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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.
Acarbose and miglitol are...
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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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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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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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The right place for metformin today.

Guntram Schernthaner1, Gerit-Holger Schernthaner2

  • 1Rudolfstiftung Hospital & Medical University of Vienna, Department of Medicine II, Vienna, Austria; Medical University of Vienna, Department of Medicine II, Vienna, Austria.

Diabetes Research and Clinical Practice
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Metformin is a widely used type 2 diabetes drug, effective for lowering HbA1c and aiding weight loss without increasing hypoglycemia risk. Extensive research indicates it significantly reduces all-cause mortality, supporting its guideline-recommended use.

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Area of Science:

  • Endocrinology
  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Metformin is the leading global drug for type 2 diabetes treatment, with over 60 years of established efficacy and safety.
  • Current guidelines universally recommend metformin for newly diagnosed diabetes, either alone or combined with other agents, due to its proven cardiovascular and renal benefits.

Purpose of the Study:

  • To review the established efficacy and safety of metformin in type 2 diabetes management.
  • To examine the evidence supporting metformin's cardiovascular and renal benefits, despite the absence of a placebo-controlled cardiovascular outcome trial.
  • To highlight recent findings on metformin's association with reduced all-cause mortality and explore potential links to cancer outcomes.

Main Methods:

  • Review of existing clinical guidelines and observational studies on metformin use in type 2 diabetes.
  • Analysis of a recent meta-analysis of 26 observational studies involving 815,839 patients.
  • Examination of data regarding metformin's effects on HbA1c, weight, hypoglycemia, cardiovascular outcomes, and all-cause mortality.

Main Results:

  • Metformin effectively lowers HbA1c and promotes weight loss without increasing hypoglycemia risk.
  • Observational studies consistently demonstrate metformin's beneficial effects in patients with coronary heart disease, heart failure, and chronic kidney disease.
  • A meta-analysis revealed that metformin use is linked to a significantly lower rate of all-cause mortality (HR: 0.74; 95% CI: 0.68-0.81).

Conclusions:

  • Metformin remains a cornerstone therapy for type 2 diabetes, recommended by global guidelines for its efficacy and safety.
  • Evidence from observational studies and meta-analyses strongly supports metformin's role in reducing cardiovascular and all-cause mortality.
  • Future research should investigate the relationship between metformin and cancer outcomes, and consider early combination therapy, such as with SGLT-2 inhibitors.