Invokana (canagliflozin): Uses, Benefits, and Side Effects
By Web Admin
Medical Disclaimer
This article is for informational purposes only and does not constitute medical advice. Always consult your physician or a qualified healthcare provider regarding any medical condition or treatment.
Key Takeaways
Invokana (canagliflozin) was the first SGLT2 inhibitor approved by the FDA in 2013 — it lowers A1C by about 0.7 to 1.0 percent with 2 to 3 kg weight loss and similar blood pressure reduction.
The CREDENCE trial showed a 30 percent reduction in kidney failure or cardiovascular death in patients with type 2 diabetes and significant CKD.
The CANVAS trial showed a 14 percent reduction in major cardiovascular events but also a roughly 2-fold increased risk of lower-limb amputation and an increased fracture signal.
Dosing is 100 mg or 300 mg once daily before the first meal of the day, with the 300 mg dose giving additional glycemic effect.
Invokana is less commonly prescribed today than Jardiance or Farxiga due to the amputation signal, but remains a useful option in selected patients — talk to your doctor about your individual risk profile.
Invokana (canagliflozin) was the first SGLT2 inhibitor approved by the FDA, in March 2013. It is an oral once-daily tablet that lowers blood sugar by causing glucose excretion in urine, with the typical SGLT2 inhibitor benefits — about 0.7 to 1.0 percent A1C reduction, 2 to 3 kg weight loss, and 3 to 5 mmHg blood pressure reduction. The CREDENCE trial showed strong kidney benefits in patients with diabetic nephropathy. However, the CANVAS trial revealed an increased risk of lower-limb amputation, which has limited its use compared with empagliflozin and dapagliflozin.
What Invokana Is
Feature
Detail
Active ingredient
Canagliflozin
Class
SGLT2 inhibitor
Manufacturer
Janssen (Johnson and Johnson)
FDA approval year
2013 — first SGLT2 inhibitor approved
Doses
100 mg, 300 mg
Frequency
Once daily, before first meal
Combination product
Invokamet (with metformin)
US generic available?
No (as of 2026)
How It Works
Blocks SGLT2 in the proximal tubule of the kidney
Causes about 50 to 80 grams of glucose excretion per day in urine
Effect is glucose-dependent — minimal hypoglycemia alone
Mild diuresis from osmotic glucose load in urine
Mild blood pressure reduction
Mild weight loss from urinary calorie loss
Some additional SGLT1 inhibition (more than empagliflozin / dapagliflozin), which slightly reduces postprandial glucose by delaying intestinal glucose absorption
The CANVAS Program
10,142 patients with T2D and high CV risk
Mean follow-up 3.6 years
14 percent reduction in major cardiovascular events (MACE)
33 percent reduction in heart failure hospitalization
40 percent reduction in renal endpoints
Increased amputation risk — 6.3 vs 3.4 per 1,000 patient-years
Increased fracture risk in the CANVAS portion (not seen in CANVAS-R)
Original FDA boxed warning for amputation later removed in 2020
The CREDENCE Trial
Aspect
CREDENCE Detail
Participants
4,401 with T2D and CKD (eGFR 30 to 90, UACR above 300 mg/g)
Treatment
Canagliflozin 100 mg vs placebo
Median follow-up
2.6 years
Primary outcome
30 percent reduction in kidney failure / CV death
CV death or HF hospitalization
31 percent reduction
End-stage kidney disease
32 percent reduction
Amputation signal
Not confirmed in CREDENCE — similar to placebo
Dosing
Start at 100 mg once daily, before the first meal of the day
Increase to 300 mg if additional glycemic control needed and eGFR is sufficient
For diabetic kidney disease (CREDENCE indication) — 100 mg maintained even at lower eGFR
eGFR cutoff for initiation — generally not below 30 mL/min/1.73 m²
Discontinue at end-stage renal disease or dialysis
Take consistently at the same time each day
Side Effects
Side Effect
Frequency
Notes
Genital yeast infection
10 to 15 percent
Slightly higher than empagliflozin in some studies
Urinary tract infection
5 to 9 percent
Similar to class
Increased urination
3 to 5 percent
Similar to class
Volume depletion
2 to 4 percent
Especially in elderly and on diuretics
Lower-limb amputation
About 2x in CANVAS
Highest risk if PAD or prior amputation
Bone fracture
Increased in CANVAS
Not confirmed in all subsequent studies
Hyperkalemia
Slightly increased
Particularly with RAAS inhibitors
Euglycemic DKA
Less than 0.1 percent
Class effect
Fournier gangrene
Very rare
Class boxed warning
Who Should Avoid Invokana
Prior lower-limb amputation
Active foot ulcer or significant diabetic foot disease
Severe peripheral artery disease
Type 1 diabetes
Dialysis
Recurrent genital or urinary infections
Pregnancy
Significant osteoporosis or high fracture risk (relative caution)
Who May Benefit
Type 2 diabetes with diabetic kidney disease and significant proteinuria (CREDENCE data)
Type 2 diabetes with established CV disease and no foot risk factors
Patients without amputation, PAD, or active foot disease
Invokana (canagliflozin) was the first SGLT2 inhibitor approved by the FDA. It lowers A1C by about 0.7 to 1.0 percent, produces 2 to 3 kg weight loss, and reduces blood pressure modestly. The CREDENCE trial showed strong kidney protection in diabetic nephropathy, with a 30 percent reduction in kidney failure or CV death. However, the CANVAS trial revealed an increased lower-limb amputation risk, which led to historic FDA warnings and a shift in prescribing toward empagliflozin and dapagliflozin for many patients. Invokana remains a useful option in selected patients — particularly those with diabetic kidney disease and proteinuria, no foot risk factors, and tolerance for before-meal dosing. Talk to your doctor about whether Invokana fits your individual cardiovascular, kidney, and foot risk profile.
Frequently Asked Questions
Is Invokana the same as Jardiance?
No, but they are in the same class. Invokana is canagliflozin and Jardiance is empagliflozin — both SGLT2 inhibitors that work by the same mechanism of blocking renal glucose reabsorption. They have similar A1C, weight, and blood pressure effects. The main differences are Invokana's historic amputation and fracture signals from the CANVAS trial, which are not seen with empagliflozin or dapagliflozin. Invokana is also taken before the first meal, while Jardiance can be taken any time.
Does Invokana really increase amputation risk?
The CANVAS trial showed about a 2-fold increased risk of lower-limb amputation, primarily toe or metatarsal level — absolute risk was 6.3 per 1,000 patient-years on canagliflozin versus 3.4 on placebo. The FDA initially required a boxed warning, then removed it in 2020 after additional data including CREDENCE did not confirm the same magnitude of risk. The signal appears strongest in patients with prior amputation, peripheral artery disease, or active foot ulcers. Risk in patients without these factors is much lower.
What is Invokana approved for?
Invokana is FDA-approved for type 2 diabetes to improve glycemic control. It also has indications for reducing major cardiovascular events in T2D with established CV disease (CANVAS data) and for diabetic kidney disease with significant albuminuria (CREDENCE data). It is not approved for heart failure as a primary indication in the way Jardiance and Farxiga are. It is also not approved for type 1 diabetes.
Why is Invokana taken before the first meal?
Canagliflozin is best absorbed and most effective when taken about 30 minutes before the first meal of the day. Taking it after eating can reduce peak drug levels and modestly reduce glycemic effect. This timing difference is unique to canagliflozin among the major SGLT2 inhibitors — Jardiance and Farxiga can be taken with or without food at any time.
Is Invokana still used or is it outdated?
Still used, but less commonly than empagliflozin or dapagliflozin. The amputation and fracture signals from CANVAS, combined with the lack of dedicated heart failure indication, have shifted prescribing toward Jardiance and Farxiga for many patients. Invokana remains a reasonable option in patients without amputation risk factors, particularly those with diabetic kidney disease and proteinuria where CREDENCE evidence is strong. Insurance formulary preferences also drive some prescribing.
Sources
Neal B, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS Program). N Engl J Med. 2017;377:644-657.
Perkovic V, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (CREDENCE). N Engl J Med. 2019;380:2295-2306.
U.S. Food and Drug Administration. Invokana (Canagliflozin) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
