/dl (>1.1 mmol/l), increase dose by 3 U. The insulin detemir dose for patients in the Standard-of-care group was adjusted by the investigator according to the standard of care. Mean A1C decreased from 8.5% at baseline to 7.9% at 26 weeks for the 303 Algorithm group and from 8.5 to 8.0% for the Standard-of-care group (p = 0.0106 for difference in A1C reduction between the two groups). Mean FPG values decreased from 175 mg/dl (9.7 mmol/l) at baseline to 141 mg/dl (7.8 mmol/l) for the 303 Algorithm group and decreased from 174 mg/dl (9.7 mmol/l) to 152 mg/dl (8.4 mmol/l) for the Standard-of-care group (p < 0.0001 for difference in FPG reduction between the two groups). Mean body weight remained the same at 26 weeks in both groups (change from baseline 0.1 and ,0.2 kg for the 303 Algorithm group and the Standard-of-care group respectively). At 26 weeks, 91% of the patients in the 303 Algorithm group and 85% of the patients in the Standard-of-care group remained on once-daily insulin detemir administration. The rates of overall hypoglycaemia (events/patient/year) decreased significantly from baseline in both groups [from 9.05 to 6.44 for the 303 Algorithm group (p = 0.0039) and from 9.53 to 4.95 for the Standard-of-care group (p < 0.0001)]. Major hypoglycaemic events were rare in both groups (0.26 events/patient/year for the 303 Algorithm group and 0.20 events/patient/year for the Standard-of-care group; p = 0.2395). In conclusion, patients in the 303 Algorithm group achieved comparable glycaemic control with higher rate of hypoglycaemia as compared with patients in the Standard-of-care group, possibly because of more aggressive insulin dose adjustments. The vast majority of the patients in both groups were effectively treated with once-daily insulin detemir therapy. The use of insulin detemir in this predominantly primary care setting achieved significant improvements in glycaemic control with minimal risk of hypoglycaemia and no weight gain. [source]

Premixed insulin treatment for type 2 diabetes: analogue or human?

DIABETES OBESITY & METABOLISM, Issue 5 2007
Alan J. Garber
The progressive nature of type 2 diabetes makes insulin initiation a necessary therapeutic step for many patients. Premixed insulin formulations containing both basal and prandial insulin (so called biphasic insulin) are often prescribed because they are superior to long- or intermediate-acting insulin in obtaining good metabolic control. In addition, they are considered as an attractive alternative to classical basal-bolus therapy as fewer daily injections are required. Premixed insulin formulations include conventional (e.g. biphasic human insulin 70/30, or 30/70 in European countries, BHI 30) and newer premixed human analogues (e.g. biphasic insulin aspart 70/30, or 30/70 in Europe, BIAsp 30; insulin lispro mix 75/25,Mix 75/25, or Mix 25/75 in Europe). Like conventional premixed human insulin, premixed insulin analogues contain a fixed proportion of soluble, rapid-acting insulin analogue, with protaminated analogue comprising the remainder. Unlike conventional premixes, analogue premixes have more physiological pharmacokinetic and therapeutically more desirable pharmacodynamic profiles than premixed human insulin. Consequently, postprandial glycaemic control is better with premixed insulin analogues than with premixed human insulin. In nontreat-to-target registration trials, the lowering of haemoglobin A1c with premixed insulin analogues was not inferior to that seen with premixed human insulin. Minor hypoglycaemia was similar for premixed analogue and premixed human insulins, while major hypoglycaemia appears to be rare with either formulation. The occurrence of adverse events, other than hypoglycaemia, was also similar between various premix insulins. The premixed insulin analogues, BIAsp 30 and Mix 75/25, like the fast-acting analogues from which they are derived, also allow flexible injection timing, relative to meal timing, thus improving adherence, compliance and quality of life compared with premixed human insulin. Overall, the evidence suggests that premixed insulin analogues are cost effective and have useful advantages over premixed human insulin for the treatment of type 2 diabetes. [source]

Insulin glargine and receptor-mediated signalling: clinical implications in treating type 2 diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2007
Derek Le Roith
Abstract Most patients with type 2 diabetes mellitus will eventually require insulin therapy to achieve or maintain adequate glycaemic control. The introduction of insulin analogues, with pharmacokinetics that more closely mimic endogenous insulin secretion, has made physiologic insulin replacement easier to achieve for many patients. However, there are also concerns regarding alteration of binding affinities for the insulin receptor (IR) or insulin-like growth factor-1 receptor (IGF-1R) may increase the mitogenic potential of some analogues. Therefore, this article will review the relevant preclinical and clinical data to assess the mitogenic potential of insulin glargine, a basal insulin analogue, compared with regular human insulin (RHI). Searches of the PubMed database were performed using terms that included ,IR,' ,insulin-like growth factor-1,' ,IGF-1R,' ,type 2 diabetes mellitus,' and ,insulin glargine.' Original articles and reviews of published literature were retrieved and reviewed. Although one study reported increased binding affinity of insulin glargine for the IGF-1R and increased mitogenic potential in cells with excess IGF-1Rs (Saos/B10 osteosarcoma cells), most in vitro binding-affinity and cell-culture studies have demonstrated behaviour of insulin glargine comparable to that of RHI for both IR and IGF-1R binding, insulin signalling, and metabolic and mitogenic potential. Currently published in vivo carcinogenic studies and human clinical trial data have shown that insulin glargine is not associated with increased risk for either cancer or the development or progression of diabetic retinopathy. Copyright © 2007 John Wiley & Sons, Ltd. [source]

An overview of insulin glargine

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S3 2002
Philip D. Home
Abstract Insulin glargine is an innovative, long-acting human insulin analogue, whose prolonged mean activity profile has no pronounced peak. Accordingly, it mimics more closely the natural physiological profile of basal endogenous insulin secretion than do traditional extended-acting insulins such as NPH insulin. As would be expected for a more satisfactory basal insulin, clinical trials comparing insulin glargine with NPH insulin show less nocturnal hypoglycaemia, improved pre-breakfast blood glucose levels, or both. Furthermore, no substantive safety concerns have emerged for insulin glargine. Thus, insulin glargine represents the first major advance in the provision of basal insulin injection therapy for people with type 1 and type 2 diabetes for over 50 years. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes1

DIABETIC MEDICINE, Issue 5 2008
T. Parkner
Abstract Aims To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid-acting insulin analogue and once daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. Methods Twenty-one patients with Type 2 diabetes treated with oral glucose-lowering agents were randomized in this two-period crossover study to an equivalent 24-h dose of continuous subcutaneous infusion of insulin aspart and subsequently once-daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded. Results On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre-injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra-subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra-subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic-only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period. Conclusions Basal continuous subcutaneous infusion of a rapid-acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once-daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. [source]

Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes

DIABETIC MEDICINE, Issue 3 2006
S. G. Ashwell
Abstract Aims To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen. Methods In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 ± 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile. Results HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference ,0.5 (95% CI ,0.7, ,0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l,1 h,1, P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l,1 h,1, P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l,1 h,1, P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001). Conclusions Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia. [source]

Recent advances in treatment of youth with Type 1 diabetes: better care through technology

DIABETIC MEDICINE, Issue 11 2001
W. V. Tamborlane
Abstract While treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid-acting insulin analogues provides a means to achieve better control of post-prandial hyperglycaemia with less late post-prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long-acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self-monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas. Diabet. Med. 18, 864,870 (2001) [source]

Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial

DIABETIC MEDICINE, Issue 11 2000
P. D. Home
SUMMARY Aims To compare the efficacy of insulin aspart, a rapid-acting insulin analogue, with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus. Methods Prospective, multi-centre, randomized, open-labelled, parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1070 adult subjects with Type 1 diabetes. Study patients were randomized 2:1 to insulin aspart or unmodified human insulin before main meals, with NPH-insulin as basal insulin. Main outcome measures were blood glucose control as assessed by HbA1c, eight-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia, and adverse events. Results After 6 months, insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 (95% confidence interval 0.03,0.22) %Hb, P < 0.02. Eight-point blood glucose profiles showed lower post-prandial glucose levels (mean baseline-adjusted ,0.6 to ,1.2 mmol/l, P < 0.01) after all main meals, but higher pre-prandial glucose levels before breakfast and dinner (0.7,0.8 mmol/l, P < 0.01) with insulin aspart. Satisfaction with treatment was significantly better in patients treated with insulin aspart (WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ) baseline-adjusted difference 2.3 (1.2,3.3) points, P < 0.001). The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 (0.59,1.18, NS). Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart (1.3 vs. 3.4% of patients, P < 0.05), as were late post-prandial (4,6 h) events (1.8 vs. 5.0% of patients, P < 0.005). Conclusions These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control, hypoglycaemia, and quality of life, in people with Type 1 diabetes mellitus. [source]

Continuous glucose monitoring system: an attractive support tool in diabetes education

EUROPEAN DIABETES NURSING, Issue 1 2005
L Saez-de-Ibarra BSc Diabetes Specialist Nurse
Abstract The study was designed to determine the usefulness of the CGMS (continuous glucose monitoring system) as a support tool in type 1 diabetes education. The CGMS is a sensor system that measures interstitial glucose levels every five minutes for three or more days, by means of a microelectrode inserted in the subcutaneous tissue. People with type 1 diabetes (n=52), who actively participated in diabetes self-management programmes, were monitored with CGMS during three to five days. Patients were selected for CGMS when unsatisfied with the glycaemic results achieved, given the effort made. Ten patients used CSII, 14 used insulin glargine plus rapid acting insulin analogue and 28 used NPH insulin plus short acting insulin. All patients used blood glucose self-monitoring, with a mean of 6.5±1.4 glucose readings per day. The CGMS register was evaluated with the patient. Mean capillary glucose during the 15 days prior to CGMS, mean capillary glucose during CGMS and mean capillary glucose during the 15 days after CGMS are compared. Discussion of the record with the patient frequently allowed detection of inappropriate solving attitudes. Mean capillary glucose dropped from 155±20mg/dL (8.60±1.11mmol/L) prior to CGMS to 143±20mg/dL (7.94±1.11mmol/L) after CGMS (p=0.000). The effectiveness of CGMS (number of patients in whom mean glucose improved) rose from 66.7% in 2001 to 70.6% in 2002, 78.9% in 2003 and 88.8% in 2004. When the patient is involved in the analysis of glucose fluctuations, CGMS is a useful tool in diabetes education that will help achieve attitude changes because of the evidence depicted by the continuous glucose record. Experience in the use of this tool by the professional will improve its effectiveness. Copyright © 2005 FEND. [source]

Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes

PEDIATRIC DIABETES, Issue 3pt2 2008
Minna Päivärinta
Background:, Insulin glargine is a long-acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes. Objective:, We evaluated the clinical course of diabetes in children and adolescents who were switched from NPH to insulin glargine. Methods:, Between August 2003 and November 2004, a total of 76 subjects were switched to glargine in our clinic, treating 340 children with type 1 diabetes. All the subjects had been receiving insulin NPH, and their serum C-peptide levels had been non-detectable for at least 1 yr. Data were collected retrospectively, and 12,18 months after the change, experiences with glargine were inquired using a questionnaire. Seven subjects (9.2%) discontinued glargine before 12 months, and seven refused to participate. Results:, Data for 62 subjects were analyzed. At the switch (0 months), their mean age was 12.7 yr (range 5.1,17.5), mean duration of diabetes was 6.7 yr (range 1.8,14.3), and mean hemoglobin A1c was (HbA1c) 9.2%. Twelve months later (+12 months), the mean HbA1c remained similar (9.2%), the proportion of long-acting insulin was smaller (47.7 vs. 58.1%; p < 0.001), and the daily insulin dose was lower (0.97 vs. 1.05 IU/kg; p < 0.001). The number of injections was lower at +12 months (17.7% with more than five injections vs. 64.5%; p < 0.001). No differences were seen in weight for height or the number of severe hypoglycemias. Most subjects who continued with glargine for ,12 months considered glargine better than NPH. Conclusions:, A switch to insulin glargine retains a similar glycemic control and does not change the number of severe hypoglycemias. [source]

Combination treatment of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus

PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2004
AN Dixon MRCP (UK) Clinical Research FellowArticle first published online: 7 DEC 200
Abstract The recently published guidelines from the National Institute for Clinical Excellence (NICE) on the management of blood glucose in type 2 diabetes and the NICE guidelines on the use of the long-acting insulin analogue, glargine, have brought to the fore the use of combination therapy of insulin with oral hypoglycaemic agents (OHAs). The NICE guidelines recommend that when a patient with type 2 diabetes is failing to achieve satisfactory glycaemic control with OHAs alone, insulin should be initiated in combination with OHAs. However, evidence for this approach is less than robust and combination treatment of OHAs with insulin remains a controversial area. This article presents the evidence for different insulin regimens in patients who have secondary failure to OHAs, including combination therapy with basal insulin. The evidence and potential drawbacks of such regimens are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source]

An Update on the Long-Acting Insulin Analogue Glargine

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2006
Henriette Thisted
However, this must be achieved with minimal risk of hypoglycaemia. Glargine is a new long-acting insulin analogue with an action profile designed to overcome this and has now been in clinical use for a number of years. In many countries glargine is widely used. Here we present an update on the clinical information available on glargine with respect to glycaemic control, the risk of hypoglycaemia and quality of life in both type 1 and type 2 diabetes. [source]

Mid- and high-ratio premix insulin analogues: potential treatment options for patients with type 2 diabetes in need of greater postprandial blood glucose control

DIABETES OBESITY & METABOLISM, Issue 2 2010
J. S. Christiansen
Some patients with type 2 diabetes continue to have high postprandial blood glucose levels on twice-daily regimens of ,low-ratio' premix insulin formulations (up to 30% rapid-acting, with 70% protracted insulin). These patients require intensified insulin therapy, which can be provided by a twice- or thrice-daily regimen of mid-ratio (50% rapid-acting and 50% protaminated intermediate-acting insulin , human or analogue) or high-ratio (70% rapid-acting and 30% protaminated insulin , analogue only) premix insulin. Alternatively, a third daily injection of low-ratio premix insulin can be added to the regimen, with the option of incorporating one or more injections of mid- or high-ratio premix as required, and as an alternative to basal,bolus therapy. How these mid- and high-ratio formulations differ from the low-ratio premix insulins is reviewed here, with the aim of identifying the role of these formulations in diabetes management. Glucose clamp studies have shown that premix analogues give serum insulin levels proportional to their percentage of rapid-acting uncomplexed insulin: the higher the proportion, the greater the maximum level reached. Other pharmacokinetic parameters were not always significantly different between the mid- and high-ratio formulations. In clinical trials, postprandial plasma glucose and glycated haemoglobin A1c (HbA1c) levels were significantly reduced with thrice-daily mid- /high-ratio premix analogue when compared with twice-daily low-ratio biphasic human insulin (BHI) 30/70 or once-daily insulin glargine. Moreover, glycaemic control with mid-/high-ratio premix analogue was found to be similar to that with a basal,bolus therapy. Mid- and high-ratio premix regimens are generally well tolerated. The frequency of minor hypoglycaemia was reportedly higher with mid- /high-ratio premix analogues than with BHI 30, but nocturnal hypoglycaemia was less frequent. Although there is little evidence that clinical outcomes with mid-ratio premix analogues are different from those with high-ratio, they are useful additions to the low-ratio formulations for the management of diabetes, and addressing postprandial hyperglycaemia in particular. [source]

Insulin therapy in type 2 diabetes: what is the evidence?

DIABETES OBESITY & METABOLISM, Issue 5 2009
Mariëlle J. P. Van Avendonk
Aim:, To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus Methods:, A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. Results:, The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long-acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long-acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal,bolus regimen seems not possible. Some studies showed that rapid-acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. Conclusion:, A once-daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years. [source]

Long-acting insulin analogues vs.

DIABETES OBESITY & METABOLISM, Issue 4 2009
NPH human insulin in type 1 diabetes.
Aim:, Basal insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human insulin or long-acting insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human insulin and each long-acting analogue. Methods:, Of 285 randomized controlled trials with a duration > 12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov, 20 met eligibility criteria (enrolling 3693 and 2485 in the long-acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed. Results:, Long-acting analogues had a small, but significant effect on HbA1c [-0.07 (,0.13; ,0.01)%; p = 0.026], in comparison with NPH human insulin. When analysing the effect of long-acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human insulin [by 0.26 (0.06;0.47) kg/m2; p = 0.012]. Long-acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01]. Conclusions:, The switch from NPH to long-acting analogues as basal insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia. [source]

Insulin analogues: an example of applied medical science

Premixed insulin treatment for type 2 diabetes: analogue or human?

Novel insulin analogues and its mitogenic potential

Appraising the mitogenicity of insulin analogues relative to human insulin,response to: Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activity in cultured cancer cells.

Insulin therapy and quality of life.

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2009
A review
Abstract Three central goals in the treatment of diabetes mellitus are (1) the avoidance of hyperglycaemia to prevent the development or progression of diabetes complications over time, (2) the avoidance of hypoglycaemia and (3) the maintenance or achievement of good quality of life. Insulin is the most powerful agent that can be used to control blood glucose levels. This article reviews the studies that have investigated the effects of different types of insulin and insulin delivery techniques on quality of life of patients with type 1 or type 2 diabetes. First, the concept of ,quality of life' (QoL) is defined and different ways of measuring QoL are explained. Secondly, the effects of different aspects of insulin therapy on QoL are reviewed: (1) the phenomenon of ,psychological insulin resistance'; (2) the effects of different types of insulin: regular insulin versus short-acting insulin analogues, long-acting insulin analogues or biphasic mixtures; (3) multiple daily injections versus pump therapy. Having multiple complications of diabetes is clearly associated with decreased QoL. Results from large studies such as the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) suggest that intensive treatment itself does not impair QoL. Recent findings further suggest that pump therapy, compared to multiple daily injections, has beneficial effects on QoL. The fact that multiple tools are used to assess QoL makes it difficult to draw conclusions regarding the effects of different types of insulin on QoL. More work on the standardization of the assessment of QoL in diabetes is urgently needed. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Insulin glargine and receptor-mediated signalling: clinical implications in treating type 2 diabetes

Continuous subcutaneous insulin infusion with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost-effectiveness

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2004
Régis Pierre Radermecker
Abstract Portable insulin infusion devices are effective and safe insulin delivery systems for managing diabetes mellitus, especially type 1 diabetes. Rapidly absorbed insulin analogues, such as insulin lispro or insulin aspart, may offer an advantage over regular human insulin for insulin pumps. Several open-label randomised crossover trials demonstrated that continuous subcutaneous insulin infusion (CSII) with insulin lispro provided a better control of postprandial hyperglycaemia and a slightly but significantly lower glycated haemoglobin level, with lower daily insulin requirement and similar or even less hypoglycaemic episodes. A CSII study comparing insulin lispro and insulin aspart demonstrated similar results with the two analogues, and better results than those with regular insulin. Because these analogues have a quicker onset and a shorter duration of action than regular insulin, one might expect an earlier and greater metabolic deterioration in case of CSII interruption, but a more rapid correction of metabolic abnormalities after insulin boluses when reactivating the pump. These expectations were confirmed in randomised protocols comparing the metabolic changes occurring during and after CSII interruption of various durations when the pump infused either insulin lispro or regular insulin. The extra cost resulting from the use of CSII and insulin analogues in diabetes management should be compensated for by better metabolic control and quality of life. In conclusion, CSII delivering fast-acting insulin analogues may be considered as one of the best methods to replace insulin in a physiological manner by mimicking meal and basal insulin requirements, without higher risk of hypoglycaemia or ketoacidosis in well-educated diabetic patients. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

A review of basal insulins

DIABETIC MEDICINE, Issue 11 2003
Anthony H. Barnett
Abstract Tight glycaemic control (ideally, HbA1c < 7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes. [source]