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What is the primary mechanism of action of SGLT-2 inhibitors?
Where do SGLT-2 inhibitors primarily act to reduce glucose reabsorption?
What is the target of SGLT-2 inhibitors in the kidneys?
What is the effect of SGLT-2 inhibitors on filtered glucose in the kidneys?
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What is the overall effect of SGLT-2 inhibitors on glucose levels?
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What is the effect of canagliflozin on glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) levels?
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Canagliflozin is approved for the treatment of type 1 diabetes.
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What is the potential benefit of canagliflozin on kidney disease?
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Canagliflozin may reduce the risk of _______________ in patients with type 2 diabetes and established cardiovascular disease.
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What is a common adverse reaction of canagliflozin?
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Canagliflozin can cause hypotension in patients with underlying kidney disease.
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Match the following benefits of canagliflozin with their corresponding effects:
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What is a potential risk of canagliflozin in older adults?
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What is the recommended use of dapagliflozin in patients with type 2 diabetes?
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What is a common side effect of dapagliflozin?
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What is a serious side effect of dapagliflozin?
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What is a rare but serious side effect of dapagliflozin?
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In which patients is dapagliflozin particularly contraindicated?
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What is a potential complication of dapagliflozin in patients with a history of osteoporosis?
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Dapagliflozin is indicated for the treatment of which of the following conditions?
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Which of the following is a common side effect of dapagliflozin?
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What is a serious side effect of dapagliflozin?
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In which patients is dapagliflozin particularly contraindicated?
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What is a potential complication of dapagliflozin in patients with a history of osteoporosis?
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In the EMPA-REG OUTCOME trial, what was the reduction in the risk of incident or worsening nephropathy with empagliflozin compared to placebo?
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In the EMPEROR-Reduced trial, what was the reduction in the risk of cardiovascular death or heart failure hospitalization with empagliflozin compared to placebo?
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What was the reduction in the risk of major adverse cardiovascular events (MACE) with empagliflozin in the EMPA-REG OUTCOME trial?
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What was the reduction in the risk of cardiovascular death with empagliflozin in the EMPA-REG OUTCOME trial?
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What was the reduction in the risk of hospitalization for heart failure with empagliflozin in the EMPA-REG OUTCOME trial?
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In the EMPEROR-Reduced trial, what was the improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores with empagliflozin?
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Study Notes
Mechanism of Action
- Canagliflozin inhibits SGLT2 in the kidneys, reducing glucose reabsorption and increasing glucose excretion in urine
- Inhibits glucose reabsorption in the proximal tubule, increasing urinary glucose excretion and reducing glucose reabsorption
- Increases GLP-1 and PYY levels, improving beta-cell function and insulin sensitivity
Type 2 Diabetes Management
- Approved for treatment of type 2 diabetes as monotherapy or with other antidiabetic agents
- Reduces HbA1c levels, fasting plasma glucose, and body weight
- Suitable for patients with inadequate glycemic control on diet and exercise, or with metformin, sulfonylureas, pioglitazone, or insulin
- Can be used in patients with established cardiovascular disease or at high risk of cardiovascular disease
Renal Effects
- Increases urinary glucose excretion, leading to osmotic diuresis and increased urine volume
- May cause acute kidney injury due to dehydration and hypovolemia, particularly in patients with pre-existing kidney disease
- Reduces albuminuria and slows progression of kidney disease in patients with diabetic nephropathy
Cardiovascular Benefits
- Reduces major adverse cardiovascular events (MACE) in patients with type 2 diabetes and established cardiovascular disease
- Reduces hospitalization for heart failure and cardiovascular death
- May reduce blood pressure and improve cardiovascular outcomes in patients with type 2 diabetes
Adverse Reactions
- Common adverse reactions include vulvovaginal candidiasis, balanitis, and urinary tract infections
- Increases risk of amputations, particularly of the toe or midfoot
- May cause hypotension, particularly in patients taking diuretics or with underlying kidney disease
- May increase risk of bone fracture, particularly in older adults
Dapagliflozin (Farxiga)
Indications
- Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- Recommended as a first-line treatment for patients with type 2 diabetes and established cardiovascular disease or at risk of cardiovascular disease
- Can be used as a monotherapy or in combination with other antidiabetic medications, including metformin, sulfonylureas, and insulin
Side Effects
Common Side Effects
- Urinary tract infections
- Female genital mycotic infections (e.g., vaginal yeast infections)
- Increased urination
- Thirst
- Constipation
- Nausea and vomiting
Serious Side Effects
- Dehydration
- Hypotension (low blood pressure)
- Ketoacidosis (a serious metabolic complication)
- Fournier's gangrene (a rare but serious infection of the genital area)
- Increased risk of amputations (particularly in patients with a history of prior amputation)
- Bone fractures (particularly in patients with a history of osteoporosis)
Rare but Serious Side Effects
- Angioedema (a severe allergic reaction)
- Bullous pemphigoid (a serious skin condition)
- Anaphylaxis (a severe, life-threatening allergic reaction)
SGLT-2 Inhibitors
- Inhibit sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules to reduce reabsorption of filtered glucose
Mechanism of Action
- Inhibit glucose reabsorption in the kidneys, increasing glucose excretion in urine
- Reduce glucose reabsorption in the proximal tubule, reducing glucose reabsorption and increasing urinary glucose excretion
- Increase glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) levels, improving beta-cell function and insulin sensitivity
Type 2 Diabetes Management
- Approved for treatment of type 2 diabetes as monotherapy or in combination with other antidiabetic agents
- Reduce HbA1c levels, fasting plasma glucose, and body weight
- Can be used in patients with inadequate glycemic control on diet and exercise, or with metformin, sulfonylureas, pioglitazone, or insulin
- May be used in patients with established cardiovascular disease or at high risk of cardiovascular disease
Renal Effects
- Increase urinary glucose excretion, leading to osmotic diuresis and increased urine volume
- May cause acute kidney injury due to dehydration and hypovolemia, particularly in patients with pre-existing kidney disease
- Can reduce albuminuria and slow progression of kidney disease in patients with diabetic nephropathy
Cardiovascular Benefits
- Reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes and established cardiovascular disease or at high risk of cardiovascular disease
- Reduce hospitalization for heart failure and cardiovascular death
- May reduce blood pressure and improve cardiovascular outcomes in patients with type 2 diabetes
Adverse Reactions
- Common adverse reactions: vulvovaginal candidiasis, balanitis, and urinary tract infections
- Increase risk of amputations, particularly of the toe or midfoot
- May cause hypotension, particularly in patients taking diuretics or with underlying kidney disease
- May increase risk of bone fracture, particularly in older adults
Dapagliflozin (Farxiga)
- Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- Recommended as a first-line treatment for patients with type 2 diabetes and established cardiovascular disease or at risk of cardiovascular disease
- Can be used as a monotherapy or in combination with other antidiabetic medications, including metformin, sulfonylureas, and insulin
Side Effects of Dapagliflozin
- Common side effects: urinary tract infections, female genital mycotic infections, increased urination, thirst, constipation, nausea, and vomiting
- Serious side effects: dehydration, hypotension, ketoacidosis, Fournier's gangrene, increased risk of amputations, bone fractures
- Rare but serious side effects: angioedema, bullous pemphigoid, anaphylaxis
Empagliflozin and Type 2 Diabetes
Diabetic Nephropathy
- Slows kidney disease progression in patients with type 2 diabetes.
- Reduces the risk of incident or worsening nephropathy by 39% compared to placebo.
- Reduces the risk of progression to macroalbuminuria by 38%.
Heart Failure With Reduced Ejection Fraction
- Reduces the risk of heart failure hospitalization in patients with type 2 diabetes.
- Reduces the risk of cardiovascular death or heart failure hospitalization by 25% compared to placebo.
- Improves Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, indicating improved health status and quality of life.
Cardiovascular Outcomes
- Reduces the risk of major adverse cardiovascular events (MACE) by 14% compared to placebo.
- Reduces the risk of cardiovascular death by 38%.
- Reduces the risk of hospitalization for heart failure by 35%.
- Reduces the risk of cardiovascular events in patients with established cardiovascular disease or multiple cardiovascular risk factors.
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Description
This quiz covers the mechanism of SGLT-2 inhibitors, which reduce glucose reabsorption in the kidneys, and their role in diabetes treatment. Learn about their effects on glucose levels and kidney function.
