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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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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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Dipeptidyl Peptidase 4 Inhibitors01:23

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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Insulin: Dosing Regimen and Adverse Effects01:16

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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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Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
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Insulin Formulations: Types and Delivery01:27

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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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Insulin degludec + liraglutide: a complementary combination.

K Stinkens1, B Peene1, C Mathieu1

  • 1a Department of Endocrinology , UZ Leuven, UZ Gasthuisberg , Leuven , Belgium.

Expert Opinion on Biological Therapy
|August 4, 2016
PubMed
Summary

A new combination therapy for type 2 diabetes mellitus, combining basal insulin degludec and glucagon-like peptide-1 analogue liraglutide, offers improved glycemic control with reduced hypoglycemia and weight gain.

Keywords:
DegludecIDegLiraLiraglutidetype 2 diabetes mellitus

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Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) management is complex, requiring control of glycemia, weight, and cardiovascular risk factors.
  • Progressive nature of T2DM necessitates therapy intensification, often involving insulin.
  • Clinical inertia delays insulin initiation, hindering glycemic target achievement in many patients.

Purpose of the Study:

  • To review the fixed-ratio combination of basal insulin degludec and glucagon-like peptide-1 analogue liraglutide for T2DM.
  • To discuss the rationale and clinical trial evidence (DUAL I, II, V) for this combination therapy.

Main Methods:

  • Review of published Phase III clinical trials (DUAL I, II, V).
  • Analysis of efficacy and safety data for insulin degludec/liraglutide combination.

Main Results:

  • The combination therapy provides robust glycemic control.
  • It is associated with a low risk of hypoglycemia.
  • It leads to less weight gain or even weight loss.

Conclusions:

  • Insulin degludec/liraglutide fixed-ratio combination is an attractive strategy for T2DM.
  • It simplifies treatment initiation or intensification where basal insulin is needed.
  • Offers a favorable profile for glycemic control, hypoglycemia risk, and weight management.