Core pharmacology

Class Group

SGLT2 Inhibitors

Legacy Cicm Level

Level 3

Introduction

Dapagliflozin
Empagliflozin
Ertugliflozin

Indications Uses

1. treatment of non-insulin-dependent
(type II) diabetes mellitus
2. risk reduction in cardiovascular events, heart failure and kidney disease progression, even without diabetes

Chemical Pharmaceutics

synthetic glycoside analogs that are chemically designed to resemble the naturally occurring glucose molecules but with modifications to inhibit glucose reabsorption

Presentation

single medications or in combination with metformin or with gliptins

Main Action

reduction of blood glucose levels

Mechanism of action

Binding and blocking SGLT2 (Sodium-Glucose Co-Transporter 2) protein in proximal tubule of kidney. Results in:
- Reduced Renal glucose reabsorption
- Increased glucose excretion in urine

Onset Peak Duration

Onset variable
Peak 1-2hrs
Duration 24 hrs

Physiological effects

Metabolic:
- Reduced glucose levels and may improve insulin sensitivity in peripheral tissues
- Weight loss, lower TG, inc HDLc

CVS:
- Lower blood pressure due to fluid loss and potential improvements in vascular function
- Cardio protective (mainly Dapa and Empa): reduction in heart failure, major CV events, arrhythmia

Renal:
- mild diuresis (osmotic)
- renoprotective (red albuminuria and progression of diabetic kidney disease

Adverse Effects Toxicity

- Polyuria, UTIs, Dehydration
- Potential risk of AKI
- Ketoacidosis
- Toxicity (rare): excessive fluid loss and electrolyte imbalances

Absorption

Rapid
PO BA: 60-60%

Protein binding

90-99% PB

Volume of distribution

50-100L
Dapa: 118L Empa: 74L

Metabolism

Liver (phase 1 and 2 enzymes)
Dapa, Empa (CYP3A4)
Active and inactive metabolites

Excretion

mostly urine
small fraction feces

Clearance

6-12 L/hr

Half-life

13-16hrs

Special Points

- Renal dose adjustment in eGFR<30
- Risk of dehydeation and electrolyte imbalances

Route And Dose

PO