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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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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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Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

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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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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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Oral Hypoglycemic Agents: Sulfonylureas01:17

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Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
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SGLT-2 Inhibitors: Focus on Dapagliflozin.

Zoya Siddiqui1, Somar Hadid1, William H Frishman2

  • 1From the School of Medicine, New York Medical College, Valhalla, NY.

Cardiology in Review
|April 26, 2024
PubMed
Summary
This summary is machine-generated.

Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, effectively manages type 2 diabetes, heart failure, and chronic kidney disease. Its unique action on SGLT-2 transporters offers significant patient benefits beyond glycemic control.

Keywords:
DapagliflozinHeart FailureSGLT-2 InhibitorsType 2 Diabetes Melltius

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Area of Science:

  • Pharmacology and Therapeutics
  • Cardiology
  • Nephrology

Background:

  • Dapagliflozin, initially for type 2 diabetes, now has expanded indications for heart failure and chronic kidney disease.
  • Sodium-glucose cotransporter-2 (SGLT-2) inhibitors play a crucial role in managing cardiometabolic and renal diseases.
  • The drug's efficacy extends beyond glycemic control, impacting cardiovascular and renal health.

Purpose of the Study:

  • To review the expanded therapeutic applications of dapagliflozin.
  • To elucidate the mechanism of action and pharmacokinetic profile of dapagliflozin.
  • To compare dapagliflozin's efficacy and safety with other SGLT-2 inhibitors.

Main Methods:

  • Review of clinical trial data and pharmacokinetic studies.
  • Comparative analysis of dapagliflozin with other SGLT-2 inhibitors like empagliflozin and canagliflozin.
  • Examination of adverse effects and contraindications.

Main Results:

  • Dapagliflozin demonstrates efficacy in glycemic control without hypoglycemia risk.
  • It shows potential superiority in heart failure prevention compared to some other SGLT-2 inhibitors.
  • Pharmacokinetic profile shows rapid absorption, an 18-hour duration, and minimal metabolism.

Conclusions:

  • Dapagliflozin is a pivotal medication for improving patient outcomes in diabetes, heart failure, and kidney disease.
  • Understanding its benefits, limitations, and adverse effects is crucial for clinical decision-making.
  • Its mechanism involves competitive binding to SGLT-2, preventing glucose and sodium reabsorption.