Dapagliflozin is a selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity. Dapagliflozin selectively and potently inhibits SGLT2 compared to SGLT1, which is the cotransporter of glucose in the gut. Dapagliflozin is a Sodium-Glucose Cotransporter 2 Inhibitor. The mechanism of action of dapagliflozin is as a Sodium-Glucose Transporter 2 Inhibitor.
Dapagliflozin is indicated for the management of diabetes mellitus type 2, and functions to improve glycemic control in adults when combined with diet and exercise. Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor, which prevents glucose reabsorption in the kidney. Using dapagliflozin leads to heavy glycosuria (glucose excretion in the urine), which can lead to weight loss and tiredness. Dapagliflozin was approved by the FDA on Jan 08, 2014. Dapagliflozin is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Mechanism of Action of Dapagliflozin
Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2) which are responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter mechanism causes blood glucose to be eliminated through the urine. In clinical trials, dapagliflozin lowered HbA1c by 0.6 versus placebo percentage points when added to metformin.
Dapagliflozin is a selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity. Dapagliflozin selectively and potently inhibits SGLT2 compared to SGLT1, which is the cotransporter of glucose in the gut.
Indications of Dapagliflozin
- Type 2 Diabetes Mellitus
- Management of glycemic control in patients with type 2 diabetes mellitus, in combination with diet and exercise.
- Dapagliflozin is indicated for adjunct management of glycemic control in patients with type 2 diabetes mellitus, in combination with diet and exercise.
- indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control as:MonotherapyWhen diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance.Add on combination therapyIn combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control
Contra-Indications of Dapagliflozin
- Infection
- Low blood sugar
- Pituitary hormone deficiency
- Decreased function of the adrenal gland
- Inadequate vitamin B12
- Excess body acid
- Extreme loss of body water
- Habit of drinking too much alcohol
- Alcohol intoxication
- Heart attack
- Suddenly serious symptoms of heart failure
- Liver problems
- Recent operation
- Fever
- Shock
- Severe vomiting
- Severe diarrhea
- Serious lack of oxygen in the blood
- Weakened patient
- Injury
- Sepsis syndrome
- X-Ray Study with intravenous iodine contrast agent
- Kidney disease with likely reduction in kidney function
- Acute inflammation of the pancreas
- Chronic inflammation of the pancreas
- Moderate to Severe kidney impairment
Dosage of Dapagliflozin
Strengths: 5 mg; 10 mg
Diabetes Type 2
- Initial dose: 5 mg orally once a day
- May increase to 10 mg orally once a day in patients tolerating therapy with a lower dose and requiring additional glycemic control
- Maximum dose: 10 mg/days
Side Effects of Dapagliflozin
Most common
- Abdominal or stomach discomfort
- increased urination.
- low blood pressure,
- difficult, burning, or painful urination
- discharge with a strong odor from the penis
- increased potassium blood levels (hyperkalemia),
- low blood sugar (hypoglycemia), and
- diarrhea
- gas (flatulence)
- symptoms of weakness, muscle pain (myalgia)
- upper respiratory tract infection
- low blood sugar (hypoglycemia)
- abdominal pain (GI complaints), lactic acidosis (rare)
- low blood levels of vitamin B-12
- nausea,vomiting
- chest discomfort
- chills, dizziness
- bloating/abdominal distention
- constipation
- heartburn
More common
- Fever
- muscle aches
- sore throat
- Abdominal or stomach discomfort
- cough or hoarseness
- decreased appetite
- diarrhea
- fast or shallow breathing
- fever or chills
- general feeling of discomfort
- lower back or side pain
- muscle pain or cramping
- painful or difficult urination
Less common
- Back pain
- difficulty having a bowel movement (stool)
- pain in the arms or legs
- Abnormal stools
- bad, unusual, or unpleasant (after) taste
- change in taste
- difficulty with moving
- discoloration of the fingernails or toenails
- flu-like symptoms
- joint pain
- rash
- a runny nose
- sneezing
- stuffy nose
- swollen joints
Drug Interactions of Dapagliflozin
Dapagliflozin may interact with following drugs, supplements & may decrease the efficacy of the drug
- androgens (e.g., methyltestosterone, nandrolone, testosterone)
- angiotensin-converting enzyme inhibitors (ACEIs; captopril, ramipril)
- angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
- angiotensin-converting enzyme inhibitors (ACEIs; captopril, enalapril,ramipril)
- antipsychotic medications (e.g., chlorpromazine, haloperidol, olanzapine,
- birth control pills
- bupropion
- atorvastatin
- atypical antipsychotics (e.g., aripiprazole, clozapine, olanzapine; quetiapine, risperidone)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- barbiturates (e.g., pentobarbital, phenobarbital)
- crizotinib
- cyclosporine
- cyproterone
- dabrafenib
- corticosteroids (e.g., dexamethasone, prednisone)
- diabetic drugs (e.g., glyburide, insulin, repaglinide, sitagliptin)
- digoxin
- diuretics (e.g., furosemide, hydrochlorothiazide)
- HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
- iodinated contrast material
- phenytoin
- quinolone antibiotics (e.g., levofloxacin, moxifloxacin)
- selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, sertraline paroxetine,
- trimethoprim
- sulfonamide antibiotics (“sulfas”; e.g., sulfisoxazole, sulfamethoxazole)
- somatotropin
- sulfamethoxazole
- testosterone
- verapamil
Pregnancy & Lactation of Dapagliflozin
FDA Pregnancy Category C
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
This medication should not be used while breast-feeding.
References
