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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
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Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
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Oral Hypoglycemic Agents: Glinides01:06

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Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
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Glucagon-like Receptor Agonists01:24

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
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Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
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Is insulin the most effective injectable antihyperglycaemic therapy?

J B Buse1, A Peters, D Russell-Jones

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Diabetes, Obesity & Metabolism
|October 18, 2014
PubMed
Summary

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like exenatide and liraglutide offer comparable or superior HbA1c reduction versus insulin glargine in type 2 diabetes. These GLP-1RAs are effective even with very high baseline HbA1c levels.

Keywords:
GLP-1 receptor agonistsHbA1cbasal insulinexenatideliraglutide

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Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Recent guidelines suggest insulin for high HbA1c in type 2 diabetes.
  • Randomized studies showed GLP-1RAs (exenatide OW, liraglutide OD) achieved greater HbA1c reduction than insulin glargine.
  • Baseline HbA1c was approximately 8.3% in prior comparative trials.

Purpose of the Study:

  • To analyze HbA1c, fasting glucose, and weight changes in type 2 diabetes patients treated with exenatide once-weekly or liraglutide once-daily versus insulin glargine.
  • To evaluate treatment efficacy across different baseline HbA1c levels (quartiles).

Main Methods:

  • Post hoc analysis of DURATION-3 and LEAD-5 trials.
  • Descriptive statistics for HbA1c, fasting glucose, weight, and insulin dose changes.
  • ANCOVA model used to assess HbA1c change similarity across baseline HbA1c quartiles.

Main Results:

  • HbA1c reduction and achieving HbA1c <7.0% were similar or greater with GLP-1RAs than glargine across all baseline HbA1c quartiles.
  • Fasting glucose reduction was similar or greater with glargine.
  • GLP-1RAs led to weight loss, while glargine caused weight gain, more pronounced at higher baseline HbA1c.
  • Gastrointestinal events were more frequent with GLP-1RAs.

Conclusions:

  • GLP-1RAs provide at least equivalent HbA1c reduction compared to basal insulin (glargine), regardless of baseline HbA1c.
  • Liraglutide and exenatide once-weekly are viable alternatives to basal insulin for type 2 diabetes, including cases with very high baseline HbA1c (≥9.0%).