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Understanding Diabetes and Treatment Options

Apr 16, 2025

Diabetes Mellitus and Anti-Diabetic Drugs Lecture

Learning Objectives

  • Understand the mechanism of action of various anti-diabetic agents.
  • Learn about individual anti-diabetic drugs.
  • Learn the treatment algorithm for Type 2 Diabetes Mellitus.

Diabetes Mellitus Overview

  • Condition with reduced insulin secretion, action, or both.
  • Insulin normally moves glucose from plasma to tissues.
  • In diabetes, increased plasma glucose due to reduced insulin action or secretion.

Classes of Anti-Diabetic Drugs

  1. Increase Insulin Secretion

    • Sulfonylureas
      • Examples: Glimepiride, Glipizide, Glyburide.
      • Mechanism: Inhibit potassium channels in beta cells, causing depolarization and insulin release.
      • Advantages: Cheap, available.
      • Disadvantages: Can cause hypoglycemia and weight gain.
    • Meglitinide Analogs
      • Example: Repaglinide.
      • Similar to sulfonylureas in mechanism.
    • GLP-1 Agonists
      • Examples: Exenatide, Liraglutide.
      • Mechanism: Mimic incretin hormones, increase insulin secretion only with sufficient glucose levels.
      • Advantages: Cause weight loss, reduce appetite.
      • Disadvantages: Injected, expensive, can cause nausea and vomiting.
    • DPP-4 Inhibitors
      • Examples: Sitagliptin, Saxagliptin.
      • Mechanism: Prevent breakdown of incretins.
      • Advantages: No significant hypoglycemia.
      • Disadvantages: Joint pain, nasopharyngitis.

  2. Reduce Insulin Resistance

    • Metformin
      • First-line treatment for Type 2 Diabetes.
      • Mechanism: Inhibits gluconeogenesis, reduces glucose absorption, increases insulin sensitivity.
      • Advantages: No hypoglycemia, weight loss, reduces complications.
      • Disadvantages: Gastrointestinal side effects, possible Vitamin B12 deficiency.
    • Thiazolidinediones (TZDs)
      • Example: Pioglitazone.
      • Mechanism: Activate PPAR-gamma receptors to increase glucose uptake.
      • Disadvantages: Weight gain, fluid retention, risk of heart failure and fractures.

  3. Reduce Glucose Reabsorption from Kidneys

    • SGLT2 Inhibitors
      • Examples: Canagliflozin, Empagliflozin.
      • Mechanism: Inhibit glucose reabsorption in kidneys.
      • Advantages: Mild weight loss, no hypoglycemia.
      • Disadvantages: Urinary/genital infections, expensive.

  4. Reduce Glucose Absorption from Gastrointestinal Tract

    • Alpha-Glucosidase Inhibitors
      • Examples: Acarbose, Miglitol.
      • Mechanism: Inhibit enzyme breaking down complex carbohydrates.
      • Disadvantages: Gastrointestinal discomfort, flatulence.

Management of Type 2 Diabetes Mellitus

  • Initial steps include education, nutrition, physical activity.
  • Screen for diabetes complications (retinopathy, nephropathy, neuropathy).
  • Start treatment with Metformin.
  • Reassess HbA1c after 3-6 months.
  • Adjust treatment if necessary, possibly adding additional agents or insulin.
  • Goal: Maintain HbA1c < 7%.

Summary

  • Anti-diabetic agents include sulfonylureas, GLP-1 agonists, DPP-4 inhibitors, SGLT2 inhibitors, and alpha-glucosidase inhibitors.
  • Metformin is the first-line treatment for Type 2 Diabetes Mellitus.
  • Understanding drug mechanisms and patient management is crucial due to high prevalence of diabetes.

Full transcript