New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin

Frias, Patrick F.; Frías, Juan P.

doi:10.1007/s11892-017-0926-8

Cited by 15 publications

(8 citation statements)

References 45 publications

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“…Those available in East Africa are shown in Table 3 . The perceived advantages of using premixed insulin over a self-mixed insulin include the increased accuracy of dosage, efficacy, and patient convenience, which may translate to increased compliance and thus better long-term control of diabetes [ 67 , 68 ].…”

Section: Methodology and Evidencementioning

confidence: 99%

EADSG Guidelines: Insulin Therapy in Diabetes

et al. 2018

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Executive Summary and Recommendations A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A).Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A).Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin. Two or three premixed insulin injections per day may be used (A).The _target glycated hemoglobin A1c (HbA1c) for all children with T1DM, including preschool children, is recommended to be < 7.5% (< 58 mmol/mol). The _target is chosen aiming at minimizing hyperglycemia, severe hypoglycemia, hypoglycemic unawareness, and reducing the likelihood of development of long-term complications (B).For patients prone to glycemic variability, glycemic control is best evaluated by a combination of results with self-monitoring of blood glucose (SMBG) (B).Indications for exogenous insulin therapy in patients with type 2 diabetes mellitus (T2DM) include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy (B).In T2DM patients, with regards to achieving glycemic goals, insulin is considered alone or in combination with oral agents when HbA1c is ≥ 7.5% (≥ 58 mmol/mol); and is essential for treatment in those with HbA1c ≥ 10% (≥ 86 mmol/mol), when diet, physical activity, and other antihyperglycemic agents have been optimally used (B).The preferred method of insulin initiation in T2DM is to begin by adding a long-acting (basal) insulin or once-daily premixed/co-formulation insulin or twice-daily premixed insulin, alone or in combination with glucagon-like peptide-1 receptor agonist (GLP-1 RA) or in combination with other oral antidiabetic drugs (OADs) (B).If the desired glucose _targets are not met, rapid-acting or short-acting (bolus or prandial) insulin can be added at mealtime to control the expected postprandial raise in glucose. An insulin regimen should be adopted and individualized but should, to the extent possible, closely resemble a natural physiologic state and avoid, to the extent possible, wide fluctuating glucose levels (C).Blood glucose monitoring is an integral part of effective insulin therapy and should not be omitted in the patient’s care plan. Fasting plasma glucose (FPG) values should be used to titrate basal insulin, whereas both FPG and postprandial glucose (PPG) values should be used to titrate mealtime insulin (B).Metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when compared with insulin alone (C).Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia (D).Analogue insulin is as effective as human insulin but is a...

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Section: Methodology and Evidencementioning

confidence: 99%

EADSG Guidelines: Insulin Therapy in Diabetes

et al. 2018

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“…14 Briefly, 48 T1D subjects, grouped in two cohorts (cohort 1 [n = 24]: 22 males, age = 44 -10 years; BMI = 25.4 -2.5 kg/m 2 ; cohort 2 [n = 24]: 24 males, age = 41 -12 years; BMI = 26.0 -2.1 kg/m 2 ), received once-daily sc administrations of either 0.4 (cohort 1) or 0.6 U/kg (cohort 2) Gla-300 for 8 days in one treatment period and Deg-100 for 8 days in the other. A 30-h euglycemic clamp procedure was performed after each 8-day period with blood samples collected at 0, 1,2,4,6,8,10,12,14,16,20,24,28, and 30 h after dosing on day 8. A validated radioimmunoassay was used for measurement of total insulin concentration, accounting for both bound and unbound insulins to albumin, with a lower limit of quantification of 12 lU/mL.…”

Section: Development Of Insulin Deg-100 Pk Modelmentioning

confidence: 99%

“…Ins-AUC 0À24 h, Deg-100 GIR-AUC 0À24 h, Gla-300 = Ins-AUC 0À24 h, Gla-300 (1) formulations and injection schedules, two different basal insulin titration rules were implemented, with titration rules A and B derived from Home et al 11 and Heller et al, 35 respectively. In particular, virtual patients were titrated to their optimal individual dose until they reached the glucose _target, which is 80-130 mg/dL for titration rule A and 70-89 mg/dL for titration rule B (more details about titration rules are reported in Supplementary Table S1).…”

Section: Gir-auc 0à24 H Deg-100mentioning

confidence: 99%

“…In the last decades, advances have been made in developing new basal and prandial insulin analogues aiming to mimic endogenous insulin secretion of healthy subjects. In particular, second-generation long-acting (basal) insulin analogues exhibit flatter pharmacokinetic (PK) and pharmacodynamic (PD) profiles, with an insulin dosing frequency not inferior than once daily, thus _targeting an action duration exceeding 24 h. 1,2 Insulin glargine 300 U/mL (Gla-300) and degludec 100 U/mL (Deg-100) represent the second generation of long-acting insulin analogues, with respect to insulin glargine 100 U/mL (Gla-100) and insulin detemir 100 U/mL (Det-100), respectively, showing a more prolonged and stable insulin profile over 24 h. This is achieved through different mechanisms of protraction. 3,4 Insulin Gla-300, similarly to Gla-100, rapidly precipitates at the injection site, due to a low solubility at physiological pH, then, it is absorbed into plasma with a slower rate than Gla-100 thanks to its higher concentrated formulation.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In SilicoHead-to-Head Comparison of Insulin Glargine 300 U/mL and Insulin Degludec 100 U/mL in Type 1 Diabetes

Schiavon

Visentin

Giegerich

et al. 2020

Diabetes Technology & Therapeutics

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Background: Second-generation long-acting insulin glargine 300 U/mL (Gla-300) and degludec 100 U/mL (Deg-100) provide novel basal insulin therapies for the treatment of type 1 diabetes (T1D). Both offer a flatter pharmacokinetic (PK) profile than the previous generation of long-acting insulins, thus improving glycemic control while reducing hypoglycemic events. This work describes an in silico head-to-head comparison of the two basal insulins on 24-h glucose profiles and was used to guide the design of a clinical trial. Materials and Methods: The Universities of Virginia (UVA)/Padova T1D simulator describes the intra-/ interday variability of glucose-insulin dynamics and thus provides a robust bench-test for assessing glucose control for basal insulin therapies. A PK model describing subcutaneous absorption of Deg-100, in addition to the one already available for Gla-300, has been developed based on T1D clinical data and incorporated into the simulator. One hundred in silico T1D subjects received a basal insulin dose (Gla-300 or Deg-100) for 12 weeks (8 weeks uptitration, 4 weeks stable dosing) by morning or evening administration in a basal/bolus regimen. The virtual patients were uptitrated to their individual doses with two different titration rules. Results: The last 2-week simulated continuous glucose monitoring data were used to calculate various outcome metrics for both basal insulin treatments, with primary outcome being the percent time in glucose _target (70-140 mg/dL). The simulations show no statistically significant difference for Gla-300 versus Deg-100 in the main endpoints. Conclusions: This work suggests comparable glucose control using either Gla-300 or Deg-100 and was used to guide the design of a clinical trial intended to compare second-generation long-acting insulin analogues.

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