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sglt2-160421141320 (1) (2).pptx
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- 2. 7/13/201 5 2 INTRODUCTI ON • T2DM progressiveβ-cell dysfunction & peripheral insulin resistance • Persisting hyperglycemia β-cell dysfunction & worsens insulin resistance • T2DM obese, HTN and dyslipidemia • Need arises for new, well tolerated in all stages of disease
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- 4. HISTO RY • Phlorizin, abitter white glycoside isolated from apple tree bark by French chemists in 1835, is a naturally occurring inhibitor of both SGLT1 and SGLT2 and was used for the treatment of diabetes in the pre-insulin era. 7/13/201 5 4
- 5. 7/13/201 5 5 Familial Renal Glycosuria • Arare inherited condition caused by a mutation in the SGLT2 gene. • Patients with this condition have varying degrees of glycosuria • They remain asymptomatic • They do not become dehydrated or become hypoglycemic • They can excrete up to 125 g of glucose/day.
- 6. 7/13/201 5 6 SGLT2- INHIBITORS • Sodium–glucose co-transporters(SGLTs) are the newest drugs • MOA is by blocking the glucose reabsorption in the kidney, inhibitors of the sodium-glucose cotransporter 2 (SGLT2) increase the urinary glucose excretion
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- 10. HOW ARE SGLT2INHIBITORS DIFFERENT FROM OTHER ANTI- HYPERGLYCEMIC AGENTS? • Non-insulin dependent mechanism • SGLT2 inhibitors can be used in early or late type 2 diabetes 7/13/201 5 10
- 11. 7/13/201 5 11 FDA APPROVED SGLT2 INHIBITORS Canagliflozin (INVOKANA)™ • Approved March 2013 Dapagliflozin (FARXIGA)™ • Approved in Europe since 2012 • FDA declined approval in 2012 due to possible cancer signal with drug • FDA recommends approval December 2013 • Approved January 2014 Empagliflozin ( Jardiance ) ™ • Approved in January 2014
- 12. 7/13/201 5 12 CANAGLIFLOZIN (INVOKANA)™ • Reduces glucoseabsorption by 31% in first hour and 20% by next hour of food intake. • Dosage:- : Initial: 100 mg once daily prior to first meal of the day; may increase to 300 mg once daily (only in patients with GFR ≥60 mL/minute/1.73 m2) • Drug interactions :- UGT inducers (e.g., rifampin, phenytoin, phenobarbital, ritonavir) se metabolism of CFZ. • C/I- renal impairement
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- 15. 7/13/201 5 15 DAPAGLIFLOZIN (FARXIGA) • Improves glycemiccontrol in patients with T2DM when used as monotherapy, or when added to metformin, glimepiride or insulin. • Helps in weight reduction • Decrease in systolic blood pressure noted • Less incidence of hypoglycemia • Controversy- higher rate of bladder and breast cancer in the groups treated with dapagliflozin
- 16. “An increased numberof bladder cancers were diagnosed among Farxiga users in clinical trials so Farxiga is not recommended for patients with active bladder cancer. ” 7/13/201 5 16
- 17. 7/13/201 5 17 • Dose:-Initial: 5mg once daily; may increase to 10 mg once daily. • C/I:- renal impairement, bladder cancer • Drug interactions:- may enhance hypoglycemic effects when used with insulin & sulfonylureas
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- 20. 7/13/201 5 20 EMPAGLIFLOZIN ( JARDIANCE )™ • Pharmacokinetic studies of empagliflozin have shown that it is rapidly absorbed following oral administration, reaching maximal plasma concentrations within 1–3 hours. • Once-daily administration of empagliflozin in patients with type 2 diabetes is well tolerated • Dose :- Initial 10 mg once daily; may increase to 25 mg once daily • No risk of hypoglycemia
- 21. 7/13/201 5 21 • C/I inrenal impairement • No hepatic impairement • No drug interactions with CVS drugs like verapamil, ramipril, digoxin, and anticoagulant warfarin.
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- 24. 7/13/201 5 24 CONCLUSIO NS • SGLT2 inhibitorsare a new option in treatment for type 2 diabetes • Insulin independent mechanism of action allows use in early and late stages of diabetes • Weight loss is a desirable side effect • Long term outcome studies are necessary to assess risk of cardiovascular events
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