1. A New Modality for Treating Type 2 Diabetes
SGLT-2 Inhibitors
A New Modality for Treating Type 2 Diabetes
David Joffe BSPharm, CDE, Clinical Assistant Professor of Pharmacotherapy and Translational Research
Courtney Glanzrock, PharmD Candidate University of Florida College of Pharmacy

2. SGLT-1 and SGLT-2
Two sodium glucose transporters, cause glucose reabsorption, have been identified: SGLT-1 and SGLT-2
SGLT-2 is found only in the proximal tubule of the kidney, accounts for 90% of the re-absorption of glucose
SGLT-1 is found in the gut and other tissues, account for approximately 10% of glucose reabsorption

3. SGLT-2 Inhibitor - Canagliflozin
Invokana (Canagliflozin) 1st SGLT-2 inhibitor, approved March 2013
Once daily dosing before 1st meal of day, 100mg or 300mg tablets
MOA: Inhibition of SGLT2 reduces reabsorption of glucose in the kidney, resulting in increased urinary glucose excretion, with a consequent lowering of plasma glucose levels as well as weight loss.
Blocks approximately grams of glucose per day from being reabsorbed

4. SGLT2-I

5. SGLT-2 Inhibitor-Canagliflozin
Positive effects: Reduction in body weight and systolic blood pressure
Side effects: Most common: Vaginal yeast infection, urinary tract infection and increased urination. Hypoglycemia (<5%), dehydration, dizziness or fainting, hyperkalemia
Contraindications: Clinicians should not use canagliflozin to treat patients with type 1 diabetes, patients with type 2 diabetes who have increased ketones in their blood or urine, severe renal impairment, end-stage renal disease or patients receiving dialysis

6. SGLT-2 Inhibitor First In Class

7. Canagliflozin Side Effects

8. Canagliflozin Drug Interactions:
UGT Inducers (Rifampin, Phenytoin, Phenobarbitol, Ritonavir)- Decreased canagliflozin, consider increasing dose of canagliflozin
Digoxin- Increased digoxin concentration, monitor levels
Pregnancy Category C
Do Not Use: GFR <30mL/min, end stage renal disease, or patients on dialysis

9. SGLT-2 Inhibitor-Canagliflozin
Pre-Marketing Study Results:
Average decrease in A1C levels 1%
Weight Loss average 5-10 pounds
Decrease in systolic blood pressure approximately 4%
Increase HDL approximately 7.6%
Increase LDL approximately 11.7%
Low risk of hypoglycemia

10. SGLT-2 Inhibitors Pipeline: Empagliglozin (Eli Lilly/Behringer)
Dapagliflozin (AstraZeneca)
Remogliflozin Etabonate (GlaxoSmithKline)
Sergliflozin Etabonate (GlaxoSmithKline)
Tofoglitazone (Roche & Chugal)

11. Comparing Agents Medication Average A1C lowering Hypoglycemic Agent
Weight Gain/Loss
Metformin
1.5% No
Loss
Sulfonylureas
Yes
Gain
Glinides
1-1.5%
SGLT-2 Inhibitors 1%
TZDs %
α-Glucosidase Inhibitor %
Neutral
DPP-4 Inhibitors
0.5-1%

12. References
Berkrot, Bill. "Johnson & Johnson Diabetes Drug Tops Older Therapies in Studies." Reuters. Thomson Reuters, 09 June Web. 02 Apr
"Canagliflozin Provided Substantial and Sustained Glycemic Improvements as Monotherapy and in Add-On Combinations in Adults with Type 2 Diabetes in Five Phase 3 Studies." Johnson & Johnson. Jansen Research & Development, 09 June Web. 02 Apr
Clarke, Toni. "FDA Approves Johnson & Johnson Diabetes Drug, Canagliflozin." Reuters. Thomson Reuters, 29 Mar Web. 01 Apr
"Diabetes Treatment, Part 2: Oral Agents for Glycemic Management." Clinical Diabetes. N.p., Oct Web. 12 Apr
FDA Approves Invokana to Treat Type 2 Diabetes. N.p., n.d. Web. 01 Apr. 2013
"Invokana." INVOKANA™ (Canagliflozin) Treatment for Type 2 Diabetes. N.p., n.d. Web. 12 Apr. 2013
Nainggolan, Lisa. "FDA Approves Canagliflozin, a First-in-Class Diabetes Drug." Medscape Log In. N.p., 29 Mar Web. 01 Apr