Summary

Commonly reported side effects of dapagliflozin/metformin include: lactic acidosis. Other side effects include: cystitis, pyelonephritis, urinary tract infection, vulvovaginal candidiasis, bacterial vaginosis, genital candidiasis, genitourinary infection, nasopharyngitis, prostatitis, urethritis, vaginal infection, vulvitis, vulvovaginitis, nausea, and vomiting. Continue reading for a comprehensive list of adverse effects.

Applies to dapagliflozin / metformin: oral tablet extended release.

Serious side effects

Along with its needed effects, dapagliflozin/metformin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking dapagliflozin / metformin:

More common

• Bladder pain
• bloody or cloudy urine
• change in the color, amount, or odor of vaginal discharge
• difficult, burning, or painful urination
• frequent urge to urinate
• lower back or side pain

Rare

• Decreased appetite
• diarrhea
• fast, shallow breathing
• general feeling of discomfort
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• muscle pain or cramping
• nausea
• sleepiness
• stomach discomfort
• unusual tiredness or weakness

Incidence not known

• Anxiety
• blurred vision
• chest tightness
• chills
• clay-colored stools
• cold sweats
• confusion
• cool, pale skin
• dark urine
• depression
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast heartbeat
• fever
• headache
• hives, itching, or rash
• hoarseness
• increased hunger
• irritation
• joint pain, stiffness, or swelling
• loss of appetite
• loss of consciousness
• nightmares
• pain, tenderness, redness, or swelling of the area between the anus and genitals
• redness of the skin
• seizures
• shakiness
• slurred speech
• sweating
• swelling of the eyelids, face, lips, hands, or feet
• trouble swallowing
• unpleasant breath odor
• vomiting of blood
• yellow eyes or skin

Other side effects

Some side effects of dapagliflozin / metformin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Muscle aches
• sore throat
• stuffy or runny nose

Less common

• Back pain
• body aches or pain
• difficulty having a bowel movement
• tender, swollen glands in the neck
• voice changes

For Healthcare Professionals

Applies to dapagliflozin / metformin: oral tablet extended release.

General

The most common adverse reactions reported with this combination drug included female genital mycotic infection, nasopharyngitis, urinary tract infection, diarrhea, and headache.^[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Volume depletion (Including dehydration, hypovolemia, orthostatic hypotension, or hypotension)^[Ref]

Dermatologic

Dapagliflozin:

Postmarketing reports: Rash

Metformin:

Uncommon (0.1% to 1%): Angioedema

Very rare (less than 0.01%): Urticaria, erythema, pruritus^[Ref]

Endocrine

Dapagliflozin:

Frequency not reported: Small Increase in serum parathyroid hormone levels^[Ref]

-Small increases in serum parathyroid hormone (PTH) levels were observed with increases larger in subjects with higher baseline PTH concentrations.^[Ref]

Gastrointestinal

Dapagliflozin-Metformin:

Common (1% to 10%): Diarrhea, nausea, constipation

Dapagliflozin:

Uncommon (0.1% to 1%): Constipation, dry mouth

Metformin:

Very common (10% or more): Nausea, vomiting, diarrhea, abdominal pain, loss of appetite^[Ref]

Genitourinary

Genital mycotic infections have been commonly reported with dapagliflozin treatment. Discontinuation due to genital infection occurred in 0.2% of patients in dapagliflozin clinical trials. Infections were more frequently reported in females than males, and patients with a history of genital mycotic infections were more likely to have an infection than those without a history.

In the 5 years (2013 to 2018) since SGLT2 inhibitor approval, 12 cases of Fournier's gangrene have been reported. Reports were almost equal in adults (men=7; women=5), ages ranged from 38 to 78 years, and the average time to onset after starting an SGLT2 inhibitor was 9.2 months (range 7 days to 25 months).^[Ref]

Common (1% to 10%): Escherichia urinary tract infection, female genital mycotic infections (including vulvovaginal mycotic infection, vaginal infection, genital infection, vulvovaginitis, fungal genital infection, vulvovaginal candidiasis, vulval abscess, vulvitis, genital candidiasis, and vaginitis bacterial), urinary tract infections (including urinary tract infection, cystitis, pyelonephritis, urethritis, and prostatitis), male genital mycotic infections (including balanitis, fungal genital infection, penile infection, trigonitis, balanitis candida, genital candidiasis, balanoposthitis, balanoposthitis infective, genital infection, posthitis), nocturia (including pollakiuria, polyuria, and increased urine output), discomfort with urination

Uncommon (0.1% to 1%): Vulvovaginal pruritus

Postmarketing reports: Fournier's gangrene, urosepsis, pyelonephritis^[Ref]

Hematologic

Dapagliflozin:

Common (1% to 10): Increased hematocrit

Metformin:

Very rare (less than 0.01%): Decreased vitamin B12 serum levels^[Ref]

Hepatic

Metformin:

Very rare (less than 0.01%): Liver function disorders, liver function tests abnormalities, hepatitis

Postmarketing reports: Cholestatic, hepatocellular, mixed hepatocellular liver injury^[Ref]

Hypersensitivity

Dapagliflozin:

Uncommon (0.1% to 1%): Serious anaphylactic reactions, severe cutaneous reactions

Frequency not reported: Hypersensitivity reactions (included urticaria, hypersensitivity)^[Ref]

Immunologic

Common (1% to 10): Influenza^[Ref]

Metabolic

Hypoglycemia was reported more frequently when this drug was added to sulfonylurea or insulin (up to 43%).

Twenty reports of acidosis have been identified in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database during the period March 2013 through 06 June 2014. All patients required emergency room treatment or hospitalization. These cases were not typical of ketoacidosis or diabetic ketoacidosis (DKA) in that they occurred in patients with type 2 diabetes and their blood sugar levels were only slightly increased. Some factors identified as potentially triggering the acidosis included major illness, reduced food and fluid intake, and reduced insulin dose.^[Ref]

Dapagliflozin-Metformin:

Very common (10% or more): Hypoglycemia (when used with sulfonylurea or insulin)

Common (1% to 10%): Dyslipidemia

Dapagliflozin:

Common (1% to 10%): Hyperphosphatemia, increases in low-density lipoprotein cholesterol (LDL-C)

Uncommon (0.1% to 1%): Decreased weight, thirst

Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis

Metformin:

Very rare (less than 0.01%): Lactic acidosis, vitamin B12 deficiency^[Ref]

Musculoskeletal

Dapagliflozin-Metformin:

Common (1% to 10%): Back pain

Dapagliflozin:

Common (1% to 10%): Pain in extremity^[Ref]

Nervous system

Dapagliflozin-Metformin:

Common (1% to 10%): Headache, dizziness

Metformin:

Common (1% to 10%): Taste disturbance^[Ref]

Oncologic

Dapagliflozin:

Uncommon (0.1% to 1%): Bladder cancer^[Ref]

Newly diagnosed bladder cancer was reported in 10 of 6045 (0.17%) patients receiving dapagliflozin in clinical trials.^[Ref]

Other

Uncommon (0.1% to 1%): Fungal infection

Renal

Cases of acute kidney injury have been reported during the postmarketing period with dapagliflozin. Some cases required hospitalization and dialysis; some reports were in patients less than 65 years old.^[Ref]

Dapagliflozin:

Uncommon (0.1% to 1%): Increased serum creatinine, increased blood urea

Frequency not reported: Decreases in eGFR, kidney infection

Postmarketing reports: Acute kidney injury and impaired renal function^[Ref]

Respiratory

Common (1% to 10%): Nasopharyngitis, cough, pharyngitis^[Ref]