Canagliflozin Side Effects

Medically reviewed by Philip Thornton, DipPharm. Last updated on Apr 1, 2025.

Applies to canagliflozin: oral tablet.

Precautions

It is very important that your doctor check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine during the second and third part of your pregnancy can harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine may increase your risk of having leg, toe, or midfoot amputation (leg removal surgery). Check with your doctor right away if you have pain, tenderness, sores or ulcers, or infections on your leg or foot.

Dizziness, lightheadedness, or fainting may occur with this medicine. This is more common if you have kidney disease, low blood pressure, or if you are taking a diuretic (water pill). Taking plenty of fluids each day may help. Drink plenty of water during exercise or in hot weather. Check with your doctor if you have severe nausea, vomiting, or diarrhea that does not stop. This may cause you to lose too much water.

Ketoacidosis (high ketones and acid in the blood) may occur while you are using this medicine. This can be life-threatening and requires immediate medical attention. Your doctor may give you insulin, fluid, and carbohydrate replacement to treat this condition. Tell your doctor right away if you have nausea, vomiting, trouble breathing, increased thirst or urination.

Check with your doctor right away if you have bloody urine, decrease in how much or how often you urinate, an increase in blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, trouble breathing, unusual tiredness or weakness, vomiting, or weight gain. These could be symptoms of a serious kidney problem.

This medicine may cause vaginal yeast infections in women and yeast infections of the penis in men. This is more common in patients who have a history of genital yeast infections or in men who are not circumcised. Women may have a vaginal discharge, itching, or odor. Men may have redness, itching, swelling, or pain around the penis, or a discharge with a strong odor from the penis. Check with your doctor right away if you have any of these symptoms.

Serious allergic reactions may occur with this medicine. Check with your doctor right away if you have a skin rash, hives or welts, itching, redness of the skin, trouble breathing, or large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals.

This medicine may increase the risk of bone fractures. Ask your doctor about ways to keep your bones strong to help prevent fractures.

This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with other diabetes medicines (eg, insulin, glipizide, or glyburide). Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Talk to your doctor about the best way to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your diabetes medicine, overeat or do not follow your diet plan, have a fever or infection, or do not exercise as much as usual. Some symptoms of high blood sugar include blurred vision, drowsiness, dry mouth, flushed and dry skin, a fruit-like breath odor, increased frequency and amount of urination, ketones in the urine, loss of appetite, nausea or vomiting, rapid and deep breathing, tiredness, or unusual thirst. If symptoms of high blood sugar occur, check your blood sugar level and call your doctor for instructions.

This medicine may increase risk of having urinary tract infections, including pyelonephritis or urosepsis. Check with your doctor right away if you have bladder pain, bloody or cloudy urine, difficult, burning, or painful urination, or lower back or side pain.

This medicine may cause a rare but serious bacterial infection, called necrotizing fasciitis of the perineum or Fournier's gangrene, which can cause damage to the tissue under the skin in the area between and around the anus and genitals (perineum). Fournier's gangrene may lead to hospitalization, multiple surgeries, or death. Check with your doctor right away if you have fever, unusual tiredness or weakness, or pain, tenderness, redness, or swelling of the area between and around your anus and genitals.

This medicine may cause serious allergic reactions, including anaphylaxis or angioedema. These reactions can be life-threatening and require immediate medical attention. Call your doctor right away if you have a rash, itching, blistering, peeling, or loosening of the skin, fever or chills, trouble breathing or swallowing, or any swelling of your hands, face, mouth, or throat while you are using this medicine.

Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain medical tests (eg, urine glucose tests may not be accurate). Also, you may need to Stop taking canagliflozin at least 3 days before you have surgery.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Serious side effects of canagliflozin

Along with its needed effects, canagliflozin 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 canagliflozin:

Other side effects of canagliflozin

Some side effects of canagliflozin 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:

For healthcare professionals

Applies to canagliflozin: oral tablet.

General adverse events

The most commonly reported adverse reactions have included female genital mycotic infections, urinary tract infection, and increased urinary frequency.^[Ref]

Musculoskeletal

• Common (1% to 10%): Lower limb amputations
• Uncommon (0.1% to 1%): Bone fracture, upper extremity fracture
• Frequency not reported: Loss of bone mineral density at hip and lower spine^[Ref]

In the CANVAS trial, amputations per 1000 patients per year in patients receiving canagliflozin (100 mg or 300 mg per day) were 5.8 compared to 2.8 amputations per 1000 patients per year in the placebo group. In the CANVAS-R trials, these numbers were 7.5 and 4.2, respectively. The total number of amputations among canagliflozin-treated patients (n=5790) was 221 compared with 69 in the placebo group (n=4344). Amputations of the toe and midfoot were the most frequent; however, amputations involving the leg, below and above the knee, also occurred.

On September 10, 2015, the US Food and Drug Administration issued a drug safety communication regarding new information on bone fracture risk and decreased bone mineral density with use of canagliflozin. Based on updated data, fractures have occurred as early as 12 weeks after starting therapy with trauma that is usually minor, such as falling from standing height. Additionally, a 2-year study (n=714) has shown a greater loss of bone mineral density at the hip and lower spine in canagliflozin treated patients compared with placebo.^[Ref]

Genitourinary

• Very common (10% or more): Female genital mycotic infections including vulvovaginal mycotic infection, vulvovaginitis, vaginal infection, vulvitis, and genital infection fungal (up to 11.4%), recurrent male genital mycotic infections (22%)
• Common (1% to 10%): Urinary tract infection, increased urination, male genital mycotic infections including balanitis, balanoposthitis, balanitis candida, and fungal genital infection
• Uncommon (0.1% to 1%): Phimosis
• Postmarketing reports: Urosepsis, pyelonephritis, Fournier's gangrene^[Ref]

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 men and women (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). All SGLT2 inhibitor drugs except ertugliflozin were included in the reports. Ertugliflozin being the most recently approved agent, is expected to have the same risk, but insufficient patient use to assess risk. All patients were hospitalized, all required surgery, all required surgical debridement, 5 required more than 1 surgery and 1 required skin grafting. Four cases were complicated by diabetic ketoacidosis, acute kidney injury, and septic shock, leading to prolonged hospitalization, and death in 1 case. In the general population, Fournier's gangrene occurs in about 1.6 out of 100,000 males annually, with the highest incidence in men 50 to 79 years. Since diabetes is a risk factor for Fournier's gangrene, a review of the FAERS database for the last 34 years was done and only 6 cases (all males, median age 57 years) were found with several other classes of antidiabetic drugs. Findings with SGLT2 inhibitors appear to show an association over a shorter time frame and involve both males and females.^[Ref]

Cardiovascular

• Common (1% to 10%): Adverse reactions related to reduced intravascular volume (postural hypotension, orthostatic hypotension, hypotension, dehydration, and syncope)^[Ref]

Metabolic

• Very common (10% or more): Hypoglycemia when combined with insulin or an insulin secretagogue (up to 49%), hyperkalemia (up to 27%)
• Common (1% to 10%): Increased serum magnesium, increased serum phosphate, increased low-density lipoprotein (LDL-C)
• Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis^[Ref]

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]

Gastrointestinal

• Common (1% to 10%): Constipation, thirst, nausea, abdominal pain, pancreatitis^[Ref]

Hypersensitivity

• Common (1% to 10%): Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema
• Frequency not reported: Serious hypersensitivity reaction
• Postmarketing reports: Anaphylaxis^[Ref]

Renal

• Frequency not reported: Increases in serum creatinine, decreases in eGFR, renal impairment, acute renal failure
• Postmarketing reports: Acute kidney injury^[Ref]

In a pooled analysis among patients with moderate renal impairment, the incidence of renal related adverse reactions such as increased serum creatinine, decreased eGFR, renal impairment, or acute renal failure, was 8.9% and 9.3% in patients receiving canagliflozin 100 mg or 300 mg, compared with 3.7% in those receiving comparator drug or placebo.

From March 2013 to October 2015, the US FDA received 101 confirmable case reports of acute kidney injury (AKI) with use of canagliflozin (n=73) or dapagliflozin (n=28). Hospitalization was necessary for evaluation and management in 96 cases; admission to the intensive care unit occurred in 22 cases, and death occurred in 4 patients, of which 2 were cardiac-related. Dialysis was necessary in 15 patients, 3 of whom had a history of chronic kidney disease or previous AKI. In 58 cases, time to onset of AKI was within 1 month or less of initiating therapy. In 78 cases in which drug discontinuation was reported, 56 reported subsequent improvement; 3 patients recovered with sequelae, 11 patients did not recover (including the 4 deaths mentioned earlier). Median age was 57 years (range 28 to 78 years; based on 84 cases reporting age). Concomitant ACE inhibitor therapy was reported in 51 cases, diuretic use in 26 cases, and NSAID use in 6 cases. Almost half the patients reported a change in renal function at time of diagnosis (median elevation of serum creatinine from baseline 1.6 mg/dL [based on 32 cases reporting serum creatinine] and median decrease in eGFR 46 mL/min/1.73m2 [based on 13 cases reporting eGFR]).^[Ref]

Oncologic

• Uncommon (0.1% to 1%): Renal cell carcinoma

In the CANVAS trial (mean duration of follow-up of 5.7 years), the incidence of renal cell carcinoma was 0.29% (8/2716) in patients receiving this drug (placebo: 0.15% [2/1331]) excluding patients with less than 6 months of follow-up, less than 90 days of treatment, or a history of renal cell carcinoma.

Dermatologic

• Uncommon (0.1% to 1%): Photosensitivity reactions, rash, urticaria^[Ref]

Other

• Common (1% to 10%): Fatigue, asthenia, falls
• Uncommon (0.1% to 1%): Leg and foot amputations^[Ref]

Final results from 2 clinical trials, the CANVAS (Canagliflozin Cardiovascular Assessment Study) and the CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) have shown leg and foot amputations occurred almost twice as often in canagliflozin treated patients compared with placebo treated patients. Amputations of the toe and middle of the foot were most common, however some amputations involved the leg, below and above the knee. Some patients had more than 1 amputation; some involved both limbs.

The risk of amputation calculated from the CANVAS trial showed 5.9 per 1000 patients per year for canagliflozin treated patients compared to 2.8 per 1000 patients per year for placebo patients. The CANVAS-R trial showed 7.5 per 1000 patients per year compared to 4.2 per 1000 patients per year for canagliflozin treated patients and placebo patients, respectively.^[Ref]

See also:

Frequently asked questions

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Further information

Canagliflozin side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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