Levemir

Manufactured by Novo Nordisk

Sourced in Denmark

Levemir is a long-acting insulin analog used to control blood sugar levels in individuals with diabetes. It is administered through subcutaneous injection and provides a steady, continuous supply of insulin over an extended period. Levemir is designed to help maintain stable blood glucose levels throughout the day and night.

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Lab products found in correlation

Novorapid, by Novo Nordisk (3 mentions) Novomix 30, by Novo Nordisk (2 mentions) Pyridoxamine dihydrochloride monohydrate, by Tokyo Chemical Industry (1 mentions) Salicylate sodium salicylate, by Merck Group (1 mentions) Humulin r u 100, by Eli Lilly (1 mentions) Insulin lispro, by Eli Lilly (1 mentions) Novolin n, by Novo Nordisk (1 mentions) Lantus, by Sanofi (1 mentions) Humalog, by Eli Lilly (1 mentions) Glargine, by Sanofi (1 mentions) Glulisine, by Sanofi (1 mentions) Aspart, by Novo Nordisk (1 mentions) Actrapid, by Novo Nordisk (1 mentions) Lispro, by Eli Lilly (1 mentions) Degludec, by Novo Nordisk (1 mentions) Tresiba, by Novo Nordisk (1 mentions) Novolin r, by Novo Nordisk (1 mentions)

9 protocols using levemir

Diabetic Mouse Model Treatments

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Pyridoxamine-dihydrochloride-monohydrate (4-aminomethyl-3-hydroxy-2-methyl-5-oxymethylpyridinedihydrochloride) was purchased from Tokyo Chemical Industry Co., Japan. The pyridoxamine dihydrochloride was given at 1 g/L (~200 mg/kg/day) in the drinking water from 4 to 20 weeks of age for 16 weeks, resulting in the serum concentration at 0.42 μM (<0.03 μM in nontreated mice). Salicylate (sodium salicylate, Sigma-Aldrich, Japan) was given at 3 g/kg in their diets, yielding the serum concentration at 102.6 μM (not detected in nontreated mice). For the insulin treatment group, a long-acting insulin analog of insulin detemir (Levemir, Novo Nordisk) was subcutaneously injected twice a day at the dose of 2 units/kg body weight.
The following five animal groups were subjected to phenotypic analyses: (1) nondiabetic control (n = 8), (2) diabetic mice without treatment (n = 19), (3) diabetic mice with insulin treatment (n = 8), (4) diabetic mice with salicylate treatment (n = 12), and (5) diabetic mice with pyridoxamine treatment (n = 15).

Abouzed T.K., Munesue S., Harashima A., Masuo Y., Kato Y., Khailo K., Yamamoto H, & Yamamoto Y. (2016). Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy. Journal of Diabetes Research, 2016, 1786789.

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Intranasal Insulin Delivery Study

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Participants were randomly assigned to receive a daily dosage of 40 IU of insulin detemir (20 IU detemir b.i.d.), 40 IU of regular insulin (20 IU regular insulin b.i.d.), or placebo (saline b.i.d.) for 4 months. Saline, regular insulin (Humulin R U-100, Eli Lilly and Co.), or insulin detemir (Levemir^®; Novo Nordisk, Princeton, New Jersey) was administered 30 minutes after breakfast and dinner with a ViaNase nasal delivery device (Kurve Technology, Bothell, WA) designed to deliver drugs to the paranasal sinuses containing the olfactory cleft region, a dispersion pattern postulated to maximize transport to the central nervous system compared with more diffuse dispersion, potentially due to vascular characteristics of this region [17, 18 (link)]. The Kurve device uses a controlled particle dispersion platform that produces a vertical distribution of particles between 15–20μm, a size shown to minimize peripheral deposition (http://www.kurvetech.com/pdf/ONdrugDelivery-Kurve.pdf). This device had been used successfully in a previous 4-month study of intranasal insulin [10 (link)]. Participants inserted a needle-less syringe containing the measured amount of insulin into the device chamber. The device then released a metered dose of saline or insulin into a chamber covering the participant’s nose over a 2-minute period, which was inhaled by breathingregularly.

Craft S., Claxton A., Baker L.D., Hanson A.J., Cholerton B., Trittschuh E.H., Dahl D., Caulder E., Neth B., Montine T.J., Jung Y., Maldjian J., Whitlow C, & Friedman S. (2017). Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer’s Disease Biomarkers: A Pilot Clinical Trial. Journal of Alzheimer's Disease, 57(4), 1325-1334.

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Comparing Insulin Regimens for Diabetes

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Main exposures in the present study were one of four insulin regimens: regimen 1 (insulin glargine, once daily), regimen 2 (biphasic insulin, twice daily), regimen 3 (biphasic insulin, three times daily) and regimen 4 (rapid‐acting insulin analog, three times daily; and long‐acting insulin, once daily), based on the frequency of insulin injection9, 10, 11. These specific regimens included the largest number of patients among those receiving one to four insulin injections daily. The rapid‐acting insulin analog used was insulin aspart (Novo Rapid^®; Novo Nordisk, Bagsværd, Denmark) or insulin lispro (Humalog^®; Eli Lilly, Indianapolis, IN, USA) in the present study. Long‐acting insulin included neutral protamine Hagedorn (Novolin N^®; Novo Nordisk), insulin neutral protamine lispro (Humalog N^®; Eli Lilly), insulin detemir (Levemir^®; Novo Nordisk) or insulin glargine (Lantus^®; Sanofi‐Aventis, Paris, France). Biphasic insulin included lispro mix 75/25 (75% insulin lispro protamine suspension and 25% of insulin lispro; Eli Lilly), lispro mix 50/50 (50% insulin lispro protamine suspension and 50% of insulin lispro; Eli Lilly) or aspart 30/70 mix (70% protamine‐crystallized aspart and 30% soluble insulin aspart; Novo Nordisk).

Fujita N., Yamamoto Y., Hayashino Y., Kuwata H., Okamura S., Iburi T., Furuya M., Kitatani M., Yamazaki S., Ishii H., Tsujii S., Inagaki N, & Fukuhara S. (2017). Real‐life glycemic control in patients with type 2 diabetes treated with insulin therapy: A prospective, longitudinal cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT 9]). Journal of Diabetes Investigation, 9(2), 294-302.

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Glycemic Control with Biphasic Insulin Aspart

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The A₁ chieve study[11 (link)] was an international, open-label, prospective, non-interventional study to determine the safety and effectiveness of BIAsp 30 (NovoMix 30^®, Novo Nordisk), insulin detemir (Levemir^®, Novo Nordisk) and insulin aspart (NovoRapid^®, Novo Nordisk), alone or in combination, in routine clinical care. In this sub-analysis, T2D patients from India who switched from basal-bolus insulin therapy or basal insulin (NPH insulin or insulin glargine) to biphasic insulin aspart 30 were included. Patients were recruited at 621 centers in India between May 2009 and December 2010. Insulin therapy was switched at the consulting physicians’ discretion and subsequent changes in dose, frequency and use of oral glucose-lowering drugs (OGLDs) were directed by the physician in routine clinical care. There were no pre-defined study procedures and all assessments were made by the physicians. This study was approved by the local ethics committee. The study drug was commercially available and prescribed in accordance with local regulations.

Bhattacharyya A., Shetty R., Rajkumar C, & Bantwal G. (2014). Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A1 chieve study. Indian Journal of Endocrinology and Metabolism, 18(4), 480-485.

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BIAsp 30 Therapy in Indian T2D

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A₁chieve was a 24-week, prospective, open-label, non-interventional study conducted across four continents to examine the safety and effectiveness of BIAsp 30 (NovoMix^® 30, Novo Nordisk A/S), insulin detemir (Levemir^®, Novo Nordisk A/S) and insulin aspart (NovoRapid^®, Novo Nordisk A/S), alone or in combination with basal insulin, in clinical practice.[10 (link)] This subgroup analysis was performed in Indian patients with T2D who changed therapy to BIAsp 30 from BHI.
Patients were recruited from 621 centers in India between May 2009 and December 2010. The decision to switch from BHI to BIAsp 30 therapy was made by the consulting physicians who also decided the dose and dosing frequency throughout the study. BIAsp 30 was available locally and was used in accordance with the locally approved label. Concomitant oral glucose-lowering drugs (OGLDs) were also permitted at the discretion of the physician.
Data were recorded in the standard case report forms from the physicians’ notes and the patients’ diaries and blood glucose meters.

Das A.K., Kalra S., Akhtar S., Shetty R, & Kumar A. (2015). Clinical experience of switching from biphasic human insulin to biphasic insulin aspart 30 in Indian patients with type 2 diabetes in the A1chieve study. Indian Journal of Endocrinology and Metabolism, 19(1), 110-115.

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Insulin Detemir Expiry Evaluation

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Insulin detemir (IDet), trademarked as Levemir® and manufactured by Novo Nordisk, was obtained as 3 mL vials, 100U/mL (14.2 mg/mL), for FlexTouch® pens, as a gift from the Independent Diabetes Trust. IDet excipients list includes 65.4 μg/mL zinc, 2.06 mg/mL m-cresol, 16.0 mg/mL glycerol, 1.80 mg/mL phenol, 0.89 mg/mL Na 2 HPO 4 •2H 2 O and 1.17 mg/mL NaCl. HCl and NaOH may have been added by the manufacturer to adjust pH to 7.4 [20] . These preparations included expired samples (2013, 2015, 2016, 2017) as well as an in-date batch (2020). While not in use, all IDet preparations were refrigerated at ~5 °C. All experiments involving expiry of samples were carried out over a 4 month period in Summer 2018.
Eight other in-date insulins were also screened to assess temperature dependence, but only for single dose concentrations. These were Human Recombinant (Novorapid®, Novo Nordisk), Bovine and Porcine (Hypurin®, Wockhardt), Aspart (Actrapid®, Novo Nordisk), Glulisine (Apidra®, Sanofi), Lispro (Humalog®, Lilly), Glargine (Lantus®, Sanofi) and Degludec (Tresiba®, Novo Nordisk).

Beji O., Gillis R.B., Dinu V., Jiwani S.I., Gyasi-Antwi P., Fisk I.D., Meal A., Morgan P.S., Harding S.E., Huang S., Agugini G., Fedele F, & Adams G.G. (2020). Exploration of temperature and shelf-life dependency of the therapeutically available Insulin Detemir. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 152.

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Long-term Treatment of Wfs1 Knockout Rats

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Eight-month-old Wfs1 KO and WT rats were used for the long-term treatment paradigm; tested compounds were selected based on the results of the acute screening paradigm (timeline in Supplementary Figure 1). After the baseline IPGTT, animals were randomly allocated to one of the experimental groups below:
i. SAL (WT n = 9, Wfs1 KO n = 10) 0.9% solution.
ii. DA-CH5 (WT n = 8, Wfs1 KO n = 10) 25 nmol/kg.
Treatments were administered for 4 months (daily, s.c.), with follow-up IPGTTs at 10.5 and 12 months. Rats received weekly weigh-ins and monthly base blood sugar level monitoring. Supportive insulin treatment (100 IU/ml, Levemir, Novo Nordisk, Denmark) was initiated in hyperglycemic Wfs1 KO rats; animals with a basal blood glucose level of 10 mmol/l received 1 IU/kg of insulin (twice daily, s.c.). Every subsequent 5 mmol/l increase in blood glucose corresponded to a 1 IU/kg increase in the insulin dose (for e.g., blood glucose 20 mmol/l = 6 IU/kg insulin, twice daily).

Jagomäe T., Gaur N., Seppa K., Reimets R., Pastak M., Plaas M., Kaasik A., Vasar E, & Plaas M. (2023). Treatment with the dual-incretin agonist DA-CH5 demonstrates potent therapeutic effect in a rat model of Wolfram Syndrome. Frontiers in Endocrinology, 14, 1234925.

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Insulin Therapy Management in Pdx1-Hes1 Tg Pigs

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Pdx1-Hes1 Tg pigs required lifelong administration of exogenous insulin. In humans, the magnitude of disruption of metabolic control by diabetes has been reported, even in young infants and neonates.26 (link) However, studies are often limited by difficulties in obtaining control data. To minimize the risk of hypoglycemia and dead in bed syndrome,27 (link) a minimum dose of insulin is given by the injection of short-acting (Novolin R; Novo Nordisk, Bagsvaerd Denmark) and long-acting insulin analogs (Levemir and Tresiba; Novo Nordisk). Additionally, an insulin pump can be used for continuous subcutaneous insulin delivery as an alternative therapeutic strategy.28 (link) To achieve target glycemic control issues associated with insulin therapy, a continuous subcutaneous insulin infusion (CSII) pump (Medtronic MiniMed 620G Insulin pump; Medtronic Inc, Dublin, Ireland) was used for one Pdx1-Hes1 Tg pig. Because the pump weighed approximately 100 g, we used short-acting and long-acting insulin until the pig reached 7 weeks of age and then used an insulin pump thereafter.

Nagaya M., Hasegawa K., Watanabe M., Nakano K., Okamoto K., Yamada T., Uchikura A., Osafune K., Yokota H., Nagaoka T., Matsunari H., Umeyama K., Kobayashi E., Nakauchi H, & Nagashima H. (2020). Genetically engineered pigs manifesting pancreatic agenesis with severe diabetes. BMJ Open Diabetes Research & Care, 8(2), e001792.

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Long-acting Insulin Detemir Protocol

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Long-acting insulin detemir (Levemir, Novo Nordisk) was freshly diluted in NaCl 0.9% and injected s.c. twice per day (1.7 U/kg in the morning, 3.3 U/kg in the evening). Insulin pellets (LinShin Canada Inc., Canada) were implanted s.c.

Damond N., Thorel F., Moyers J.S., Charron M.J., Vuguin P.M., Powers A.C, & Herrera P.L. (2016). Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist. eLife, 5, e13828.

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