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SGLT-2 Inhibitors

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. SGLT-1 and SGLT-2.

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SGLT-2 Inhibitors

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  1. 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 50-80 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 InhibitorFirst In Class

  7. Canagliflozin Side Effects http://www.invokanahcp.com/safety-information/safety-and-tolerability-profile?utm_source=google&utm_medium=cpc&utm_campaign=Invokana+HCP&utm_term=canagliflozin%20side%20effects&utm_content=Side+Effects+-+Exact|mkwid|suZUJen2m|pcrid|24016786155

  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

  12. References • Berkrot, Bill. "Johnson & Johnson Diabetes Drug Tops Older Therapies in Studies." Reuters. Thomson Reuters, 09 June 2012. Web. 02 Apr. 2013. • "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 2012. Web. 02 Apr. 2013. • Clarke, Toni. "FDA Approves Johnson & Johnson Diabetes Drug, Canagliflozin." Reuters. Thomson Reuters, 29 Mar. 2013. Web. 01 Apr. 2013. • "Diabetes Treatment, Part 2: Oral Agents for Glycemic Management." Clinical Diabetes. N.p., Oct. 2007. Web. 12 Apr. 2013. • 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. 2013. Web. 01 Apr. 2013.

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