ERLI_Product Presentation_without Video.pptx

Empagliflozin 10 mg,25 mg

1. Dr. Masood Jawaid Director Medical Affairs & Pharmacy Services

2. Table of Content Anatomy of kidney Functions of kidney Anatomy of nephron Mechanism of glucose reabsorption SGLT2is Mechanism of Action of SGLT2is Diabetes Associated Ventricular Remodeling Diabetes Associated Reno-Vascular Changes Indication, Usage, Dosage, Administration, Use in Specific Population, Contraindication, Adverse Events, Drug Reactions Guidelines Clinical Trials

3. Anatomy of Kidney The kidneys are at the back of the abdominal cavity, with one sitting on each side of the spine. The right kidney is generally slightly smaller and lower than the left, to make space for the liver. Each kidney weighs 125–170 grams (g) in males and 115–155 g in females. A tough, fibrous renal capsule surrounds each kidney. Beyond that, two layers of fat serve as protection. The adrenal glands lay on top of the kidneys. Inside the kidneys are a number of pyramid-shaped lobes. Each consists of an outer renal cortex and an inner renal medulla. Nephrons flow between these sections. These are the urine-producing structures of the kidneys.

4. Anatomy of Kidney

5. Functions of Kidney Maintaining overall fluid balance. Regulating and filtering minerals from blood. Filtering waste materials from food, medications, and toxic substances. Creating hormones that help produce red blood cells, promote bone health, and regulate blood pressure.

6. Anatomy of Nephron

7. Glucose Reabsorption – Normoglycemia

8. Glucose Reabsorption – Hyperglycemia

9. Mechanism of Glucose Reabsorption

10. Glucose Reabsorption – Cellular level

11. Sodium Glucose cotransporter - 2 (SGLT2) Inhibitors

12. MECHANISM OF ACTION-SGLT2

13. MECHANISM OF ACTION-SGLT2

14. MECHANISM OF ACTION-SGLT2

15. Globally Available SGLT2is Canagliflozin ( Invokana ) Dapagliflozin ( Forxiga ) Empagliflozin (Jardiance) Ertugliflozin ( Steglatro )

16. Globally Available SGLT2is Ertugliflozin 2018 5 mg QD eGFR≥60 mL/min/1.73m 2

17. Diabetes Associated Ventricular Remodeling

18. Diabetes Associated Reno-Vascular Changes

19. GFR changes in diabetes and putative mechanism of renal benefit with SGLT2 Inhibitors

20. Indication & Usage Empagliflozin ( ERLI ) is indicated: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease Limitation of Use: Empagliflozin ( ERLI ) is not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis

21. Dosage & Administration The recommended dose of Empagliflozin ( ERLI )is 10 mg once daily in the morning, taken with or without food. In patients tolerating Empagliflozin ( ERLI ), the dose may be increased to 25 mg once daily In patients with volume depletion, correcting this condition prior to initiation of Empagliflozin ( ERLI ) is recommended

22. Patients with Renal Impairment Assessment of renal function is recommended prior to initiation of Empagliflozin ( ERLI ) and periodically thereafter . No dose adjustment is needed in patients with an eGFR greater than or equal to 45 mL/min/1.73 m2 Empagliflozin ( ERLI ) should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m2. Empagliflozin ( ERLI ) should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m2

23. Contraindications History of serious hypersensitivity reaction to empagliflozin or any of the excipients in ( ERLI ) Severe renal impairment, end-stage renal disease, or dialysis

24. ADVERSE REACTIONS Hypotension Ketoacidosis Acute Kidney Injury and Impairment in Renal Function Urosepsis and Pyelonephritis Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Genital Mycotic Infections Increased Low-Density Lipoprotein Cholesterol (LDL-C)

25. Drug Interactions Co administration of Empagliflozin with: Diuretics: Resulted in increased urine volume and frequency. Insulin or Insulin Secretagogues : Increases the risk for hypoglycemia Amlodipine: May potentiate the hypotensive Propranolol: May confusion, dizziness, faster heart beat, tremors (shaking) and increased sweating. Dexamethasone: cases of high blood sugar levels have been seen in some patients.

26. Use in Specific Populations

27. Use in Specific Populations

28. Pharmacokinetics Absorption: peak plasma concentrations of empagliflozin were reached at 1.5 hours post-dose . Distribution: Plasma Protein Binding is 86.2% Elimination: Half Life is 12.4 Hours Excrete 54.4% through urine & 41.2% through feces

29. Guidelines

30. AACE – Glycemic Control Algorithm 2019

31. ADA - Guidelines

32. Choosing glucose lowering agent in those with ASCVD or CKD

33. Choosing glucose lowering agents to promote weight loss

34. Choosing glucose lowering agents to minimize hypoglycemia

35. Considering Oral Therapy in Combination with Injectable Therapies

36. Clinical Trials

37. Empagliflozin versus dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin , glimepiride and DPPIVi: A 52-week prospective observational study Method: A n open- labeled , prospective, 52-week study conducted in T2D patients with HbA1c ranging 7.5–12.0% with metformin, glimepiride and dipeptidyl peptidase-4 inhibitors n = 350 Empa = 176 Dape = 174

38. Slope of change in HbA1c from baseline with Empagliflozin compared with sitagliptin or glimepiride in patients with type 2 diabetes Method: Double-blind, active-controlled trial Metformin (immediate release, IR)- treated patients with type 2 diabetes Randomized to receive Empagliflozin 25 mg/d or glimepiride 1-4 mg/d as add-on to metformin for 104 weeks n = 1,545 Empa = 765 Dape = 780

39. EMPA-REG OUTCOME Method: A total of 7020 patients were treated (median observation time, 3.1 years ). Randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily

40. EMPA-REG OUTCOME Method: A total of 7020 patients were treated (median observation time, 3.1 years ). Randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily