Short answer: In four pooled 26-week placebo-controlled canagliflozin trials, most with metformin, the most common side effects were female genital yeast infections (10.6% on 100 mg and 11.6% on 300 mg vs 2.8%), urinary tract infections (5.9% and 4.4% vs 3.8%) and increased urination (5.1% and 4.6% vs 0.7%). Invokamet has a boxed warning for lactic acidosis from its metformin part.
What Invokamet is approved for: Invokamet combines canagliflozin, an SGLT2 inhibitor, with metformin, a biguanide. Along with diet and exercise, Invokamet and Invokamet XR are approved to improve blood sugar control in adults and children 10 years and older with type 2 diabetes (section 1). In adults with type 2 diabetes the canagliflozin part also lowers the risk of major heart events in established heart disease, and of kidney failure, heart death and heart failure hospital stays in diabetic kidney disease with albuminuria above 300 mg/day. It is not recommended for type 1 diabetes.
Source
INVOKAMET (canagliflozin and metformin hydrochloride) tablets and INVOKAMET XR (canagliflozin and metformin hydrochloride extended-release) tablets, for oral use, prescribing information and Medication Guide. Janssen Pharmaceuticals. DailyMed, version published August 25, 2026. DailyMed setid 6868666b-c25e-40d1-9d1f-306bbe9390c1
WARNING: LACTIC ACIDOSIS
Cases of metformin-associated lactic acidosis reported after approval have resulted in death, low body temperature, low blood pressure and slow heart rhythms that resist treatment. It often starts subtly, with only vague symptoms such as feeling unwell, muscle aches, trouble breathing, sleepiness and abdominal pain. It was marked by blood lactate above 5 mmol/L, anion gap acidosis without ketones, a raised lactate to pyruvate ratio, and metformin levels generally above 5 mcg/mL. Risk factors include kidney impairment, certain drugs (for example carbonic anhydrase inhibitors such as topiramate), age 65 or older, a radiology study with contrast, surgery and other procedures, low-oxygen states such as acute heart failure, heavy alcohol use, liver impairment and mitochondrial diseases. If it is suspected, Invokamet is stopped immediately and supportive care is started in a hospital; prompt hemodialysis is recommended.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Invokamet.
| Adverse reaction | Placebo (N=646) | Canagliflozin 100 mg (N=833) | Canagliflozin 300 mg (N=834) |
|---|---|---|---|
| Urinary tract infections | 3.8% | 5.9% | 4.4% |
| Increased urination | 0.7% | 5.1% | 4.6% |
| Thirst | 0.1% | 2.8% | 2.4% |
| Constipation | 0.9% | 1.8% | 2.4% |
| Nausea | 1.6% | 2.1% | 2.3% |
| Female genital mycotic infections (women: N=312, 425, 430) | 2.8% | 10.6% | 11.6% |
| Vulvovaginal pruritus (women) | 0.0% | 1.6% | 3.2% |
| Male genital mycotic infections (men: N=334, 408, 404) | 0.7% | 4.2% | 3.8% |
One monotherapy trial and three add-on trials with metformin, metformin and a sulfonylurea, or metformin and pioglitazone; 1,275 people took canagliflozin with metformin. Percentages were weighted by trials. Female and male genital yeast infection rates use the number of women or men in each group.
Abdominal pain was also more common on canagliflozin 100 mg (1.8%) and 300 mg (1.7%) than on placebo (0.8%).
When canagliflozin and metformin were started together, diarrhea was 4.2% in the combination groups vs 1.7% on either one alone.
In the three metformin add-on trials, side effects were similar to Table 3, with none added.
In CREDENCE (diabetic kidney disease), lower limb amputation was 12.3 vs 11.2 events per 1,000 patient-years on canagliflozin 100 mg vs placebo, and low blood pressure 2.8% vs 1.5%.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Lactic acidosis. The boxed-warning risk. Starting Invokamet is not recommended with an eGFR below 45, and it is not used below 30. It is stopped around some iodinated contrast scans, paused while food and fluids are restricted, stopped in shock, heart attack, sepsis or acute heart failure with low oxygen, and avoided with liver disease.
Ketoacidosis. Ketoacidosis can happen whatever the blood sugar. Ketone checks may be considered in people at risk, and Invokamet is stopped if it is suspected. It is not recommended in type 1 diabetes.
Lower limb amputation. People are watched for infections or ulcers of the legs and feet, which are treated.
Volume depletion. Fluid loss may lead to acute kidney injury. Fluid status is checked and corrected before starting in people with kidney problems, older people and people on loop diuretics.
Urinary and genital infections, including Fournier's gangrene. Serious urinary infections, kidney infections, genital yeast infections and a rare serious genital-area infection (Fournier's gangrene) have been reported. Pain, redness or swelling in the genital area with fever or feeling unwell is checked right away.
Low blood sugar with insulin or a sulfonylurea. A lower dose of insulin or a medicine that makes the body release insulin may be considered.
Allergic reactions. Invokamet is stopped if an allergic reaction occurs, and the person is watched until it resolves.
Bone fracture. Factors that add to fracture risk are considered before starting.
Vitamin B12 deficiency. Metformin may lower vitamin B12. Blood counts are measured yearly and vitamin B12 every 2 to 3 years.
From the Medication Guide that comes with Invokamet:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.