- Enhance peripheral action of insulin
- ↑ rate of anaerobic glycolysis and ↓ rate of gluconeogenesis
- Inhibit intestinal absorption and ↓ peripheral utilization of glucose

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

CVS:
- ↓ intestinal absorption of glucose, folate, vit B12
- no effect on gastric motility
- ↑ utilization of glucose and cause weight loss
Metabolic/Other:
- ↑ sensitivity to peripheral actions of insulin by ↑ no of low affinity binding sites (RBC, Adipocytes, hepatocytes, sk. Muscle)
- inhibits metabolism of lactate and ↓ plasma TG, cholesterol, pre-beta lipoprotein

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

Slowly absorbed from small intestine
PO BA: 50-60%

Rapid
PO BA: 60-60%

Not protein bound

90-99% PB

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

No metabolites

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

Unchanged in urine

mostly urine
small fraction feces

> GFR (Active tubular secretion)

6-12 L/hr

Elimination half life 1.7-4.5 hrs

13-16hrs

- Does not cause hypoglycaemia when used on its own
- GI disturbances
- Lactic acidosis (rare)

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

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

Biguanides

SGLT2 Inhibitors

treatment of non-insulin-dependent
(type II) diabetes mellitus

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

Dapagliflozin
Empagliflozin
Ertugliflozin

Level 3

Level 3

Hypoglycaemia

reduction of blood glucose levels

Onset variable
Peak 1-2hrs
Duration 24 hrs

As 500/850 mg tablets of metformin hydrochloride
MR also available.

single medications or in combination with metformin or with gliptins

PO
1-3gm daily in divided doses

PO

Not recommended in renal impairment

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