I. Indications

  1. Type 2 Diabetes Mellitus Management (second-line or third-line agent)
    1. Reserve for cases where other second-line agents with longer track record (as of 2014) and lesser expense have been exhausted

II. Mechanism

  1. Sodium-Glucose Transporter 2 (SGLT2) acts in the Kidneys to resorb Glucose
  2. SGLT2 Inhibitors allow more Glucose to remain in the urine without reabsorption

III. Preparations

  1. Invokana (Canagliflozin, released 2013)
  2. Farxiga (Dapagliflozin, released 2014)
  3. Ipragliflozin
  4. Empagliflozin (Jardiance, released 2014)

IV. Efficacy

  1. Lowers Hemoglobin A1C up to 1%

V. Advantages

  1. May lower weight up to 4 to 7 pounds (via diuresis)
  2. May lower Blood Pressure by 3-5 mmHg (via similar Mechanism to weight)
  3. Low risk of Hypoglycemia

VI. Disadvantages

  1. See adverse effects below
  2. Expensive ($10 per day or more than $250/month) - similar to Januvia costs
  3. Lower efficacy in moderate to severe renal Impairment

VII. Contraindications

  1. Renal dysfunction
    1. GFR <60 ml/min: Avoid Farxiga (Dapagliflozin)
    2. GFR <45 ml/min: Avoid both Invokana (Canagliflozin) and Empagliflozin (Jardiance)

VIII. Adverse Effects

  1. Urinary Tract Infection
  2. Genital yeast infection
  3. Diuretic effect (may result in dehydration)
  4. LDL Cholesterol increase (4-8 mg/dl)
  5. Hyperkalemia
    1. When used in combination with ACE Inhibitors, Angiotensin Receptor Blockers or Potassium Sparing Diuretics
  6. Bladder Cancer increased risk
    1. Associated only with Farxiga

IX. Dosing

  1. AM dosing is recommended due to Diuretic effect
  2. Taken 30 minutes before first meal of day
  3. Start: 100 mg orally daily
  4. Maximum: 300 mg orally daily
    1. Avoid maximum dose if GFR<60 ml/min

X. Resources

  1. Efficacy and safety of Canagliflozin
    1. http://onlinelibrary.wiley.com/doi/10.1111/dom.12054/pdf

XI. References

Images: Related links to external sites (from Google)

Ontology: Sodium-Glucose Transporter 2 (C1565154)

Definition (MSH) A sodium-glucose transporter that is expressed in the luminal membrane of the PROXIMAL KIDNEY TUBULES.
Concepts Amino Acid, Peptide, or Protein (T116) , Biologically Active Substance(T123)
MSH D051297
Russian НАТРИЙ-ГЛЮКОЗНЫЙ ТРАНСПОРТЕР 2, NATRII-GLIUKOZNYI TRANSPORTER 2, NATRII-GLIUKOZY TRANSPORTER 2, НАТРИЙ-ГЛЮКОЗЫ ТРАНСПОРТЕР 2
Italian Trasportatore sodio-glucosio 2
English Sodium-Glucose Transporter 2, SODIUM GLUCOSE TRANSPORTER 002, Sodium-Glucose Transporter 2 [Chemical/Ingredient], SGLT2 Protein, SLC5A2 Protein, Sodium Glucose Transporter 2
Czech transportér 2 pro sodík a glukosu
Finnish Natrium-glukoosin kuljettaja 2
Japanese ナトリウム-グルコーストランスポーター2, ナトリウム-グルコース輸送体2, グルコースナトリウム輸送体2, ナトリウム-グルコース共輸送体2, ナトリウム-ブドウ糖共輸送体2, グルコース-ナトリウム共輸送体2, ナトリウム依存性グルコース共輸送体2, グルコースナトリウムトランスポーター2
French Transporteur-2 sodium-glucose, Cotransporteur de glucose sodium-dépendant de type 2, SGLT2, Protéine SGLT2, Protéine SLC5A2, Transporteur SGLT2, Transporteur SLC5A2
Swedish Sodium-Glucose Transporter 2
Polish Transporter 2 sodowo-glukozowy
Portuguese Transportador 2 de Glucose-Sódio, Transportador 2 de Sódio-Glucose, Transportador de Glucose-Sódio, 2, Transportador de Sódio-Glucose, 2
German Natrium-Glucose-Transporter 2, SGLT2-Protein, SLC5A2-Protein
Spanish Transportador 2 de Sodio-Glucosa

Ontology: canagliflozin (C2974540)

Concepts Carbohydrate (T118) , Pharmacologic Substance(T121)
MSH C552334
English canagliflozin, CANAGLIFLOZIN, Canagliflozin