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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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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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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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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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Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
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DPP-4 inhibitors: focus on safety.

Sri Harsha Tella1, Marc S Rendell

  • 1Creighton Diabetes Center , 601 North 30th Street, Omaha, NE 68131 , USA.

Expert Opinion on Drug Safety
|December 10, 2014
PubMed
Summary

Dipeptidyl peptidase-4 inhibitors (DPP-4-i) offer a safe anti-hyperglycemic option with a low risk of hypoglycemia. While concerns about pancreatitis and cardiac events persist, large trials show no increased risk with DPP-4 inhibitors.

Keywords:
alogliptindipeptidyl peptidase -4 inhibitorsglucagon-like polypeptide-1linagliptinsaxagliptinsitagliptinvildagliptin

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Area of Science:

  • Pharmacology
  • Endocrinology
  • Internal Medicine

Background:

  • Dipeptidyl peptidase-4 inhibitors (DPP-4-i) selectively inhibit DPP-4, increasing incretin hormone levels.
  • Incretins influence insulin and glucagon release, gastric emptying, and satiety.
  • This review focuses on the safety profile of DPP-4 inhibitors.

Purpose of the Study:

  • To review the safety issues associated with dipeptidyl peptidase-4 inhibitors (DPP-4-i).

Main Methods:

  • Literature search using PubMed with keywords for DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin) and related drug classes.
  • Inclusion of personal clinical trial experience with DPP-4 inhibitors.
  • Analysis of data regarding drug interactions, renal excretion, and adverse events.

Main Results:

  • DPP-4 inhibitors exhibit varied chemical structures and metabolic pathways (e.g., saxagliptin's CYP450 metabolism, linagliptin's entero-hepatic excretion).
  • Concerns regarding congestive heart failure (e.g., SAVOR TIMI trial) and pancreatitis/pancreatic cancer have been investigated.
  • Large randomized trials have not demonstrated an increased risk of pancreatitis or pancreatic cancer with DPP-4 inhibitors; cutaneous adverse effects are infrequent.

Conclusions:

  • DPP-4 inhibitors are a valuable addition to anti-hyperglycemic therapies, particularly for elderly patients and those with cardiac conditions due to a low incidence of hypoglycemia.
  • Evidence suggests potentially lower cardiac risk compared to sulfonylureas.
  • Ongoing trials, like the CAROLINA Trial, aim to provide conclusive data on cardiac safety compared to other antidiabetic agents.