Detemir Research Articles

Hemochromatosis and Cystic Fibrosis Carriers Identify Risk for GLP-1 Agonist Associated Pancreatitis

GLP-1 agonists are widely used antidiabetic agents. Among their potential associated side effects is acute pancreatitis (AP). Its exact prevalence is unknown as are known predictors for its incidence. We present two cases that suggest that carrier states for hemochromatosis (HC) and cystic fibrosis (CF) are risk factors for GLP-1 agonist associated AP. Case 1 is a 39 year old Caucasian lady with type 2 diabetes diagnosed 2 years ago. She has morbid obesity, hypothyroidism and NAFLD. She had a history of symptomatic AP to liraglutide (Victoza), exenatide (Byetta), dulaglutide and sitagliptin. She is currently managed with Degludec insulin, repagnilide, metformin and prn Lispro insulin with a current HBA1c of 6.5. Work up for mild transaminitis and prior elevated ferritin revealed she is a heterozygous carrier for the C282Y HC mutation despite currently having normal ferrokinetic profile. Her ongoing glycemic care is now without any further use of GLP-1 analogs nor DPP-4 inhibitors. Case 2 is a 62 year old Caucasian lady with type 2 diabetes diagnosed 8 years ago. She has hypertension, hypercholesterolemia and sleep apnea. She had a history of developing symptomatic AP to exenatide ER (Bydureon), dulaglutide and liraglutide (Victoza). Her current antidiabetic regime consists of Detemir insulin, Aspart insulin prn, metformin, repaglinide, and canagliflozin with a current HBA1c of 7.7. Because of a positive history of CF in several grand children she had genetic testing that showed she is a heterozygous carrier of the Delta F5deletion mutation of the CFTR gene. Her ongoing diabetes care is without any further use of GLP-1 analogs. Our case series present two patients with class associated predilection for GLP-1 analog associated AP. Heterozygous carrier states for CF and HC may represent at risk clinical phenotypes for GLP-1 AP. Consideration should be given to genetic screening for these carrier states prior to commencing diabetic patients on GLP-1 analogs and possibly also DPP-4 inhibitors. Disclosure W.A. West: None. G.I. Uwaifo: None.

Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations

PurposeIsolation and identification of unknown impurities of recombinant insulin lispro (produced at IBA) formed during accelerated stability testing of pharmaceutical solutions. For comparative purposes also commercially available formulations of recombinant human insulin (Humulin S®; Lilly), recombinant insulin lispro (Humalog®; Lilly), recombinant insulin aspart (NovoRapid® Penfill®; Novo Nordisk), recombinant insulin detemir (Levemir®; Novo Nordisk) and recombinant insulin glargine (Lantus®; Sanofi-Aventis) were analyzed.MethodsThe impurities of insulin analogs were isolated by RP-HPLC and identified with peptide mass fingerprinting using MALDI-TOF/TOF mass spectrometry.ResultsThe identified derivatives were N-terminally truncated insulin analog impurities of decreased molecular mass of 119, 147 and 377 Da related to the original protein. The modifications resulting in a mass decrease were detected at the N-terminus of B chains of insulin lispro, insulin aspart, human insulin, insulin glargine, insulin detemir in all tested formulations. To our knowledge it is the first time that these impurities are reported.ConclusionsThe following derivatives formed by truncation of the B chain in insulin analogs were identified in pharmaceutical formulations: desPheB1-N-formyl-ValB2 derivative, desPheB1 derivative, pyroGluB4 derivative.

Evaluating the cost-effectiveness of insulin detemir versus neutral protamine Hagedorn insulin in patients with type 1 or type 2 diabetes in the UK using a short-term modeling approach.

BackgroundTo estimate the short-term cost-effectiveness of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) insulin based on the incidence of non-severe hypoglycemia and changes in body weight in subjects with type 1 diabetes (T1D) or type 2 diabetes (T2D) in the UK.MethodsA model was developed to evaluate cost-effectiveness based on non-severe hypoglycemia, body mass index, and pharmacy costs over 1 year. Published rates of non-severe hypoglycemia were employed in the T1D and T2D analyses, while reduced weight gain with IDet was modeled in the T2D analysis only. Effectiveness was calculated in terms of quality-adjusted life expectancy using published utility scores. Pharmacy costs were captured using published prices and defined daily doses. Costs were expressed in 2016 pounds sterling (GBP). Sensitivity analyses were performed (including probabilistic sensitivity analysis).ResultsIn T1D, IDet was associated with fewer non-severe hypoglycemic events than NPH insulin (126.7 versus 150.8 events per person-year), leading to an improvement of 0.099 quality-adjusted life years (QALYs). Costs with IDet were GBP 60 higher, yielding an incremental cost-effectiveness ratio (ICER) of GBP 610 per QALY gained. In T2D, mean non-severe hypoglycemic event rates and body weight were lower with IDet than NPH insulin, leading to a total incremental utility of 0.120, accompanied by an annual cost increase of GBP 171, yielding an ICER of GBP 1,422 per QALY gained for IDet versus NPH insulin.ConclusionShort-term health economic evaluation showed IDet to be a cost-effective alternative to NPH insulin in the UK due to lower rates of non-severe hypoglycemia (T1D and T2D) and reduced weight gain (T2D only).

Glycemic Control in Adult Type 1 Diabetes Patients with Insulin Glargine, Insulin Detemir, or Continuous Subcutaneous Insulin Infusion in Daily Practice.

This study aims to compare glycemic control of persons with type 1 diabetes using multiple daily injections (MDI) with insulin glargine versus insulin detemir or with continuous subcutaneous insulin infusion (CSII) in daily practice. All adult individuals with type 1 diabetes (n = 1053) were identified from the electronic patient database in North Karelia, Finland. The persons' individual data for insulin treatment, diabetic ketoacidosis (DKA), and hemoglobin A1c (HbA1c) measurements during the year 2014 were obtained from medical records. Persons using long-acting insulin analogs or CSII were included in the analyses (n = 1004). Altogether, 47.7% used glargine, 43.9% used detemir, and 8.4% used CSII. The mean HbA1c was lower in the CSII group (63 mmol/mol [7.9%]) compared with the glargine group (66 mmol/mol [8.2%]) or the detemir group (67 mmol/mol [8.3%]). The overall rate of DKA was 5.1% per year. The rate of DKA was higher in the detemir group compared with the glargine group (6.3% per year vs. 3.8% per year, respectively, P < 0.049). In logistic regression analyses, the higher rate of DKA with detemir use was explained by HbA1c. In daily practice, the glycemic control of type 1 diabetes patients with MDI was similar regardless of basal insulin, glargine, or detemir, whereas CSII allowed better glycemic control than MDI. The rate of DKA was higher with detemir than with glargine, but this is likely related to higher HbA1c rather than insulin regimen.

Pharmacodynamics and pharmacokinetics of insulin detemir and insulin glargine 300 U/mL in healthy dogs

Insulin glargine 300 U/mL and insulin detemir are synthetic long-acting insulin analogs associated with minimal day-to-day variability or episodes of hypoglycemia in people. Here, 8 healthy purpose-bred dogs each received 2.4 nmol/kg subcutaneous injections of insulin detemir (0.1 U/kg) and insulin glargine 300 U/mL (0.4 U/kg) on 2 different days, >1 wk apart, in random order. Blood glucose (BG) was measured every 5 min, and glucose was administered intravenously at a variable rate with the goal of maintaining BG within 10% of baseline BG (“isoglycemic clamp”). Endogenous and exogenous insulin were measured for up to 24 h after insulin injection. The effect of exogenous insulin was defined by glucose infusion rate or a decline in endogenous insulin. Isoglycemic clamps were generated in all 8 dogs after detemir but only in 4 dogs after glargine. Median time to onset of action was delayed with glargine compared to detemir (4.0 h [3.3–5.8 h] vs 0.6 h [0.6–1.2 h], P = 0.002). There was no difference in time to peak (median [range] = 6.3 h [5.0–21.3 h] vs 4.3 h [2.9–7.4 h], P = 0.15) or duration of action (16.3 h [6.1–20.1 h] vs 10.8 h [8.8–14.8 h], P = 0.21) between glargine and detemir, respectively. Glargine demonstrated a peakless time-action profile in 4/8 dogs. The total metabolic effect and peak action of detemir was significantly greater than glargine. Significant concentrations of glargine were detected in all but 1 dog following administration. Glargine might be better suited than detemir as a once-daily insulin formulation in some dogs based on its long duration of action and peakless time-action profile. Day-to-day variability in insulin action should be further assessed for both formulations.

Theoretical overview of clinical and pharmacological aspects of the use of etelcalcetide in diabetic patients undergoing hemodialysis.

Etelcalcetide is the first intravenous calcimimetic agent authorized for the treatment of secondary hyperparathyroidism (sHPT) in patients undergoing hemodialysis in Europe, the US, and Japan. The relationship between sHPT and diabetes resides on complex, bidirectional effects and largely unknown homeostatic mechanisms. Although 30% or more patients with end-stage renal disease are diabetics and about the same percentage of those patients suffer from sHPT associated with hemodialysis, no data on the specificities of the use of etelcalcetide in such patients are available yet. Regarding pharmacokinetic interactions, etelcalcetide may compete with oral hypoglycemics recommended for use in patients undergoing hemodialysis and insulins detemir and degludec, causing unexpected hypocalcemia or hypoglycemia. More importantly, hypocalcemia, a common side effect of etelcalcetide, may cause decompensation of preexisting cardiac insufficiency in diabetic patients or worsen dialysis-related hypotension and lead to hypotension-related cardiac events, such as myocardial ischemia. In diabetic patients, hypocalcemia may lead to dangerous ventricular arrhythmias, as both insulin-related hypoglycemia and hemodialysis prolong QT interval. Patients with diabetes, therefore, should be strictly monitored for hypocalcemia and associated effects. Due to an altered parathormone activity in this patient group, plasma calcium should be the preferred indicator of etelcalcetide effects. Until more clinical experience with etelcalcetide is available, the clinicians should be cautious when using this calcimimetic in patients with diabetes.

Characterisation of insulin analogues therapeutically available to patients.

The structure and function of clinical dosage insulin and its analogues were assessed. This included ‘native insulins’ (human recombinant, bovine, porcine), ‘fast-acting analogues’ (aspart, glulisine, lispro) and ‘slow-acting analogues’ (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

Reduction of glycemic variability with Degludec insulin in patients with unstable diabetes

SummaryIntroductionDegludec (IDeg) is an ultralong-acting insulin, with stable pharmacodynamic profile which leads to lower fluctuations in glucose levels. The effect of IDeg has not been specifically assessed in patients with unstable diabetes, defined as increased glycemic variability (GV).MethodsA prospective before-after pilot study was conducted, including patients managed at Hospital Universitario San Ignacio in Bogotá, Colombia. The impact of the switch from a Glargine or Detemir insulin to a basal insulin regimen with IDeg for 12 weeks on GV measured by continuous glucose monitoring, on A1c levels, and on the incidence of episodes of global and nocturnal hypoglycemia was assessed in a group of patients with (coefficient of variation >34%) or without increased basal GV using a Generalised Estimating Equation (GEE) analysis.Results60 patients with basal bolus therapy and history of hypoglycemia were included. 18 patients had High GV (HGV). In this group a significant reduction of 11.1% of CV (95% CI: 6.3, 15.9, p = 0.01) was found. GEE analysis confirmed a higher impact over time on patients with HGV (p < 0.001). The percentage of patients with at least 1 episode of hypoglycemia decreased from 66.6% to 22.2% (p = 0.02) and from 37.14% to 5.71% (p < 0.01) for global and nocturnal hypoglycemia, respectively. Changes were not significant in patients with low GV. A reduction of A1c was observed in both groups (p < 0.001).ConclusionsThe results suggest that treatment with IDeg reduces GV, A1c levels and the incidence of global and nocturnal hypoglycemia events in patients with HGV, but not in patients with low GV.

Genome-Wide Analyses Identify Filamin-A As a Novel Downstream Target for Insulin and IGF1 Action.

Insulin analogs were developed to improve diabetes therapy. However, certain modifications introduced into the insulin molecule were shown to enhance their affinity to the insulin-like growth factor-1 receptor (IGF1R). Most tumors, including endometrial cancers, express high levels of IGF1R. The present study was aimed at identifying the entire set of genes that are differentially activated by insulin glargine or detemir, in comparison to insulin and IGF1, in Type 1 and Type 2 endometrial cancer cell lines (ECC-1 and USPC-1, respectively). Global gene expression analyses demonstrated a ligand-dependent upregulated expression of filamin-A (FLNA), a gene that encodes an actin filament cross-linking protein, in both endometrial cancer cell types. Silencing experiments linked to migration assays confirmed the role of FLNA in cell growth and motility. Our data suggest that the activation of distinct sets of genes by glargine may lead to stimulation of specific pathways or, alternatively, may provide additive effects, different from those classically induced by insulin. Given that metastases are probably the main factor contributing to tumor invasiveness, the identification of FLNA as a downstream target for insulin-like hormones may be of translational relevance in oncology. Clinical studies in endometrial cancer may add further relevant information regarding the possible differential actions of insulin analogs with respect to native insulin.

Update on insulin treatment of dogs and cats with non-complicated diabetes mellitus

Diabetes mellitus is a common endocrine disease of dogs and cats. Treatment is mainly based on insulin administration and dietary modifications. The aim of this review is to provide updated information on insulin treatment of dogs and cats with non-complicated diabetes mellitus. During the last years, there has been significant progress in the management of this disease, thanks to the use of long-acting insulin preparations that do not cause pronounced fluctuations of blood glucose concentrations (insulin glargin and detemir) and because of the widespread use of home glucose monitoring by the owners of diabetic pets. Home glucose monitoring is based on capillary blood sampling from the ear pinnae or the foot pad and measurement of blood glucose concentration with a portable blood glucose meter. This can be done periodically (e.g. every week) to replace the traditional in-clinic blood glucose curve; in this case, blood glucose concentration is measured just before the morning insulin administration and then every 1-2 hours until the next dose (usually for 12 hours). Furthermore, especially for the cat, home glucose monitoring can be performed 3-5 times per day, on a daily basis, in order to safely adjust insulin dose and achieve tight control of hyperglycemia (i.e. blood glucose concentration between 50 and 200 mg dl-1 throughout the day). The combination of dietary management, of insulin glargine or detemir administration and of the tight control of hyperglycemia has substantially increased the proportion of cats that enter into temporal or permanent diabetic remission and can be further managed without insulin. Another important achievement is the use of continuous glucose monitoring systems to monitor interstitial fluid glucose concentrations. These devices can be used in the clinic and at home and they can measure glucose concentration every 5 minutes for up to 72 consecutive hours, thus facilitating optimal adjustment of insulin treatment.

Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin.

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla‐100) or insulin detemir (DET) with ≥1 A1C measurement during 12‐month baseline and 18‐month follow‐up periods were included. Patients with a refill gap of >90 days were considered non‐persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow‐up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non‐persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Quality-of-life and treatment satisfaction in actual clinical practice of patients with Type 1 diabetes mellitus (T1DM) and hypoglycemia treated with insulin degludec

Objective: The frequency of hypoglycemia in patients with T1DM is high and results in a poorer quality-of-life and low treatment satisfaction. The aim of this study is to demonstrate the effect of changing the basal insulin (glargine or detemir) to insulin degludec.Methods: An observational analytical study was conducted on a cohort of 110 patients with T1DM. The patients were administered three questionnaires to assess treatment satisfaction (DTSQ-s), fear of hypoglycemia (HFS-II) and quality-of-life (EQ-5D), before the change and at 6 months. A statistical analysis was performed for repeated measures.Results: The 110 patients with T1DM had a mean diabetes duration of 19.1 (11.6) years, 53.6% were men, the mean age was 43.4 (15.4) years, and the mean BMI was 25.2 (4.2) kg/m2. After 6 months, there was a significant reduction in baseline fasting plasma glucose (from 159.1 [68.6] to 132.9 [56.6] mg/dL; p < .001) and HbA1c levels (from 7.82% [1.2] to 7.6% [1.2]; p = .002). A reduction in the number of severe hypoglycemic episodes (0.17 [0.5] vs 0.05 [0.2]; p = .03) was observed. At 6 months, an improvement in the DTSQ-s (from 24.3 [5.5] to 27.3 [5.4]; p < .001) was observed. There was a decrease in the mean number of perceived hypoglycemia (from 2.9 [1.4] to 2.3 [1.4]; p = .003) and hyperglycemia (from 3.5 [1.3] to 2.7 [1.4]; p < .001). There was also a decrease in the mean HFS-II score (from 24.1 [14.0] to 20.0 [13.0]; p < .001). There were no significant differences in the EQ-5D index (from 0.91 [0.14] to 0.89 [0.16]; p = .13). However, there was significant improvement in the EQ-5D as measured by VAS (from 70.5 [16.5] to 73.6 [14.4]; p = .04).Conclusions: The change to insulin degludec in patients with T1DM improved their metabolic control, increased their satisfaction with the insulin therapy, and offered them improved quality-of-life.

Effect of short-term intensive insulin therapy on the incretin response in early type 2 diabetes

AimsShort-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes. MethodsIn this study, 63 patients (age 59±8.3 years, baseline A1c 6.8±0.7%, diabetes duration 3.0±2.1 years) underwent 4 weeks of IIT (basal insulin detemir and pre-meal insulin aspart). GLP-1, GIP and glucagon responses were assessed by the area-under-the-curve (AUC) of these hormones on oral glucose tolerance tests at baseline and 1-day after the completion of therapy. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), with insulin resistance measured by Homeostasis Model Assessment (HOMA-IR). ResultsAs expected, comparing the post-therapy oral glucose tolerance test to that at baseline, IIT increased ISSI-2 (P=0.02), decreased HOMA-IR (P<0.001), and reduced AUCglucagon (P<0.001). Of note, however, IIT had no significant impact on AUCGLP-1 (P=0.24) and reduced AUCGIP (P=0.02). ConclusionDespite improving beta-cell function, insulin resistance and glucagonemia, short-term IIT does not change GLP-1 secretion and decreases the GIP response to an oral glucose challenge in early type 2 diabetes. Thus, the beneficial impact of this therapy on glucose homeostasis is not attributable to its effects on incretin secretion.

COST-EFFECTIVENESS ANALYSIS OF INSULIN REGIMEN ON TYPE 2 DIABETES MELLITUS OUTPATIENT IN DENPASAR MUNICIPALITY

Objective: Insulin is one of the antidiabetic agents that available for the treatment of type 2 diabetes mellitus (T2DM) patients. Insulin has several types of formulation, with its cost and effectiveness. The aim of this study was to compare the cost-effectiveness of insulin regimen in the therapy management of T2DM outpatient.Methods: Cost-effectiveness analysis has been done by calculating the average cost-effectiveness ratio (ACER) and incremental cost-effectiveness ratio (ICER) of each insulin regimens. Effectiveness was measured by improvement of fasting blood glucose, postprandial blood glucose, and HbA1c value. The total cost of insulin regimen was calculated from direct medical cost, direct nonmedical cost, and indirect nonmedical cost.Results: Overall, 42 patients meet the inclusion criteria were included this study. There were four insulin regimens compared, namely, insulin detemir,premixed insulin aspart, insulin aspart, and a combination of insulin aspart + insulin glargine. The combination of insulin aspart + insulin glargine provides pre-eminent therapy effectiveness (58.82%), whereas insulin detemir regimen has the lowest total cost (102.62 USD). Calculation of ACER showed that insulin aspart has the lowest ACER value, in an amount of 1.91 USD per percentage of effectiveness. Based on ICER value, insulin aspart was the better choice compared to the combination of insulin aspart + insulin glargine (0.18 USD vs. 0.82 USD).Conclusion: The variation of therapeutic effectiveness and total cost was observed in the management of T2DM outpatient. Based on ACER and ICER value, insulin aspart was the most cost-effective insulin compared to another insulin regimen on the study.

COST-EFFECTIVENESS ANALYSIS OF INSULIN REGIMEN ON TYPE 2 DIABETES MELLITUS OUTPATIENT IN DENPASAR MUNICIPALITY

Objective: Insulin is one of the antidiabetic agents that available for the treatment of type 2 diabetes mellitus (T2DM) patients. Insulin has several types of formulation, with its cost and effectiveness. The aim of this study was to compare the cost-effectiveness of insulin regimen in the therapy management of T2DM outpatient.Methods: Cost-effectiveness analysis has been done by calculating the average cost-effectiveness ratio (ACER) and incremental cost-effectiveness ratio (ICER) of each insulin regimens. Effectiveness was measured by improvement of fasting blood glucose, postprandial blood glucose, and HbA1c value. The total cost of insulin regimen was calculated from direct medical cost, direct nonmedical cost, and indirect nonmedical cost.Results: Overall, 42 patients meet the inclusion criteria were included this study. There were four insulin regimens compared, namely, insulin detemir,premixed insulin aspart, insulin aspart, and a combination of insulin aspart + insulin glargine. The combination of insulin aspart + insulin glargine provides pre-eminent therapy effectiveness (58.82%), whereas insulin detemir regimen has the lowest total cost (102.62 USD). Calculation of ACER showed that insulin aspart has the lowest ACER value, in an amount of 1.91 USD per percentage of effectiveness. Based on ICER value, insulin aspart was the better choice compared to the combination of insulin aspart + insulin glargine (0.18 USD vs. 0.82 USD).Conclusion: The variation of therapeutic effectiveness and total cost was observed in the management of T2DM outpatient. Based on ACER and ICER value, insulin aspart was the most cost-effective insulin compared to another insulin regimen on the study.

Efficacy and Safety of Insulin Glargine 300 U/mL versus 100 U/mL in Diabetes Mellitus: A Comprehensive Review of the Literature.

To achieve good metabolic control in diabetes and maintain it in the long term, a combination of changes in lifestyle and pharmacological treatment is necessary. The need for insulin depends upon the balance between insulin secretion and insulin resistance. Insulin is considered the most effective glucose-lowering therapy available and is required by people with type 1 diabetes mellitus to control their blood glucose levels; yet, many people with type 2 diabetes mellitus will also eventually require insulin therapy, due to the progressive nature of the disease. A variety of long-acting insulins is currently used for basal insulin therapy (such as insulin glargine, degludec, and detemir), each having sufficient pharmacodynamic and pharmacokinetic profiles to afford lower intrapatient variability and an extended duration of action. The new glargine-300 formulation was developed to have a flatter and more extended time-action profile than the original glargine-100, and these characteristics may translate into more stable and sustained glycemic control over a 24 h dosing interval. The objective of this comprehensive review was to summarize the available evidence on the clinical efficacy and safety of glargine-300 versus glargine-100 from the EDITION clinical trial program, in patients with type 1 and type 2 diabetes mellitus.

Reduced Efficacy of Insulin Detemir in Controlling Hyperglycemia during Pregnancy: An Interesting Case Report.

Reduced Efficacy of Insulin Detemir in Controlling Hyperglycemia during Pregnancy: An Interesting Case Report.

The influence of dopamine-beta-hydroxylase and catechol O-methyltransferase gene polymorphism on the efficacy of insulin detemir therapy in patients with type 2 diabetes mellitus

BackgroundType II diabetes is an important health problem with a complex connection to obesity, leading to a broad range of cardiovascular complications. Insulin therapy often results in weight gain and does not always ensure adequate glycemic control. However, previous studies reported that insulin detemir is an efficient long-acting insulin with a weight sparing effect. The aim of this study was to determine the association of catechol O-methyltransferase (COMT) Val108/158Met and dopamine-beta-hydroxylase (DBH) 1021C/T polymorphisms with the effectiveness of insulin detemir in achieving glucose control and body weight control. Participants and methods: This 52-week observational study included 185 patients with inadequate glycemic control treated with premix insulin analogues, which were replaced with insulin aspart and insulin detemir, and 156 healthy controls. After DNA isolation from blood samples, genotyping of DBH-1021C/T polymorphism (rs1611115) and COMT Val108/158Met polymorphism (rs4680) was performed.ResultsOur results confirmed that insulin detemir did not lead to weight gain. The most significant finding was that A carriers (the combined AG and AA genotype) of the COMT Val108/158Met achieved significantly better hemoglobin A1c (HbA1c) values compared to patients carrying GG genotype. No association between DBH-1021C/T genotypes and weight and/or glucose control was detected in diabetes patients or in healthy control subjects.ConclusionsThis study showed that the presence of one or two A allele of the COMT Val108/158Met was associated with improved glycemic response, and with a better response to insulin detemir therapy in patients with type II diabetes, separating them as best candidates for detemir therapy.

Challenges and unmet needs in basal insulin therapy: lessons from the Asian experience.

Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia.

Impact of Insulin Detemir Administration Time on Hypoglycemia Rates in Hospitalized Patients.

To determine if insulin detemir administration time affects the frequency of hypoglycemia (blood glucose level <70mg/dl) in hospitalized patients. Retrospective cohort study. A total of 357 adults (aged 18-89yrs) who received insulin detemir for at least 48hours while hospitalized between January 1, 2014, and December 31, 2015, were included. Patients were categorized into one of three groups according to insulin detemir administration time: detemir given once/day between 7 a.m. and 10 a.m. (AM group [71 patients]), detemir given once/day between 6 p.m. and 10 p.m. (PM group [158 patients]), and detemir given twice/day (BID group [128 patients]). Community hospital. The primary outcome was the percentage of patient days with any occurrence of hypoglycemia. The key secondary outcomes included the percentages of patients who experienced any hypoglycemic event, severe hypoglycemia, hypoglycemia requiring treatment, and refractory hypoglycemia; time of hypoglycemia; and percentage of patients experiencing one or more episodes of hyperglycemia. The AM group had a lower proportion of days with hypoglycemia compared with the PM group (7.9% vs 11.9%, p=0.008). There was a nonsignificant trend toward a lower proportion of days with hypoglycemia in the BID group compared with the PM group (9.1% vs 11.9%, p=0.0302). No significant differences in percentage of patient days with hyperglycemia and rates of severe hypoglycemia, hypoglycemia requiring treatment, or refractory hypoglycemia were noted among the three groups. Administration of detemir in the morning may reduce the occurrence of hypoglycemia in hospitalized patients. Institutions that include detemir on their formularies may consider evaluating the incidence of hypoglycemia and modifying administration schedules as part of their medication safety program.