Pharmacological Therapy in Type 2 Diabetes

1. Biguanides

• Drug: Metformin

• Mechanism of Action: Decreases hepatic insulin resistance

• Glycemic Efficacy: High Basal glycemia

• Cardiovascular Effects: Potential benefit in atherosclerotic CVD

• Risk of Hypoglycemia: Neutral

• Effect on Weight: Neutral/Slight weight loss

• Side Effects/Contraindications:

  • Gastrointestinal side effects (nausea, diarrhea)

  • Vitamin B12 deficiency

  • Lactic acidosis (rare)

  • Contraindicated in hepatic failure

• Route of Administration: Oral

2. SGLT2 Inhibitors

• Drugs: Dapagliflozin, Canagliflozin, Empagliflozin

• Mechanism of Action: Inhibits SGLT2, leading to urinary excretion of glucose

• Glycemic Efficacy: Intermediate Postprandial glycemia

• Cardiovascular Effects: Benefit in heart failure and atherosclerotic CVD

• Risk of Hypoglycemia: Reduces the progression of CKD

• Effect on Weight: Neutral, Weight loss

• Side Effects/Contraindications:

  • Risk of diabetic ketoacidosis

  • Genitourinary infections

  • Risk of hypovolemia, hypotension

  • Fournier's risk of gangrene

  • Risk of fractures and amputations (canagliflozin)

  • ↑ LDL-Cholesterol

• Route of Administration: Oral

3. GLP-1 Receptor Agonists

• Drugs: Exenatide, Dulaglutide, Liraglutide, Lixisenatide, Semaglutide

• Mechanism of Action:

  • Stimulates insulin secretion (glucose-dependent)

  • Inhibits appetite

  • Inhibits glucagon secretion (glucose-dependent)

  • Delays gastric emptying

• Glycemic Efficacy: High Postprandial glycemia

• Cardiovascular Effects: Neutral (Lixisenatide)

• Risk of Hypoglycemia: Neutral

• Effect on Weight: Weight loss

• Side Effects/Contraindications:

  • Risk of medullary thyroid neoplasm

  • Gastrointestinal side effects (nausea, vomiting, diarrhea)

  • Possible injection site reactions

  • ? Acute pancreatitis

• Route of Administration: Injection s.c once weekly/Oral (Semaglutide)

4. DPP4 Inhibitors

• Drugs: Sitagliptin, Saxagliptin, Linagliptin

• Mechanism of Action: Inhibits DPP4 and endogenous GLP-1 degradation

• Glycemic Efficacy: Intermediate Postprandial glycemia

• Cardiovascular Effects: Potential risk for heart failure (Saxagliptin)

• Risk of Hypoglycemia: Neutral

• Effect on Weight: Neutral

• Side Effects/Contraindications:

  • Potential risk of acute pancreatitis

  • Joint pain

• Route of Administration: Oral

5. Alpha Glucosidase Inhibitors

• Drugs: Acarbose, Miglitol, Voglibose

• Mechanism of Action: Inhibits alpha-glucosidase enzymes

• Glycemic Efficacy: Intermediate Postprandial glycemia

• Cardiovascular Effects: Neutral

• Risk of Hypoglycemia: Neutral

• Effect on Weight: Neutral

• Side Effects/Contraindications: Gastrointestinal side effects (flatulence, diarrhea)

• Route of Administration: Oral

6. Sulfonylureas

• Drugs: Glibenclamid, Gliclazid, Glimepirid

• Mechanism of Action: Stimulates insulin secretion independent of glucose

• Glycemic Efficacy: High Basal and postprandial glycemia

• Cardiovascular Effects: Risk ↑

• Risk of Hypoglycemia: Weight gain

• Side Effects/Contraindications: Contraindicated in hepatic failure

• Route of Administration: Oral

7. Glinides

• Drugs: Repaglinide, Nateglinide

• Mechanism of Action: Stimulates insulin secretion independent of glucose

• Glycemic Efficacy: Intermediate Postprandial glycemia

• Cardiovascular Effects: Moderate

• Risk of Hypoglycemia: Weight gain

• Side Effects/Contraindications: Contraindicated in hepatic failure

• Route of Administration: Oral