Detemir Research Articles

Real-world persistence, adherence, health care resource utilization, and costs in people with type 2 diabetes switching from a first-generation basal insulin to a second-generation (insulin glargine 300 U/mL) vs an alternative first-generation basal insulin.

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers' bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

Interaction of esomeprazole with insulin detemir and human albumin: A potential cause of hypoglycemia

Insulin detemir (IDt) is long-acting insulin whose protraction mechanism is based on a covalently attached fatty acid to an insulin molecule. Utilizing the high affinity of fatty acids towards human serum albumin (HA), the modified detemir molecule binds with good affinity to HA, which functions as a reservoir that leads to a slow and prolonged release of insulin. However, questions were raised over potential interactions between other drugs and IDt through competitive binding on the binding site(s) of HA. In a previous study, concomitant use of esomeprazole (Esom) and erythromycin resulted in severe hypoglycemia, and thus: the drugs including Esom were suggested as enhancers of IDt action through displacing it from its binding site on HA. To further study this possibility, studies utilizing different techniques including, semipermeable membrane dialysis, capillary electrophoresis, UV,NMR spectroscopy, and molecular docking were carried out. Results from various techniques supported the simultaneous binding of Esom along with IDt to HA (i.e., binding in two different sites without signs of competition between the two). Moreover, capillary electrophoresis suggested an increase in the binding affinity of Esom to HA in the presence of IDt (1.9 × 103 Vs 2.7 × 104M−1). Perhaps most interesting was the observation that Esom could bind directly to IDt which was evidenced by all the employed techniques. Direct binding of Esom to IDt, might explain the enhancement in insulin action associated with the concomitant use of Esom. Therefore, Esom might represent a leading insulin-sensitizing compound that might lead to more effective insulin enhancing and less unwanted effects.

Abstract 6: Maternal efficacy, safety, and pregnancy outcomes with degludec versus detemir in the treatment of pregnant women with type 1 diabetes: An international, multicentre, randomised trial

Background and Aims:To compare the efficacy and safety of insulin degludec (degludec) versus insulin detemir (detemir) in pregnant women with type 1 diabetes (T1D).Materials and Methods:EXPECT was an open-label, randomised trial of women aged ≥18 years with T1D and previously treated with insulin, who were at 8-13 weeks’ gestation or planned to become pregnant within 52 weeks. Women were randomised to degludec once daily or detemir 1- 2 times daily, both with insulin aspart 2-4 times daily. The primary analysis aimed to demonstrate the non-inferiority (margin of 0.4%) of degludec to detemir with respect to the last planned glycated haemoglobin (HbA1c) measurement prior to delivery (>16 weeks’ gestation) using ANCOVA. Secondary endpoints were maternal efficacy, safety, and pregnancy outcomes.Results:In total, 225 women (degludec: 111; detemir: 114) were randomised including 144 who were, and 81 who planned to become pregnant. Mean (±SD) HbA1c at treatment baseline was 6.8% (±0.7%) and 6.7% (±0.8%) with degludec and detemir, respectively. Over the trial, 188 women (degludec: 92; detemir: 96) with singleton pregnancies were included and there were 171 live-born infants (degludec: 86; detemir: 85), with no perinatal deaths (between ≥20 week's gestation and and <1 week after delivery). Estimated mean HbA1c prior to delivery was 6.23% with degludec and 6.34% with detemir (estimated treatment difference: −0.11% [−0.31; 0.08]95% CI, confirming non-inferiority). See Table for supportive maternal safety and pregnancy outcomes.TableSupportive maternal safely and pregnancy outcomes in women with type 1 diabetes randomised to degijdec or detemirDegludecDetemir n/N%EventsRalen/N%EventsRaleMaternal safer/ outcomosOverall hypoglycaemia89.’9197.8543111.84591/94968598213,401Nocturnal hypoglycaemia*71/9178.0712155369/9473.47591700Adjudicated severe hypoglycaemia‡6/916.68-3:943.24-Adverse events78/9185.742993676/9480.9328735Pre-edampsia12/8814.0--7/858.2--Pregnancy outcomesfctusevinfants with major abnormalities§8/928.7--8:968.3--Pre-teim delivery (<37 vreeks’ gestation)¶29/8633.7--19/85224--Infants born large for gestabonal age55/86840--4A8550.6--Infants with neonatal hypoglycaemia††20/8623.3--19/8522.4--Maternal safety outcomos were assessed over the pregnancy period and based on all randomised women who weie pregnant during the trial and received 21 dose of trial product. Additionally, tor pre-eciampsa. only women who delvered an infant at 220 weeks’ gestation were considered. Pregnancy outcomes were based on all randomised women who delivered an infant at ≤20 weeks’ gestation, except tor major abnormalities, where all randomised women who were pregnant during the trial were considered The analyses of maternal safety and pregnancy enidpoints were pre-specified to provide a descriptive summary only†Events occurhng between 00:01 and 05:59 (both inclusive): ‡events requiring third-party assistance; §UROCAT classified; ¶affer 20 weeks’ gestation: ††defined as blood glucose t .7 mmol/l (≤31 mg/dL) and assessed over the first 24 hours after birth.%. percentage of women with ≥ event: degludec. insulin degludec. detemir. insulin detemir; EUROCAT, European Concerted Action on Congenital Abnormalities and Twins; n, number of women with ≥1 event; N, total number of women In treatment group and analysis set: rate, rate of events per 100 years of exposure.Conclusion: In pregnant women with T1D, degludec was non-inferior to detemir with respect to HbA1c prior to delivery. Hypoglycaemia rates and pregnancy outcomes were comparable between insulins.

A Single Center, Open-Labeled Trial to Investigate the Pharmacokinetics of Insulin Detemir in Healthy Taiwanese Subjects

Backgrounds: Insulin detemir (NN304) is a long-acting insulin analogue reported to provide more predictable blood glucose level throughout the day, leading to a lower within-subject variability compared to NPH insulin. Pharmacokinetic profiles of insulin detemir had not been investigated in Taiwanese. This study was to determine whether there is a difference between Taiwanese subjects in pharmacokinetic profile of insulin detemir compared to Caucasian subjects. Methods: Pharmacokinetic profile of insulin detemir was measured in twenty male Taiwanese (NN304-3023). Eligible subjects were given insulin detemir as a single dose subcutaneous injection at 0.5 U/kg body weight in the mid-thigh using NovoPen® 3 device. 32-hour serum insulin detemir concentrations were measured. Hypoglycemia and other adverse events were recorded. The results were compared to data obtained from a previous trial in Caucasian subjects (NN304-1451). Results: There was no significant difference between Taiwanese (NN304-3023) and Caucasian (NN304-1451) in the primary endpoint, AUC(0–∞) , and the secondary endpoints, AUC(0–24h), and t1/2. However, the secondary endpoints, Cmax was 40% higher, tmax was shorter (270.0 vs 420.0 min) and AUC(0–5h) was 2-fold more in Taiwanese. When only male subjects were included in the comparator trial (NN304-1451), the t1/2 was significantly shorter in Taiwanese (348 min vs 404 min). There was no significant difference in the mean blood glucose concentrations between Taiwanese and Caucasian subjects. A single episode of hypoglycemia (53 mg/dL) was reported in a 24-year-old male approximately 2.5 hours after the administration of insulin detemir. He was able to treat himself for the episode. Conclusion: In this pharmacokinetic evaluation of a single dose administration of insulin detemir in Taiwanese male subjects, the AUC(0–∞) , and AUC(0–24h) were not different from that of Caucasians in the comparator trial. However, insulin detemir appeared to be more rapidly absorbed in Taiwanese males. Further studies are warranted to elucidate its pharmacodynamic response and mechanisms. Finally, there was no clinically relevant safety concern raised in this study (Funded by research grant from Novo Nordisk, Taiwan, first registration (22/12/2011) ClinicalTrials.gov number, NCT01497587).

Development and Validation of a Stability-indicating HPLC Method for Determination of Insulin Detemir and Preservatives in their Injection Products

Insulin detemir (ID) is a long-acting form of insulin that is characterized by the covalent attachment of a lipophilic tail of myristate, and commercially available as Levemir®. No satisfactory simple isocratic stability-indicating HPLC method has been reported for its quality control. A novel simple and isocratic reversed-phase HPLC method was developed and validated for the simultaneous determination of ID along with its dosage form additives in the available commercial preparations. The method employed C4 column (5μm, 250 × 4.6 mm), a mobile phase consisting of 50 mM phosphate buffer pH 2.7, acetonitrile, triethylamine (62:37:1) and 0.02 g/ml sodium sulfate, that was delivered isocraticaly at a flow rate of 1.5 ml/min, and detection performed at 214nm. The method was properly validated and was shown linear over the range 80–120% of the assay concentration for ID, phenol, and m-cresol. The method was also selective, specific, precise, and accurate. Furthermore, the validated method was applied to separate the major degradation products in those preparations. Forced degradation studies in different pH values, which are the first to be reported for ID, showed that the degradation products were baseline separated from ID itself and/or other formulation additives. Thus, the method has been demonstrated to be a stability-indicating assay.

Comparison of Efficacy of Detemir and Degludec Insulin in the Management of Children and Adolescents with Type 1 Diabetes

Aims and Objectives: Despite the advantages offered by current basal analogs, the management of type 1 diabetes (T1D) in children and adolescents is a great challenge till now. Insulin degludec (IDeg) is alternative basal insulin to be used in persons not responding to other basal insulins. The aim of the study was to compare the efficacy of IDeg (once daily) and insulin detemir (IDet) in children and adolescents with T1D in Bangladesh. Materials and Methods: In this retrospective analysis, we included T1D patients who were treated with IDet or IDeg in CDiC Diabetes Center, BIRDEM Hospital from January to June 2018. Thirty patients with IDeg were compared with 30 patients who were taking IDet; patients were randomly selected from the data set. Insulin dose requirement, weight, body mass index, fasting plasma glucose (FPG), and HbA1c were compared at the base level and at three and six months after treatment. Results: While comparing between two groups, the median FPG was high, 15.0 (13.6–18.3) vs. 14.4 (10.5–16.9), in both groups at the base level. Over the six months, FPG was gradually reduced in both groups but significantly reduced in IDeg patients (P = 0.03), although median HbA1c was higher, 9.9 (8.4–12.0), in IDeg patients than in IDet patients, 9.3 (8.1–10.4), at the base level but reduced significantly in IDeg patients, 8.4 (7.6–9.0), compared with IDet patients, 9.0 (8.1–9.7), after six months (P = 0.042). Though mild hypoglycemia was documented, there was no incidence of severe hypoglycemia in IDet or IDeg groups. Conclusion: In conclusion, in our study population, the IDeg group had more improvement in glycemic control, reducing FPG, than the IDet group. Moreover, there was more reduction of basal insulin dose in IDeg than in IDet after six months of starting the therapy.

Blood Glucose Management in Gestational Diabetes

The prevalence of gestational diabetes mellitus (GDM) has been increasing globally and in India too, because of urbanization and the increasing occurrence of obesity. The management of GDM poses a clinical challenge, and this article focuses on its diagnosis and treatment. In India, screening of all pregnant women is recommended at the first antenatal visit and then repeat screening at 24–28 weeks of gestation if the initial screen is normal. Early intervention with counseling, glucose monitoring, diet, and exercise to achieve good glucose control could reduce both the maternal and fetal complications associated with hyperglycemia in pregnancy. The majority of cases of GDM may be managed by lifestyle modifications alone. Metformin may be prescribed as an alternative to insulin as per certain guidelines, though insulin remains the cornerstone of pharmacotherapy. Long-acting insulin detemir and short-acting insulin analogs such as insulin lispro or aspart are safe in pregnancy and help with control of blood glucose. Good glycemic control, achieved by lifestyle measures, monitoring, and medications when needed, may help achieve the goal of a successful pregnancy outcome.

Meta-analysis of insulin detemir treatment of pregnancy with diabetes

Meta-analysis of insulin detemir treatment of pregnancy with diabetes

ANALYSIS OF THE COST EFFECTIVENESS OF THERAPY IN HYPERTENSION AND TYPE 2 DIABETES MELLITUS PATIENTS IN OUTSTANDING INSTALLATION RSUD TOTO KABILA

Hypertension and diabetes mellitus are degenerative diseases where various therapies are certainly used so that the effectiveness of each drug and the costs incurred need to be considered. The more treatments used, the more costs will be incurred. Therefore, a pharmacoeconomic analysis needs to be carried out to assist decision making in performing therapy. This research was a non-experimental research with descriptive analysis design. Data collection was retrospective by tracing previous documents sourced from medical records of patients with hypertension and Type 2 Diabetes Mellitus (DM) at the Outpatient Installation of Toto Kabila Regional General Hospital for the period of October to December 2020. Samples were taken by purposive sampling technique and then the data obtained were analyzed by calculating the direct medical costs and drug effectiveness. Data analysis from this study used Cost Effectiveness Analysis (CEA) and was continued in the form of ratio, namely Average Cost Effectiveness Ratio (ACER) or Incremental Cost Effectiveness ratio (ICER). The results showed that in hypertension, drug therapy used were Amlodipine (47.8%) and Candesartan (52.2%), while in Type 2 DM therapy were the combination of Metformin and Glimepiride (68.9%) and the combination of Insulin-Aspart and Insulin Detemir (31.1%). The direct medical cost of hypertension therapy with Amlodipine was Rp. 184.921, and Candesartan was Rp. 158.159. As for the Type 2 DM therapy, the cost of Metformin-Glimepiride combination was Rp. 168.253,226 and the combination of Insulin-Aspart and Insulin-Detemir of Rp. 1.077.259. The results of the cost effectiveness calculation show that Candesartan is more cost-effective than Amlodipine, while the combination of Metformin-Glimepirid is more cost-effective than the combination of Insulin-Aspart and Insulin-Detemir.

Clinical outcomes in high-hypoglycaemia-risk patients with type 2 diabetes switching to insulin glargine 300U/mL versus a first-generation basal insulin analogue in the United States : Results from the DELIVER High Risk real-world study.

AimsTo compare 12‐month clinical effectiveness of insulin glargine 300 units/mL (Gla‐300) versus first‐generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla‐100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla‐300 or Gla‐100/IDet) in a real‐world setting.MethodsDELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla‐300 (Gla‐300 switchers) and were propensity score‐matched (1:1) to patients who switched to Gla‐100 or IDet (Gla‐100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all‐hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact).ResultsHbA1c reductions were similar following switching to Gla‐300 or Gla‐100/IDet (−0.51% vs. −0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all‐hypoglycaemia incidence and event rates. However, the Gla‐300 switcher cohort had a significantly lower risk of inpatient/ED‐associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60–0.89; p = .002) and experienced significantly fewer inpatient/ED‐associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001).ConclusionIn patients with T2D at high risk of hypoglycaemia, switching to Gla‐300 or Gla‐100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla‐300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching.

Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa.

Intranasal drug delivery is a promising approach for the delivery of drugs to the CNS, but too heterogenous, unprecise delivery methods without standardization decrease the quality of many studies in rodents. Thus, the lack of a precise and region-specific application technique for mice is a major drawback. In this study, a previously developed catheter-based refined technique was validated against the conventional pipette-based method and used to specifically reach the olfactory or the respiratory nasal regions. This study successfully demonstrated region-specific administration at the olfactory mucosa resulting in over 20% of the administered fluorescein dose in the olfactory bulbs, and no peripheral bioactivity of insulin detemir and Fc-dependent uptake of two murine IgG1 (11C7 and P3X) along the olfactory pathway to cortex and hippocampus. An scFv of 11C7 showed hardly any uptake to the CNS. Elimination was dependent on the presence of the IgG’s antigen. In summary, it was successfully demonstrated that region-specific intranasal administration via the olfactory region resulted in improved brain targeting and reduced peripheral targeting in mice. The data are discussed with regard to their clinical potential.

Switching the basal insulin to insulin glargine 300 U/ml in people with type 2 diabetes under basal insulin supported oral therapy: Observational trial on effectiveness and safety.

This study evaluated the effectiveness and safety of switching the basal insulin (BI) in a BI-supported oral therapy (BOT) to insulin glargine 300 U/ml (Gla-300) in adults with inadequately controlled type 2 diabetes (T2D). This was a non-interventional, multicentre, prospective 12-month study, conducted in Germany, Austria and Switzerland. The study documented people with T2D with glycated haemoglobin (HbA1c) between 7.5% and 10.0%, currently treated by a non-Gla-300 BOT regimen, after the physician had decided to switch the BI to Gla-300. Primary endpoint was the proportion of patients achieving the fasting plasma glucose (FPG; ≤110 mg/dl) target. In total, 1194 participants comprised the full analysis set, of which 793 completed documentation of 12 months Gla-300 treatment (FAS-M12). The main previous BI was insulin glargine 100 U/ml (Gla-100; 47.2%). Twelve months after switching to Gla-300, 27.0% of FAS-M12 participants achieved the FPG target and 44.8% their individualized HbA1c target. The greatest FPG target achievements were seen in previous Gla-100 (29.3%), and greatest HbA1c target achievements in previous insulin detemir users (57.7%). The mean FPG decreased by -36.3 ± 51.2mg/dl to 135.5 ± 36.9mg/dl and mean HbA1c by -0.79 ± 1.01% to 7.45 ± 0.94%. Symptomatic and nocturnal hypoglycaemia incidence significantly decreased over 12 months of Gla-300 treatment. Body weight remained unchanged. Switching the BI to Gla-300 in a BOT regimen improved metabolic control and treatment satisfaction in a substantial proportion of patients with T2D and inadequate target achievement within 12 months in clinical practice with a decreased risk of symptomatic and nocturnal hypoglycaemia and without weight gain.

Clinical Efficacy and Safety of Insulin Detemir Combined with Repaglinide in the Treatment of Type 2 Diabetes

Clinical Efficacy and Safety of Insulin Detemir Combined with Repaglinide in the Treatment of Type 2 Diabetes

Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study.

OBJECTIVETo compare the risk of severe adverse pregnancy complications in women with preexisting diabetes.RESEARCH DESIGN AND METHODSMultinational, 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.RESULTSOf 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI −0.01, 0.04]; adjusted risk difference −0.003 [95% CI −0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064, 0.000]) and after (−0.036 [95% CI –0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference −0.181 [95% CI −0.300, −0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; −0.139 [95% CI −0.232, −0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference −0.030 [95% CI −0.058, −0.002]), preeclampsia (6.4% vs. 10.0%; −0.036 [95% CI −0.064, −0.007]), and stillbirth (0.4% vs. 1.8%; −0.013 [95% CI −0.024, −0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment.CONCLUSIONSInsulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

Optimization of pig models for translation of subcutaneous pharmacokinetics of therapeutic proteins: Liraglutide, insulin aspart and insulin detemir

Prediction of human pharmacokinetics (PK) from data obtained in animal studies is essential in drug development. Here, we present a thorough examination of how to achieve good pharmacokinetic data from the pig model for translational purposes by using single-species allometric scaling for selected therapeutic proteins: liraglutide, insulin aspart and insulin detemir. The predictions were based on non-compartmental analysis of intravenous and subcutaneous PK data obtained from two injection regions (neck, thigh) in two pig breeds, domestic pig and Göttingen Minipig, that were compared with PK parameters reported in humans. The effects of pig breed, injection site and injection depth (insulin aspart only) on the PK of these proteins were also assessed. Results show that the prediction error for human PK was within two-fold for most PK parameters in both pig breeds. Furthermore, pig breed significantly influenced the plasma half-life and mean absorption time (MAT), both being longer in Göttingen Minipigs compared to domestic pigs (P <0.01). In both breeds, thigh vs neck dosing was associated with a higher dose-normalized maximum plasma concentration and area under the curve as well as shorter MAT and plasma half-life (P <0.01). Finally, more superficial injections resulted in faster absorption, higher Cmax/dose and bioavailability of insulin aspart (P <0.05, 3.0 vs 5.0 mm injection depth). In conclusion, pig breed and injection region affected the PK of liraglutide, insulin aspart and insulin detemir and reliable predictions of human PK were demonstrated when applying single-species allometric scaling with the pig as a pre-clinical animal model.

Post Hoc Analysis Evaluating the Impact of Antihyperglycemic Background Therapies on Attainment of A1C Targets Without Hypoglycemia in the ACHIEVE Control Pragmatic, Real-Life Study.

BackgroundACHIEVE Control, a prospective, open-label, randomized, pragmatic, real-life study in insulin-naive people with type 2 diabetes (A1C 8.0–11.0%), demonstrated superiority of insulin glargine 300 units/mL (Gla-300) versus first-generation standard-of-care basal insulin (SOC-BI; glargine 100 units/mL or insulin detemir) in achieving individualized A1C targets without documented symptomatic (glucose ≤3.9 mmol/L [≤70 mg/dL] or <3.0 mmol/L [<54 mg/dL]) or severe hypoglycemia (American Diabetes Association level 3) at 6 months. Noninsulin antihyperglycemic background therapies are commonly used; however, sulfonylureas may increase hypoglycemia risk. This post hoc analysis assessed outcomes according to background therapy.MethodsSubgroup analyses were performed per concomitant use/nonuse of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, or sodium–glucose cotransporter 2 (SGLT2) inhibitors. End points (6 and 12 months) included A1C target attainment without documented symptomatic or severe hypoglycemia, A1C target attainment, and absence of documented symptomatic or severe hypoglycemia.ResultsOdds ratios (ORs) at 12 months mostly favored Gla-300 versus SOC-BI across subgroups except in analysis of SGLT2 inhibitors, in which ORs were similar. Among sulfonylurea users, ORs at 12 months strongly favored Gla-300 versus SOC-BI for all end points, particularly A1C target achievement without documented symptomatic hypoglycemia (glucose ≤3.9 mmol/L [≤70 mg/dL]; OR 1.25, 95% CI 1.02–1.53) or severe hypoglycemia and achievement of no documented symptomatic hypoglycemia (glucose <3.0 mmol/L [<54 mg/dL]; OR 1.25, 95% CI 1.02–1.52) or severe hypoglycemia.ConclusionThe results suggest that, in insulin-naive people with type 2 diabetes, Gla-300 is effective with a risk of hypoglycemia that is lower than or similar to that of SOC-BI regardless of background medication. Individuals receiving concomitant sulfonylureas were more likely to remain without symptomatic or severe hypoglycemia with Gla-300.

Adverse events with insulin detemir vs other basal insulins

Adverse events with insulin detemir vs other basal insulins

Choice of basal insulin therapy is associated with weight and height development in type 1 diabetes: A multicenter analysis from the German/Austrian DPV registry in 10 338 children and adolescents.

Available basal insulin regimes differ in pharmacokinetic profiles, which may be related to subsequent changes in anthropometry in patients with type 1 diabetes. This analysis elucidates the standardized height and body mass index development (height and BMI standard deviation score [height-SDS and BMI-SDS]) in pediatric type 1 diabetes patients depending on the choice of basal insulin. Longitudinal data of 10 338 German/Austrian patients from the Diabetes Prospective Follow-up (DPV, Diabetes Patienten Verlaufsdokumentation) database were analyzed. Patients aged 5.0 to 16.9 years were treated exclusively with neutral protamine Hagedorn (NPH), insulin detemir (IDet), insulin glargine (IGla), or continuous subcutaneous insulin infusion (CSII) for at least 3 years. Population-based German reference data were used to calculate height-SDS and BMI-SDS. Multiple linear regression was conducted. BMI-SDS increased significantly in all regimes (NPH P= .0365; IDet P= .0003; IGla P< .0001; and CSII P< .0001). Direct comparison of the therapies revealed a favorable association only for NPH vs IGla. A rise in BMI-SDS was observed for all insulins in females, but only for IGla in males. BMI-SDS increment was not observed before 8 years of age. Initially and at the end of the observation period, mean height was above the 50th percentile of the reference population. Across the cohort, height-SDS declined during the observation period, except for CSII. Apart from the 5.0- to 7.9-year-old subgroup, long-acting insulin analogues were associated with a significant loss of height-SDS. Choice of basal insulin regimen might influence height development. CSII appeared to have a favorable effect on growth trajectories. All therapies were associated with an increase of BMI-SDS, most evident in females.

Weekly Insulin Becoming a Reality

Insulin was first isolated in 1921 and developed as a therapeutic agent in the 1920s. The initial crude preparations were injected multiple times daily because of their short duration of action. Consequently, there were many attempts to develop insulin preparations with prolonged biological availability in the hope that less frequent once-daily administration would be feasible (1). A host of such preparations were introduced, including protamine insulin, protamine zinc insulin, surfen insulin, globin insulin, iso-insulin, isophane insulin (NPH), and insulin zinc suspensions (lente insulins) (1) (Fig. 1). The goal was mainly to reduce the number of injections and thus the patient burden. Yet, with the development of a radioimmunoassay for insulin (2), it became apparent that physiologic insulin secretion involved two components: meal-related insulin secretion with postprandial spikes and basal insulin secretion that remains relatively constant with some minor pulsatility (3). Subsequently, as modern insulin therapy evolved, facilitated by patient self-monitoring of blood glucose (4,5), it became apparent that the inherent peaks in basal insulin preparations, such as with the nonsoluble NPH or lente insulins, created risk of hypoglycemia, especially if the insulin vials were not correctly rolled to create a proper suspension. Moreover, these insulins did not have sufficiently long duration of action to be used once daily. Consequently, in addition to making them soluble, two of the goals in development of basal insulin analogs, such as insulin glargine and insulin detemir, were to eliminate insulin peaks and to prolong the action to approach 24 h (6,7). Second-generation basal insulin analogs, such as insulin degludec and insulin glargine U300, came with …

846-P: Basal Insulin Management in Inpatients Who Are Not Eating: Is There a Difference between Medical and Surgical Patients?

Background: Guidelines from the 2021 American Diabetes Association recommend basal or basal plus correctional insulin dosing for non-critically ill hospitalized patients with poor oral intake or are nil per os (NPO). The recommended adjustment is 75-80% of long-acting basal insulin administered perioperatively. The aim of this study was to build on the current data available to determine the optimal management of insulin detemir dosing between medicine and surgery patients who were unable to eat. Methods: This was a retrospective single-center observational study between January and December 2019 that included patients with type 2 diabetes and confirmed NPO status receiving insulin detemir. To determine best practices of long-acting insulin management, 100%, 80-33%, and 0% insulin detemir dosing in medical and surgical patients were evaluated. The primary endpoint was incidence of hypoglycemia (&amp;lt;70 mg/dL) after insulin dose adjustment. Secondary endpoints were incidence of severe hypoglycemia (&amp;lt;40 mg/dL) and hyperglycemia (&amp;gt;180 mg/dL) after insulin dose adjustment. Results: Of the 100 adult patients who met the criteria, there were no incidences of hypoglycemia or severe hypoglycemia regardless of insulin detemir dose adjustment in either medical or surgical patients. In the medicine group, hyperglycemia occurred in 23/67 (34.3%), 2/6 (33.3%), 4/12 (33.3%) for 100%, 80-33%, and 0% insulin dose adjustments, respectively. In the surgery group, hyperglycemia occurred in 8/12 (66.7%) in patients receiving 100% insulin detemir dosage with no notable outcomes in the remaining 3 patients. Conclusions: There was no incidence of hypoglycemia or severe hypoglycemia between medical and surgical patients, regardless of insulin detemir dose adjustment. A numerically higher incidence of hyperglycemia was observed in patients receiving 100% insulin detemir in both medicine and surgery patients. Further education is planned to reduce hyperglycemia. Disclosure J. Sacdal: None. H. A. Habib: None. E. Cheon: None. E. Oh: None.