• Class: SGLT2 Inhibitor

• Mechanism of Action:

  • Inhibits Sodium–Glucose Co-Transporter-2 (SGLT2) in proximal renal tubules.

  • ↓ Glucose reabsorption → ↑ Urinary glucose excretion → ↓ Blood glucose.

• Pharmacological Effects:

  • Lowers fasting and postprandial glucose

  • Promotes mild weight loss

  • Mild BP reduction (osmotic diuresis).

• Uses:

  • Type 2 Diabetes Mellitus (T2DM)

  • Heart failure with reduced EF (HFrEF)

  • Chronic kidney disease (CKD).

• Adverse Effects:

  • Genital/urinary tract infections (due to glycosuria)

  • Polyuria, dehydration, hypotension

  • Euglycemic diabetic ketoacidosis (rare).

• Class: DPP-4 Inhibitor

• Mechanism of Action:

  • Inhibits Dipeptidyl Peptidase-4 (DPP-4) enzyme.

  • ↑ Levels of incretin hormones (GLP-1, GIP).

  • ↑ Glucose-dependent insulin secretion & ↓ Glucagon secretion.

• Pharmacological Effects:

  • Lowers postprandial glucose

  • Weight-neutral.

• Uses:

  • Type 2 Diabetes Mellitus (as monotherapy or with metformin/others).

• Adverse Effects:

  • Nasopharyngitis, headache

  • Rare: Pancreatitis, hypersensitivity (Stevens-Johnson syndrome).

• Class: Biguanide

• Mechanism of Action:

  • Inhibits hepatic gluconeogenesis

  • ↑ Peripheral glucose uptake (via AMP-activated protein kinase – AMPK activation)

  • ↓ Intestinal glucose absorption.

• Pharmacological Effects:

  • Decreases fasting plasma glucose

  • Improves insulin sensitivity

  • Weight neutral / modest weight loss

  • No hypoglycemia (when used alone).

• Uses:

  • First-line drug for Type 2 Diabetes Mellitus

  • PCOS (off-label).

• Adverse Effects:

  • GI upset (nausea, diarrhea)

  • Vitamin B12 deficiency (long-term)

  • Lactic acidosis (rare, but serious; avoid in renal/hepatic impairment).

• Rationale:

  • Metformin → ↓ Hepatic glucose production

  • Sitagliptin → ↑ Insulin secretion, ↓ Glucagon

  • Dapagliflozin → ↑ Urinary glucose excretion

  • Together: Complementary actions → better glycemic control.

• Clinical Use:

  • T2DM patients uncontrolled with monotherapy/dual therapy.

• Precautions:

  • Monitor renal function (all three require dose adjustments in CKD).

  • Risk of hypoglycemia when combined with sulfonylureas/insulin.

Features:

Manages blood sugar in type 2 diabetes

Improves insulin secretion & sensitivity

Provides prolonged glucose control

Lowers risk of diabetes complication