SGLT-2 Inhibitors in Diabetes Management

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.