Sodium glucose co transporter Inhibitors- the latest addition in glycemic Management

1. SODIUM–GLUCOSE CO-TRANSPORTERS
(SGLTS) INHIBITORS
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2. INTRODUCTION
• T2DM progressive β-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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3. MOA OF OHAS
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4. HISTORY
• Phlorizin, a bitter 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.
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5. Familial Renal Glycosuria
• A rare 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.
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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 SGLT2 INHIBITORS DIFFERENT FROM OTHER
ANTI-HYPERGLYCEMIC AGENTS?
• Non-insulin dependent mechanism
• SGLT2 inhibitors can be used in early or late
type 2 diabetes
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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
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12. CANAGLIFLOZIN (INVOKANA)™
• Reduces glucose absorption 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. DAPAGLIFLOZIN (FARXIGA)
• Improves glycemic control 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
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16. “An increased number of bladder cancers were diagnosed among Farxiga
users in clinical trials so Farxiga is not recommended for patients with active
bladder cancer. ”
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17. • Dose:- Initial: 5 mg 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. 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
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21. • C/I in renal impairement
• No hepatic impairement
• No drug interactions with CVS drugs like verapamil,
ramipril, digoxin, and anticoagulant warfarin.
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23. Advantages Vs. Disadvantages
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24. CONCLUSIONS
• SGLT2 inhibitors are 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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