insulin-detemir and Diabetes-Mellitus

Insulin remains a predominant life-saving medication for type 1 and type 2 Diabetes Mellites. Natural insulin secretion limits the fluctuation of the narrow and high surge of blood glucose levels. However, imitating the same by external insulin remains a challenge as a variety of insulin analogs (rapid acting, short acting, intermediate acting and long-acting) have different pharmacokinetic (PK) and pharmacodynamic (PD) properties. Inconsistent reduction in overall hyperglycemia level and nocturnal hypoglycemia due to variable absorption time and time action profile predominantly highlights the need of revisiting the PK/PD of insulin analogs as single analog is not yet sufficed to replace internal insulin exogenously. Combination therapy with basal and prandial insulins or intensification of hypoglycemic therapy with premixed insulins are of prime importance in managing diabetes effectively, imitating the natural insulin secretion. Therefore, the knowledge of PK/PD properties might help a practitioner to design, implement and manage insulin replacement therapy effectively and averting adverse events. Present study reports the comparative analysis of PK/PD profile of various insulin analogs based on the concurrent information about clinical aspects. Moreover, study interlinks the major concerns of therapeutic efficacy of insulin analogs with their respective onset of action and duration of effectiveness and reported adverse drug reaction which explore the scope of improvement.

Topics: Diabetes Mellitus; Forecasting; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

In the past decade, there has been much advancement in oral antidiabetic agents, but few changes in insulin therapy. With the addition of the ultra-long-acting insulins, insulin glargine U300 (IGlar 300) and insulin degludec (IDeg 100 and IDeg 200), it is important to understand key aspects in the agents' clinical properties, efficacy, safety, dosing, packaging, and place in therapy.. A literature review was conducted using PubMed database and was limited to English, full-text articles published from January 2000 to January 2018. The following search terms were used: insulin glargine 300, insulin degludec, Toujeo, Tresiba, and ultra-long-acting insulin.. These agents are longer acting with sustained insulin coverage as compared with other basal insulins while having a low potential for hypoglycemia. Efficacy and safety profiles are quite good, and potential for weight gain was similar to IGlar 100.. Depending on the patient's needs, these newer agents may offer some advantages. Insulin glargine U300 and IDeg 200 are concentrated, allowing for administration of large doses by less volume, thereby theoretically improving absorption. For patients needing flexible dosing, IDeg may be beneficial. The ultra-long-acting agents may also be useful if it is suspected that the basal insulin is not lasting the entire day.

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Patient Safety; Prevalence; Weight Gain

Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine. Indeed, NPH insulin remains widely used today despite a frequent need for a twice-daily dosing and a relatively high incidence of hypoglycaemia. The early insulin analogues used post-injection precipitation (insulin glargine U100) or dimerization and albumin binding (insulin detemir) as methods of increasing therapeutic duration. These products approached a 24-hour glucose-lowering effect with decreased variability in insulin action. Newer basal insulin analogues have used up-concentration in addition to precipitation (insulin glargine U300), and multihexamer formation in addition to albumin binding (insulin degludec), to further increase duration of action and/or decrease the day-to-day variability of the glucose-lowering profile. Clinically, the major advantage of these recent analogues has been a reduction in hypoglycaemia with similar glycated haemoglobin control when compared with earlier products. Future therapies may bring clinical benefits through hepato-preferential insulin receptor binding or very long durations of action, perhaps enabling once-weekly administration and the potential for further clinical benefits.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Lente; Insulin, Long-Acting; Recombinant Proteins

The importance of glycemic control in preventing the chronic and devastating complications of diabetes is well established. Insulin administration is an important therapeutic option for managing diabetes, particularly for patients with profound insulin deficiency. Many insulin formulations are on the market, including short-acting insulin analogues, inhaled insulin, concentrated insulin, and basal insulin. Each category has a unique onset, peak, and duration of action. This article reviews the differing pharmacokinetic and pharmacodynamic properties and safety and efficacy data, and discusses the implications for clinical practice.

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Short-Acting; Insulins

Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.

Topics: Blood Glucose; Body Weight; Central Nervous System; Diabetes Mellitus; Energy Intake; Homeostasis; Humans; Hypoglycemic Agents; Insulin Detemir; Kidney; Liver; Weight Gain

Human serum albumin (HSA) has emerged as a versatile carrier for therapeutic agents, primarily for treating diabetes and cancer, improving the pharmacokinetic profile of the drug or delivering the drug to the pathogenic site addressing diseases with unmet medical needs. Market approved products include fatty acid derivatives of human insulin or the glucagon-like-1 peptide (Levemir, Tresiba, and Victoza) which bind physically to the respective binding sites of HSA thus extending their half-life. For cancer treatment, the paclitaxel albumin nanoparticle Abraxane has been approved for treating metastatic breast cancer, non-small cell lung cancer, and advanced pancreatic cancer. Finally, the albumin-binding prodrug of doxorubicin, Aldoxorubicin, which binds covalently to the cysteine-34 position of circulating albumin, is in advanced clinical trials with a registration phase 3 trial for soft tissue sarcoma initiated in Q1 2014.

Topics: Albumin-Bound Paclitaxel; Albumins; Diabetes Mellitus; Doxorubicin; Drug Carriers; Humans; Insulin Detemir; Insulin, Long-Acting; Molecular Structure; Neoplasms; Paclitaxel; Serum Albumin

Appropriate management of diabetes mellitus before a procedure or operation is important for the prevention of hypo- and hyperglycemia in the periprocedural/perioperative period. This can significantly influence glucose levels after a procedure, which in turn affects outcomes. There is a paucity of prospective trials addressing algorithms to guide adjustment of oral diabetes medications and insulin prior to a procedure. Our institution has developed guidelines that allowed us to standardize the periprocedural process for glucose management across departments. This article describes our experience with guidelines, discusses salient features of medication management, and summarizes prospective trials and expert opinion to provide recommendations for clinicians to effectively manage glucose preprocedurally for their patients with diabetes.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Practice Guidelines as Topic; Preoperative Care

Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas.. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial "closed-loop" systems mimicking the pancreatic activity have been also developed.. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.

Topics: Amino Acid Sequence; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Models, Biological; Molecular Sequence Data

Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles and provide better postprandial glucose control and less hypoglycaemia (primarily nocturnal and severe hypoglycaemia in type 1 diabetes mellitus) than regular insulin. Insulin glulisine is a new rapid-acting analogue and has characteristics nearly identical to those of its predecessors. Insulin glargine was the first basal analogue approved for clinical use and has shown better fasting glucose control and less risk of hypoglycaemia than conventional human neutral protamine Hagedorn (NPH) insulin. More recent studies have indicated that insulin glargine may not be truly 'peakless' at higher doses and that the adjustment of dose timing and frequency may have favourable effects on the risk of hypoglycaemia and the duration of the effect. Insulin detemir is a new basal insulin analogue with superiority to NPH insulin similar to that demonstrated by insulin glargine, though its duration of action appears to be shorter. The intraindividual variability in the response to a given dose is lower for insulin detemir than for both NPH insulin and insulin glargine. The clinical significance of this finding is not clear, though it may contribute to the lower rate of hypoglycaemia seen with insulin detemir. A number of 'alternative routes' of insulin administration have been studied, the most promising of which has been the pulmonary route. The time-action profile of inhaled insulins is generally characterized by a rapid onset of action similar to those of rapid-acting analogues and a slightly protracted duration of action similar to that of regular insulin. Inhaled insulin is similar to regular insulin with respect to efficacy and safety, though small reversible changes in pulmonary function have been noted. For technical and practical reasons, other alternative routes have generally not met with clinical success.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus; Drug Administration Routes; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a duration >or=24 h, (2) a single subcutaneous dose of glargine/detemir was used, and (3) area under the curve for insulin concentrations or glucose infusion rates were calculated.

Topics: Amino Acid Sequence; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Molecular Sequence Data

Weight gain is often perceived as inevitable with insulin therapy, particularly as we strive for tight glycaemic control and are using increasingly proactive insulin titration regimes. The United Kingdom Prospective Diabetes Study documented that weight gain occurs most rapidly soon after insulin therapy is first initiated. The timing of this side effect is particularly undesirable, as weight gain may interfere with patients' adjustment to insulin therapy and may undermine appropriate diabetes self-management behaviours. Until recently, many patients had little alternative other than to accept unwanted weight gain if they were to achieve sufficient glycaemic control to reduce risk of chronic complications of diabetes. Insulin detemir is a novel basal insulin analogue that has consistently been shown in randomized, controlled trials to have a weight-sparing effect (i.e. weight loss or reduced weight gain compared with other insulins) in both type 1 and type 2 diabetes. Indeed, unlike neutral protamine Hagedorn (NPH) insulin, the weight-sparing effect of insulin detemir appears to be most prominent in people who are the most obese. The mechanisms behind the weight-sparing effect of insulin detemir are still being clarified. Reduced risk of hypoglycaemia with insulin detemir, coupled with a more consistent and reliable delivery of the desired dose than is available with traditional basal insulin, such as NPH, has been proposed to minimize defensive snacking by patients, and help to limit weight gain. However, even if this was proven, it would be unlikely to fully explain the weight-sparing effect of insulin detemir. Two additional theories have been put forward. One suggests that due to its novel method of prolonging action via acylation and albumin binding, insulin detemir may differentially influence hepatocytes more than peripheral tissues, thus effectively suppressing hepatic glucose output without promoting lipogenesis in the periphery. The second theory suggests that insulin detemir may be more effective than human insulin in communicating satiety signals within the central nervous system. Further clarification of these hypotheses is required.

Topics: Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Weight Gain

While the advantages of the two basal insulin analogues, glargine and detemir, over neutral protamine Hagedorn are well established, the relative merit of the two compared with each other has been a matter of some controversy. The two analogues are popularly perceived to differ from each other in their pharmacodynamic (PD) profiles, in particular with regard to 'flatness' and duration of action. The aim of this review, therefore, is to give a complete overview on the available PD data of both analogues as derived with the glucose clamp technique. In order to improve parity across studies, a common definition for duration of action (time from injection to plasma glucose >8.3 mmol/l) was applied and study data were recalculated when necessary. Despite differences in methodological details, the results of most clamp studies were very consistent. Glargine and detemir both typically show a gentle rise and fall in glucose-lowering action over time. Duration of action with both analogues is dose dependent, but in the clinically relevant range of 0.35-0.8 U/kg it is close to 24 h in people with type 1 diabetes and in excess of this in people with type 2 diabetes. While both analogues seem to be very similar with regard to the mean shape of their PD profile and duration of action, detemir shows less within-subject variability in its metabolic effect. These findings in experimental glucose clamp studies are consistent with observations in clinical trials and support routine once daily use with either analogue, in particular in people with type 2 diabetes.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Male; Treatment Outcome

Insulin analogues, developed by molecular engineering, have structural changes in the A and B insulin chains. These modifications change their action profile, rendering insulin replacement closer to physiology. Rapid acting analogues like lispro, aspart and glulisine, are absorbed rapidly from the subcutaneous tissue to the circulation. In addition, two long acting insulin analogues have been developed: glargine and detemir. The combination of a long acting insulin, to maintain baseline levels, and multiple daily doses of a rapid acting analogue are the mainstay of basal-bolus therapy. Multiples studies have compared human insulin (NPH and regular) with insulin analogues in patients with type 1 or 2 diabetes mellitus, showing an improvement in the metabolic control, fewer hypoglycemic events and better quality of life. In summary, insulin analogues offer new therapeutic options and allow an individualized intensive treatment.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Lispro; Insulin Secretion; Insulin, Long-Acting

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. Insulin detemir is 98-99% albumin bound in plasma. It has a more predictable glucose-lowering effect than NPH insulin or insulin glargin. There is a dose-response relationship, but at the dose of 0.4 units/kg (an average normal dose), the duration of action reaches nearly 24 h. Therefore, detemir, most often injected once per day at bedtime, seems to be the ideal basal insulin in the basal-prandial therapy for type 1 diabetic patients. The boli of insulin, in order to cover shown to reduce the risk of (severe) hypoglycaemias, particularly nocturnal (up to 50 %). Fasting hyperglycaemia is often lower, but it is not necessarily true for glycated haemoglobin. In addition, detemir has been associated with less weight gain than NPH insulin. Detemir is well tolerated and no specific safety concerns have been raised.

Topics: Delayed-Action Preparations; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting

Patients with diabetes are at increased risk of mortality and morbidity from micro- and macrovascular complications (1, 2). Landmark studies in type 1 and 2 diabetes have clearly shown that improved glycemic control leads to better outcomes (3-6). With the introduction of the General Medical Service contract, the England and Wales National Service Framework, and other schemes, there is a national drive to improve control in patients with diabetes. The treatment of diabetes was revolutionized shortly after the turn of the 20th century by the extraction and purification of insulin. Since methods to protract (i.e., prolong) the action of insulin were developed in the 1930s, little changed in this technology until the turn of this century. At this time there was renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, and so technology advanced again. Two new basal insulin analogues have come to the market: insulin glargine, which has been widely used for some years now, and detemir. This review describes the novel method of protraction employed by insulin detemir, discusses the possible therapeutic benefits of this method of protraction, and describes the findings of studies comparing insulin detemir with other currently available basal insulin preparations. It is not the intention of this paper to be a review of all the currently available long-acting insulin analogues.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

The treatment of diabetes was revolutionised shortly after the turn of the twentieth century by the extraction and purification of insulin. Methods to protract (i.e. prolong) the action of insulin were developed in the 1930s; little changed in the technology of insulin protraction until the turn of this century when, with renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, technology advanced again. Two new long-acting insulin analogues have come to the market; some may be familiar with insulin glargine, which has been widely used for some years now. This review attempts to describe the novel method of protraction that insulin detemir (launched last summer) employs by albumin binding, to discuss the possible therapeutic benefits of this method of protraction and to describe the findings of studies comparing insulin detemir with other currently available long-acting insulin preparations. The intention of this article is not to review all of the currently available long-acting insulin analogues.

Topics: Delayed-Action Preparations; Diabetes Mellitus; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting

The importance of strict glycaemic control in reducing diabetes-related outcomes is well recognised. Yet, despite the range of available treatment options, clinical experience suggests that individuals with diabetes frequently fail to achieve good glucose control. Instead, patients often have poorly controlled, unpredictable blood glucose levels. In insulin-treated patients, one of the reasons for this may be the inherently variable action of exogenously injected insulin. For example, the currently available longer-lasting insulin preparations that aim to provide a continuous basal level of circulating insulin are associated with markedly variable action both between and within subjects. Unpredictable insulin action contributes to variable blood glucose control, which in addition to increasing the risk of hypoglycaemia has also been shown to be an independent risk factor for mortality. It is hoped that advances in longer-lasting insulin preparations will provide significant benefits to patients, improving control and reducing variability. A new, long-lasting analogue, insulin detemir, has been shown to be significantly less variable than other basal insulin preparations in pharmacological and clinical studies. The improved predictability in insulin response offered by insulin detemir may be associated with a number of clinical benefits including a reduction in hypoglycaemia and weight gain.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Postprandial Period

Tight glycaemic control is essential for reducing the risk of long-term diabetic complications in people with type I or II diabetes. Intensive blood-glucose control attempts to normalise both pre- and postprandial glycaemia, while avoiding severe hypoglycaemia. A basal insulin, providing a low level of insulin to cover postprandial and overnight fasting periods, is central to intensive blood-glucose control. However, hypoglycaemia, particularly nocturnal hypoglycaemia, is a major treatment-related complication of therapy with most basal insulins currently available for use in clinical practice. This is a result of pronounced peaks in absorption, which lead to inappropriate hyperinsulinaemia following evening administration, and especially poorly reproducible pharmacokinetic profiles when injected subcutaneously. Indeed, for many patients and health-care providers, concern around hypoglycaemia forms a critical barrier to the attainment of tight glycaemic control. Insulin detemir is a novel long-acting analogue of human insulin designed to overcome these practical limitations. Clinical evidence from comparative studies with NPH insulin shows that insulin detemir provides a consistent and clinically relevant reduction in hypoglycaemic risk, especially for nocturnal events, at equivalent or better levels of glycaemic control.

Topics: Blood Glucose; Circadian Rhythm; Delayed-Action Preparations; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

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.

Topics: Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Parenteral; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Amino Acid Sequence; Animals; Blood Glucose; Carrier Proteins; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Molecular Sequence Data; Solubility

Landmark studies have confirmed the importance of intensified insulin treatment for minimizing long-term diabetic complications. Human insulin is still first-line treatment. However, even the most intensive of human insulin-based regimens can only poorly reproduce physiologically desirable insulin release, which includes rapid outbursts of insulin at mealtimes coupled with relatively low and stable basal levels between meals. Encouragingly, there are now four available or soon-to-be-available insulin analogues that offer the potential for more physiological insulin profiles. Insulin lispro and insulin aspart are rapid-acting insulin analogues intended for immediate pre-meal administration in type 1 or type 2 diabetes. Compared with injected human insulin, they improve post-prandial glucose control and reduce late post-meal and night-time hypoglycaemic episodes. Two basal insulin analogues, insulin glargine and insulin detemir, have also shown beneficial profiles with regard to night-time hypoglycaemia.Some, but not all, studies with the two rapid-acting insulins have shown improvement in overall glucose control, as assessed by HbA(1c), in comparison to human insulin. These results are encouraging and provide hope that entirely analogue-based regimens may improve overall glycaemic control and ease of use of insulin.

Topics: Carrier Proteins; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Topics: Carrier Proteins; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Approval; Drug Therapy, Combination; Europe; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; United States

To investigate the effects of insulin detemir in dogs with diabetes mellitus.. Prospective, uncontrolled clinical trial.. 10 client-owned dogs with naturally occurring diabetes mellitus.. Dogs were treated with insulin detemir SC every 12 hours for 6 months. Follow-up evaluations were done at 1, 2, 4, 12, and 24 weeks and included evaluation of clinical signs and measurement of blood glucose concentration curves and serum fructosamine concentrations.. Insulin detemir administration resulted in a significant decrease in blood glucose and serum fructosamine concentrations at 6 months, compared with pretreatment values. Median insulin dosage at the end of the study was 0.12 U/kg (0.055 U/lb; range, 0.05 to 0.34 U/kg [0.023 to 0.155 U/lb], SC, q 12 h). Hypoglycemia was identified in 22% (10/45) of the blood glucose concentration curves, and 6 episodes of clinical hypoglycemia in 4 dogs were recorded. A subjective improvement in clinical signs was observed in all dogs during the 6-month study period. On the basis of clinical signs and blood glucose concentration curves, efficacy of insulin detemir at the end of the study was considered good in 5 dogs, moderate in 3, and poor in 2.. Results suggested that SC injection of insulin detemir every 12 hours may be a viable treatment for diabetes mellitus in dogs. Insulin detemir dosages were lower than reported dosages of other insulin types needed to maintain glycemic control, suggesting that insulin detemir should be used with caution, especially in small dogs.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Female; Hypoglycemic Agents; Insulin Detemir; Male

The aim of this study was to determine if once daily insulin detemir reverses decline in weight and lung function in patients with cystic fibrosis (CF). 12 patients with early insulin deficiency and six with CF related diabetes (aged 7.2-18.1 years) were treated for a median of 0.8 years. Changes in weight and lung function following treatment were compared to pretreatment changes. Before treatment, the change in weight SD score (ΔWtSDS), percentage of predicted forced expiratory volume in 1 s (Δ%FEV(1)) and percentage of predicted forced vital capacity (Δ%FVC) declined in the whole study population (-0.45±0.38, -7.9±12.8%, -5.8±14.3%) and in the subgroup with early insulin deficiency (-0.41±0.43, -9.8±9.3%, -6.8±10.3%). Following treatment with insulin ΔWtSDS, Δ%FEV(1) and Δ%FVC significantly improved in the whole study population (+0.18±0.29 SDS, p=0.0001; +3.7±10.6%, p=0.007; +5.2±12.7%, p=0.013) and in patients with early insulin deficiency (+0.22±0.31 SDS, p=0.003; +5.3±11.5%, p=0.004; +5.8±13.4%, p=0.024). Randomised controlled trials are now needed.

Topics: Adolescent; Blood Glucose; Blood Glucose Self-Monitoring; Child; Cystic Fibrosis; Diabetes Mellitus; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Prediabetic State; Treatment Outcome; Vital Capacity; Weight Gain

The aim of the PREDICTIVE study, a large, multinational observational trial, was to evaluate the efficacy and safety of insulin detemir (IDet) in routine clinical practice.. Twelve-week follow-up data from patients with type 1 (T1D) or type 2 (T2D) diabetes in the European cohort switched from once (qd) or twice (bid) daily insulin glargine (IGlarg) (+/-oral antidiabetic therapy) to qd IDet in a basal-bolus regimen. End-points, assessed from patient recall/diaries, included incidence of serious adverse drug reactions, glycaemic parameters, hypoglycaemia and weight change.. The analysis included 1285 patients with T1D (n = 508) or T2D (n = 777). At 12 weeks, glycosylated haemoglobin (HbA1c) was significantly reduced (qd IGlarg to qd IDet: T1D, -0.47%; T2D, -0.51%; p < 0.0001 for both; bid IGlarg to qd IDet: T1D, -0.31%; T2D, -0.89%, p < 0.05 for both). Fasting blood glucose (FBG) and FBG variability were also reduced. Reductions in overall, major and nocturnal hypoglycaemic events were observed after switching from qd IGlarg to qd IDet (overall, T1D, 39.7-18.85 episodes/patient-year; overall, T2D, 11.57-2.99 episodes/patient-year, p < 0.0001 for both). Similar reductions were observed in bid IGlarg to qd IDet patients. Mean weight change was -0.3 to -0.4 kg across patient groups.. Switching from IGlarg to qd IDet was associated with improvements in glycaemic parameters with no associated increase in hypoglycaemic episodes or weight gain.. Patients with T1D and T2D may be switched from IGlarg to qd IDet as part of a basal-bolus regimen.

Topics: Adult; Aged; Cohort Studies; Diabetes Mellitus; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes.. Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins.. Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

Topics: Blood Glucose; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin Detemir; Insulin, Long-Acting; Perinatal Death; Pregnancy; Pregnant Women; Prospective Studies

To evaluate the effectiveness of the different insulin therapies on obstetrics-fetal outcomes in women with pregestational diabetes mellitus. We enrolled 147 pregnant women with pre-existing type 1 or 2 diabetes mellitus. Clinical and biochemical parameters were analysed in relation to obstetric and fetal outcomes. 14.2% received treatment with Neutral Protamine Hagedorn insulin and short-acting insulin analogues; 19% with premixed human insulin; 40.1% with insulin glargine and lispro, 6.2% with detemir and aspart and 20% with continuous subcutaneous insulin infusion. All 5 types of treatment achieved a reduction of the mean HbA1c during pregnancy (p = 0.01). Pre-pregnancy care was carried out for 48% of patients. We found no statistically significant differences between the different insulin therapies and the obstetric-fetal outcomes. In conclusión, the different insulin therapies used in patients with pregestational diabetes mellitus does not seem to affect obstetric-fetal outcomes.

Topics: Adult; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Drug Combinations; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Pregnancy; Pregnancy Outcome

Glargine and detemir insulin are the two most commonly prescribed basal insulin analogues for the ambulatory and inpatient management of diabetes. The efficacy and safety of basal insulin analogues in the hospital setting has not been established.. This observational study compared differences in glycemic control and outcomes in non-intensive care unit patients with blood glucose (BG) >140 mg/dL who were treated with glargine or detemir, between January 1, 2012, and September 30, 2015, in two academic centers.. Among 6,245 medical and surgical patients with hyperglycemia, 5,749 received one or more doses of glargine, and 496 patients received detemir during the hospital stay. There were no differences in the mean daily BG (glargine, 182 ± 46 mg/dL vs. detemir, 180 ± 44 mg/dL; P = .70). There were no differences in mortality, hospital complications, or re-admissions between groups (all, P>.05). After adjusting for potential confounders, there was no statistically significant difference in hypoglycemia rates between treatment groups. Patients treated with detemir required higher total daily basal insulin doses (0.27 ± 0.16 units/kg/day vs. 0.22 ± 0.15 units/kg/day; P<.001). Glargine-treated patients had statistically longer length of stay; however, this difference may not be clinically relevant (6.8 ± 7.4 days vs. 6.0 ± 6.3 days; P<.001).. Our study indicates that treatment with glargine and detemir results in similar inpatient glycemic control in general medicine and surgery patients. Detemir treatment was associated with higher daily basal insulin dose and number of injections. A prospective randomized study is needed to confirm these findings.. BG = blood glucose BMI = body mass index CI = confidence interval eGFR = estimated glomerular filtration rate HbA1c = glycated hemoglobin ICD-9 = International Classification of Diseases, ninth revision ICU = intensive care unit IQR = interquartile range LOS = length-of-stay OR = odd ratio.

Topics: Aged; Blood Glucose; Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Inpatients; Insulin Detemir; Insulin Glargine; Length of Stay; Male; Middle Aged

The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.. All persons aged 18-65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006-2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.. A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040).. Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults. KEY MESSAGES The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear. Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin. Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Topics: Adult; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; Young Adult

There are a lack of data regarding the effect of basal insulin analogues on rates of events like congenital malformation and perinatal mortality in diabetic pregnancy.. The present study is a prospective, non-interventional, multicentre cohort study conducted in seven countries, designed to assess the safety of insulin detemir during pregnancy, and to monitor the health status of resulting infants (exposed in utero) up to 1 year of age. The study population includes women with type 1 or type 2 diabetes, who are pregnant and being treated with insulin. Data will be collected in the context of routine practice. The primary endpoint is the proportion of pregnancies in women treated with insulin detemir, compared with other basal insulin regimens, which do not result in any of the following events: major congenital malformations, perinatal death or neonatal death. A sample size of 3075 pregnancies was calculated to provide an 80% power to detect a difference of 3.5% between groups in the primary endpoint at a 5% level.. The study will also examine other important maternal endpoints (e.g., incidences of severe hypoglycaemia and pre-eclampsia) and perinatal outcomes such as overweight neonates, as well as infant outcomes at 1 year of age. It has a fixed recruitment period from 2013 to 2018, enrolling all eligible patients, and is expected to inform future prescribing with basal insulins in diabetic pregnancy.. ClinicalTrials.gov: NCT01892319 (date registered: 27.06.2013).

Topics: Abnormalities, Drug-Induced; Adult; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin Detemir; Perinatal Death; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Research Design

A fatigued 8-year-old boy was found to have sideroblastic anaemia (haemoglobin 7.8 g/dL) which over time became transfusion dependent. Subtle neurological dysfunction, initially manifesting as mild spastic diplegia, was slowly progressive and ultimately led to wheelchair dependence. Elevated plasma lactate and urinary 3-methylglutaconate led to a muscle biopsy which confirmed partial complex IV deficiency. PCR in leucocytes and muscle was negative for mitochondrial DNA (mtDNA) deletions. Faltering growth prompted an insulin tolerance test which confirmed growth hormone sufficiency and adrenal insufficiency. Plasma renin was elevated and adrenal androgens were low, suggesting primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy was initiated. A renal tubular Fanconi syndrome and diabetes mellitus developed subsequently. Sideroblastic anaemia and primary adrenal insufficiency, both individually and collectively, are associated with mtDNA deletion; however, absence of the same does not exclude the possibility that sideroblastic anaemia and primary adrenal insufficiency are of mitochondrial origin.

Topics: Adrenal Insufficiency; Anemia, Sideroblastic; Child; Developmental Disabilities; Diabetes Mellitus; Disabled Children; DNA, Mitochondrial; Fanconi Syndrome; Fatigue; Fructosamine; Glucocorticoids; Hormone Replacement Therapy; Humans; Hypoglycemic Agents; Insulin Detemir; Male; Mineralocorticoids; Treatment Outcome

Topics: Animals; Biosimilar Pharmaceuticals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diabetes Mellitus; Dogs; History, 20th Century; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Swine

To evaluate the dose and frequency of insulin detemir for patients with diabetes mellitus undergoing conversion from insulin glargine to insulin detemir, and to assess glycemic control, weight gain, and risk of hypoglycemia after converting to insulin detemir.. Retrospective medical record review.. Large academic medical center.. Thirty-one patients with type 1 (10 patients) or type 2 (21 patients) diabetes who were converted from insulin glargine to insulin detemir by usual practice between January 1, 2006, and March 3, 2007, after an Iowa Medicaid formulary switch.. Data were collected for 12 months after conversion from insulin glargine to insulin detemir. No significant change in mean basal insulin dose was noted in patients with type 1 diabetes at the end of 12 months (insulin detemir 31.1 units/day vs baseline insulin glargine 32.0 units/day, p=0.89; insulin detemir 0.41 unit/kg/day vs baseline insulin glargine 0.42 unit/kg/day, p=0.91). In patients with type 2 diabetes, however, the mean basal insulin dose was significantly higher with insulin detemir compared with baseline insulin glargine (74.2 vs 55.8 units/day, p=0.002; 0.68 vs 0.48 unit/kg/day, p=0.001) at the end of 12 months. Twice-daily administration was required in a higher proportion of patients receiving insulin detemir (15 patients [48%]) at 12 months compared with insulin glargine (4 patients [13%]) at baseline (p=0.043). A significant change in hemoglobin A(1c) was not observed in patients with type 1 diabetes (9.7% with insulin detemir vs 9.3% with insulin glargine, p=0.41) or type 2 diabetes (9.4% with insulin detemir vs 9.7% with insulin glargine at baseline, p=0.57) despite the use of higher insulin detemir doses in patients with type 2 diabetes. No significant differences in weight or frequency of hypoglycemia were noted.. Treatment with insulin detemir appears to require more frequent administration and higher insulin doses compared with insulin glargine in patients with type 2 diabetes, with 33% higher doses, on average, observed in this study. These findings suggest that a unit-for-unit conversion from insulin glargine to insulin detemir, as suggested by the manufacturer of insulin detemir, may not be adequate in patients with type 2 diabetes.

Topics: Adult; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Substitution; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

Diabetes is often associated with pituitary-dependent hyperadrenocorticism (PDH). Hypercortisolism causes insulin resistance and affects β-cell function. The purpose of this study was to test if daily administration of a long-acting insulin analogue during the first month of anti-PDH treatment can prevent progress to diabetes in these animals. Twenty-six PDH dogs were divided into three groups: one group with glycaemia <5.83 mmol/L and two groups with glycaemia >5.83 mmol/L and <9.35 mmol/L, one of which received insulin detemir during 4 months. Dogs with glycaemia <5.83 mmol/L and those with glycaemia >5.83 mmol/L which received insulin did not develop diabetes. In the non-insulin group, 6/7 dogs developed diabetes after the third month. There is a 13-fold higher risk of diabetes in dogs with glycaemia >5.83 mmol/L and no insulin treatment. Administering insulin detemir to dogs with PDH and glycaemia >5.83 mmol/L could prevent progression to diabetes.

Topics: Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Blood Glucose; Cholesterol; Diabetes Mellitus; Dog Diseases; Dogs; Female; Insulin; Insulin Detemir; Insulin, Long-Acting; Triglycerides

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines has yet to be determined. Eight animals were used in our study (three normal and five insulin dependent diabetic dogs). Time-action profiles of insulin detemir were monitored in normal dogs using an artificial pancreas apparatus under euglycemic condition. Blood sampling was performed at 2h intervals post feeding, with insulin administration, in insulin dependent diabetic dogs. Time-action profiles of insulin detemir, in normal dogs, demonstrated that insulin detemir is a long-lasting preparation similar to what has been observed in humans. A pronounced peak was detected at 8-10h while the glucose-lowering effect lasted for over 24h after insulin injection, thus illustrating its longer prolonged peak activity time. Furthermore, intensive glycemic control was achieved with insulin detemir in insulin dependent diabetic dogs, using a lower dosage than NPH insulin and insulin glargine therapeutic doses. Our results indicate that insulin detemir has a greater effect than either NPH insulin or insulin glargine in canines, requiring a lower dose than either insulin preparation. However, using insulin detemir also carries a higher risk of inducing hypoglycemia as compared to either NPH insulin or insulin glargine.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Female; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male

Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect.. Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated. In cross-over fashion, 23 patients were treated with glargine plus rapid-acting insulin analogues, and similar doses of human NPH and rapid-acting insulin. For comparison, eight patients were treated with insulin detemir (Levemir) and human NPH. MCF-7 cells were incubated with 10% serum and proliferation was assessed after 72 hours.. Serum containing insulin glargine was 1.11(95% CI 1.05-1.18) fold more mitogenic than human insulin-containing serum (p < 0.005); mitogenicity of serum containing detemir was 0.99(95% CI 0.98-1.02) fold that of human insulin-containing serum.. The serum of diabetic patients was slightly stronger mitogenic when using glargine as compared to human insulin or detemir for treatment.

Topics: Breast Neoplasms; C-Peptide; Cell Line, Tumor; Cells; Chemotactic Factors; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pilot Projects; Risk Factors

Topics: Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Eating; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Patient Education as Topic

Topics: Aged; Anaphylaxis; Diabetes Mellitus; Drug Hypersensitivity; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Treatment Outcome

Easy-to-use insulin devices are an important tool in the treatment of diabetes. In this study, injection force requirements and dosage scale displays were evaluated for NovoPen 3 and NovoPen 4 (both from Novo Nordisk A/S, Copenhagen, Denmark).. To simulate 5 years of expected lifetime usage, 5,475 injections were performed automatically. Before and after lifetime testing, the force required to expel 60 U of insulin from NovoPen 3 and NovoPen 4 with 30-gauge or 31-gauge needles was measured. To compare dosage scale displays, digital images of multiple settings were made, and the total inked areas of digits were converted to mm(2).. At baseline, the mean +/- SD injection force of NovoPen 4 was 9.14 +/- 0.87 N and 16.55 +/- 1.17 N, which was significantly lower (P < 0.001) than for NovoPen 3, at 18.36 +/- 1.06 N and 29.81 +/- 1.26 N, with the 30-gauge and 31-gauge needle, respectively. After simulated lifetime testing, mean +/- SD injection force was 10.93 +/- 0.77 N and 17.77 +/- 1.14 N for NovoPen 4, which was significantly lower than the injection force of 18.54 +/- 0.94 N and 31.69 +/- 1.98 N for NovoPen 3 (P < 0.001). The mean dosage scale digit size was 1.63 mm(2) for NovoPen 3 and 7.82 mm(2) for NovoPen 4, with a mean difference of 6.19 mm(2). The display for NovoPen 4 was 4.74 times larger (P < 0.001).. The mean injection force required to operate NovoPen 4 was reduced up to 50% compared with NovoPen 3 (P < 0.001), and the mean dosage display for NovoPen 4 was over four times larger than for NovoPen 3 (P < 0.001). Based on these findings, patients with diabetes who have manual or visual impairment should find it easier to dose insulin with NovoPen 4.

Topics: Confidence Intervals; Diabetes Mellitus; Drug Delivery Systems; Humans; Hypoglycemic Agents; Image Processing, Computer-Assisted; Injections; Insulin; Insulin Detemir; Insulin, Long-Acting; Insulin, Regular, Pork; Regression Analysis; Robotics

PREDICTIVEtrade mark (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, observational study assessing the safety and efficacy of insulin detemir. We report the study design, population characteristics and baseline observations, including cross-sectional analysis, from 19 911 patients with type 1 or 2 diabetes.. Patients with type 1 or 2 diabetes requiring basal insulin are prescribed insulin detemir and followed up for 12-52 weeks. Data on demographics, haemoglobin A(1c) (HbA(1c)), fasting glucose, within-subject fasting glucose variability and weight are collected from patient records (and/or recall for hypoglycaemia). A negative binomial distribution model is used to assess the influence of predictive/confounding variables on hypoglycaemic episodes in insulin-treated patients at baseline. Multi-factorial analysis of covariance is used to evaluate the association of the variables with current body weight and within-subject fasting glucose variability.. Total hypoglycaemic episodes in the 4 weeks prior to study start were 47.5 per patient-year in patients with type 1 and 9.2 per patient-year in patients with type 2 diabetes. The frequency of hypoglycaemia in insulin-treated patients showed a significant, positive association with duration of diabetes, number of insulin injections and fasting glucose variability but was inversely related to HbA(1c), fasting glucose and body mass index. Weight showed a significant positive association with gender (male > female) and insulin dosage. Weight was also positively associated with fasting glucose variability in patients with type 1 diabetes, and age and number of injections in patients with type 2 diabetes.. These baseline data showed that, in addition to the established relationship with intensive treatment and HbA(1c), frequency of hypoglycaemia was positively associated with fasting glucose variability. Follow-up data from PREDICTIVE will provide insights on insulin detemir in diabetes management.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Sex Factors; Treatment Outcome

Topics: Cost of Illness; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome

To examine patient-reported perceptions of insulin detemir (Levemirt) as treatment for diabetes and report information back to prescribing physicians.. This cross-sectional survey with a convenience population involves physicians identifying patients appropriate for this treatment and providing them with study information. Patients voluntarily responded to a baseline survey prior to medication use and surveys at approximately 30 and 60 days following treatment initiation using interactive voice response (IVR) technology. Questions were designed by the medical group on the study team to measure patients' perceptions regarding blood sugar control, confidence in avoiding symptoms and medication satisfaction with insulin detemir. Questions were not drawn from a tested survey instrument, but do maintain face validity. Prescribing physicians received an individual report summarizing the patient's responses.. In total, 586 adults completed the study. Average age was 59 years; 64% female. After an average of 35 days and 72 days using insulin detemir, patients could more easily judge blood sugar levels (n = 586; average 6.6 and 7.0 out of 10 (10 = much easier) at each follow-up, respectively) and keep good blood sugar control (n = 586; 6.7 and 7.0). With insulin detemir, patients who used a prior insulin (n = 414) felt more confident about avoiding symptoms of hypoglycemia with an average rating of 6.8 out of 10 after the first month and 7.1 out of 10 (10 = much more confident) after the second month. They (n = 414) also felt more confident in avoiding low blood sugars at night with average ratings of 7.3 after both the first and second months with insulin detemir. Thirty-one percent of the prior insulin users (n = 414) also reported weight loss, 58% reported no change, 11% gained weight after the second month with insulin detemir. Satisfaction with insulin detemir among all patients (n = 586) averaged 7.9 out of 10 at both months 1 and 2.. With insulin detemir, patients felt more confident about managing blood sugar levels, tended not to gain weight, and were quite satisfied. The authors recognize that the results are not generalizable to or representative of all patients using insulin detemir due to potential patient selection bias. In addition, the results reflect patients' self-reported impressions which were not confirmed through any objective clinical measures. However, the individual patient data collected through the surveys can help physicians monitor patients' perceptions and promote discussions about treatment with patients.

Topics: Aged; Blood Glucose; Cross-Sectional Studies; Data Collection; Diabetes Mellitus; Female; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Patients; Telephone

In 2004, a new insulin analogue was launched, Detemir insulin (Levemir). Detemir insulin is a long acting insulin and has a lower within-subject variability in comparison with other insulins. The recently published results of the CARDS study (atorvastatin treatment) also emphasize the need for a more aggressive attitude toward cardiovascular risk in diabetics even if LDL-cholesterol values are not particularly elevated. We will end this short review discussing the future of the inhibitor of GLP-1 degradation which in addition to a modest hypoglycaemic effect seems to be able to prevent apoptosis of insulin producing beta cells.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting

Topics: Diabetes Mellitus; Europe; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting; Marketing; Multicenter Studies as Topic; Observation; Product Surveillance, Postmarketing; Public Policy; Randomized Controlled Trials as Topic; United Kingdom

Insulin detemir (Levemir) is a soluble long acting human insulin analogue acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged metabolic effect (up to 24 hours) with low variability. Indeed, in patients with type 1 or type 2 diabetes mellitus, insulin detemir has a more predictable, protracted and consistent effect, with less intrapatient variability in glycaemic control (particularly fasting plasma glucose levels), compared with NPH (Neutral Protamine Hagedorn) insulin. Insulin detemir, is at least as effective as NPH insulin in maintaining overall glycaemic control, with a lower risk of nocturnal hypoglycaemia. It also provides the additional benefit of less body weight gain as compared to other basal insulins. Levemir, presented in cartridges for the pen device NovoPen 3 and administered preferably at bedtime (if necessary morning and evening), is a promising new option for basal insulin therapy in diabetic patients, especially those on a basal-bolus scheme.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting

Topics: Animals; Delayed-Action Preparations; Diabetes Mellitus; Glycemic Index; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Patient Education as Topic

Development of the insulin analogues has made it possible to reproduce much more accurately the physiologic insulin profiles seen in people who do not have diabetes. The rapidacting analogues, such as insulin aspart and insulin lispro, offer improved postprandial glycemic control and reduced risk of hypoglycemia. The long-acting analogues, such as insulin glargine and insulin detemir, mimic the insulin secretory profile of basal insulin. Together, they approximate physiologic insulin secretion.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin Secretion; Insulin, Long-Acting