Canagliflozin Amputation Risk: What You Need to Know Now

Posted By Simon Woodhead On 22 Nov 2025 Comments(1)

Canagliflozin Amputation Risk Assessment

Assess Your Personal Risk

This tool helps you understand your personal risk of foot and leg amputation while taking canagliflozin based on your medical history. It's based on current clinical evidence from the CANVAS Program and other studies.

How long have you been taking canagliflozin?

Do you have peripheral artery disease (PAD)?

Do you have diabetic neuropathy (nerve damage)?

Have you had previous foot ulcers or amputations?

Do you currently smoke?

Do you have absent or weak foot pulses?

Do you have kidney disease or heart disease?

When you're managing type 2 diabetes, choosing the right medication isn't just about lowering blood sugar. It's about balancing benefits with real, sometimes serious, risks. Canagliflozin, sold under the brand name INVOKANA®, is one of those drugs that changed the game - but not without controversy. In 2017, a major study found it doubled the risk of foot and leg amputations. That sent shockwaves through the medical world. Today, the FDA removed its strongest warning, but the risk hasn't disappeared. If you're on canagliflozin, or your doctor is considering it, you need to know what’s real, what’s been cleared up, and most importantly - how to protect yourself.

What Happened With Canagliflozin and Amputations?

The alarm started with the CANVAS Program, a pair of large clinical trials involving over 10,000 people with type 2 diabetes and heart disease. Researchers found that those taking canagliflozin had about twice as many amputations as those on placebo. The numbers weren’t small: 4.2 to 5.5 amputations per 1,000 people each year on canagliflozin, compared to just 2.8 on placebo. That’s a real increase - not a statistical fluke. Most of these were minor amputations - toes or parts of the foot - but about 1 in 5 were above the ankle. That’s life-changing.

The FDA responded quickly. In June 2017, they added a boxed warning - the strongest possible alert - saying canagliflozin could cause amputations. For a while, many doctors stopped prescribing it. Patients panicked. But here’s where it gets complicated.

In 2020, after reviewing more data - including the CREDENCE trial that showed canagliflozin significantly reduced kidney failure and heart death in high-risk patients - the FDA removed the boxed warning. They didn’t say the risk was gone. They said the benefits outweighed the risks for many people, especially those with kidney disease. But they kept the warning in the prescribing information. It’s still there, updated as recently as April 2025.

Is This Risk the Same for All SGLT2 Inhibitors?

This is critical. Canagliflozin is not like other drugs in its class. SGLT2 inhibitors include empagliflozin (Jardiance), dapagliflozin (Farxiga), and others. But the amputation risk doesn’t follow the class. It follows canagliflozin.

Multiple studies confirm this. The EMPA-REG OUTCOME trial with empagliflozin showed no increased amputation risk. The DECLARE-TIMI 58 trial with dapagliflozin even showed a slight reduction. A 2023 meta-analysis of over 74,000 patients found that only canagliflozin had a statistically significant link to amputation - an odds ratio of 1.6. For every 556 people treated with canagliflozin for one year, one extra amputation occurred. That’s not common, but it’s enough to matter.

Why does this happen only with canagliflozin? Scientists aren’t sure. One theory points to its stronger effect on lowering blood pressure and body weight compared to other SGLT2 inhibitors. In people with poor circulation - common in diabetes - that drop in pressure might reduce blood flow to the feet just enough to turn a small sore into a fatal problem. Another idea: canagliflozin might affect how the body handles inflammation or healing in ways the others don’t. Whatever the reason, the data is clear: if you’re worried about amputation risk, don’t assume all SGLT2 inhibitors are the same.

Who’s Most at Risk?

The risk isn’t spread evenly. If you have no foot problems, no history of ulcers, no nerve damage, and good circulation, your chance of needing an amputation on canagliflozin is very low. But if you have any of these, your risk jumps:

Peripheral artery disease (PAD) - narrowed arteries in your legs. Affects 20-30% of people with diabetes.
Diabetic neuropathy - nerve damage that makes you lose feeling in your feet. Affects about half of all diabetics.
Previous foot ulcers or amputations - if you’ve had one, you have a 40% chance of another within a year.
Smoking - it damages blood vessels and slows healing.
Absent or weak foot pulses - a simple sign your doctor can check.

The American Diabetes Association and podiatry groups now recommend that anyone with two or more of these risk factors should avoid canagliflozin entirely. Instead, choose empagliflozin or dapagliflozin - they offer similar heart and kidney protection without the same amputation signal.

Doctor tests ankle blood flow on one side, injured foot with missing toe on the other, medical icons floating.

What Should You Do If You’re on Canagliflozin?

If you’re already taking it, don’t stop cold turkey. Talk to your doctor. But here’s what you need to do right now:

Check your feet daily. Look for redness, swelling, cuts, blisters, or sores - even if you don’t feel pain. Nerve damage hides symptoms.
Report anything unusual immediately. New pain, warmth, odor, or drainage from your foot? Call your doctor the same day. Don’t wait. Delayed care is what turns small problems into amputations.
Get a foot exam at every visit. Your doctor should check pulses, sensation, and skin condition every time you see them - not just once a year.
Ask for an ankle-brachial index (ABI) test. This simple, painless test compares blood pressure in your arms and ankles. If it’s below 0.9, you have significant artery blockage. In 2024, the ADA recommended this test before starting canagliflozin if you have any heart disease or vascular risk.
Know your alternatives. If you have risk factors, ask: Is there a safer SGLT2 inhibitor for me? Jardiance and Farxiga are strong options.

Real Stories, Real Risks

Online forums like PatientsLikeMe and Reddit show this isn’t just theory. One user, u/DiabetesWarrior2020, shared that after 18 months on INVOKANA, he developed a foot ulcer that didn’t heal. He lost a toe. His endocrinologist switched him to Jardiance right away. Another user, u/SugarFreeLife, said she’s been on it for three years with no foot issues - and her A1C dropped from 8.5% to 6.2%.

The FDA’s own drug safety database shows something startling: for every 1 million prescriptions of canagliflozin, there are about 45 amputation reports. For empagliflozin, it’s just 3. That’s a 15-fold difference in reporting rates. These aren’t just numbers. They’re people.

How Are Doctors Adjusting?

Prescribing patterns have changed. In 2017, canagliflozin made up 35% of all SGLT2 inhibitor prescriptions. By 2023, that dropped to 22%. But it didn’t vanish. Why? Because for some patients - especially those with kidney disease and no foot problems - the benefits are too good to ignore. Canagliflozin reduces heart failure hospitalizations, slows kidney decline, and helps with weight loss.

Now, doctors are more careful. In 2023, 68% of new canagliflozin prescriptions in Medicare included a medication guide warning about amputation - up from 42% in 2017. That means patients are being told more clearly. And the FDA now requires all SGLT2 inhibitors to include standardized foot care advice in their patient guides.

Three patients at a medical crossroads: one with damaged foot, one with healthy feet, one guided by a podiatrist.

What’s Next?

Research is still ongoing. The FOOT-STEP trial, expected to finish in late 2026, is testing whether structured foot care - daily checks, podiatrist visits, education - can actually prevent amputations in high-risk patients on canagliflozin. Early results are promising.

Janssen, the maker of INVOKANA, is also testing a new extended-release version (INVOKANA XR) that releases the drug more slowly. The theory? Lower peak levels in the blood might reduce the blood pressure drop that could trigger circulation problems. It’s still in early trials, but it’s a sign the company is listening.

The Bottom Line

Canagliflozin is not a dangerous drug for everyone. But it’s not risk-free. For people with diabetes and existing foot or circulation problems, it’s a bad choice. For others, it can be a lifesaver - if used with eyes wide open.

Your job isn’t to avoid all risk. It’s to understand your personal risk and take control. Ask your doctor: Do I have PAD or neuropathy? Have I had foot ulcers? Are my foot pulses strong? Should I get an ABI test? Is there a safer alternative?

The goal isn’t to scare you off a medication. It’s to make sure you’re not blindsided. Diabetes management is a team effort - between you, your doctor, and your podiatrist. If you’re on canagliflozin, make sure your feet are part of every conversation.

Is canagliflozin still prescribed today?

Yes, but more cautiously. In 2023, it accounted for 22% of SGLT2 inhibitor prescriptions in the U.S., down from 35% in 2017. Doctors still prescribe it for patients with type 2 diabetes who have heart failure, kidney disease, or need help with weight loss - but only if they don’t have foot or circulation problems. The key is patient selection.

Are all SGLT2 inhibitors equally risky for amputation?

No. Only canagliflozin has shown a clear, consistent increase in amputation risk across multiple large studies. Empagliflozin (Jardiance) and dapagliflozin (Farxiga) have not shown this risk in their major trials. If amputation risk is a concern, these alternatives are preferred, especially for patients with existing foot complications or poor circulation.

What should I do if I notice a sore on my foot while taking canagliflozin?

Call your doctor or podiatrist immediately - do not wait. Even small sores can turn serious quickly in people with diabetes, especially if you have nerve damage. Don’t try to treat it yourself. Early intervention - cleaning, offloading pressure, antibiotics if needed - can prevent amputation. The FDA and ADA both stress that patients should report any new pain, redness, swelling, or drainage in their feet or legs without delay.

Can I switch from canagliflozin to another SGLT2 inhibitor?

Yes, and many doctors recommend it if you have risk factors like neuropathy, PAD, or a history of foot ulcers. Empagliflozin and dapagliflozin offer similar benefits for heart and kidney protection without the same amputation signal. Switching is usually safe and well-tolerated, but always do it under medical supervision to avoid blood sugar spikes.

How often should I get my feet checked if I’m on canagliflozin?

At every doctor’s visit - not just annually. The American Diabetes Association recommends a full foot exam including pulse checks and sensation testing every time you see your provider. If you have risk factors, you should also see a podiatrist every 2-3 months. Daily self-checks at home are non-negotiable. Use a mirror or ask someone to help you look for changes you can’t see.

Does the FDA still consider canagliflozin safe?

The FDA removed its boxed warning in 2020 after reviewing additional data showing that the benefits for kidney and heart protection outweighed the amputation risk in certain patients - particularly those with diabetic kidney disease. However, the prescribing information still includes a warning about amputation risk. The agency considers it safe for appropriate patients, but only when used with proper monitoring and patient selection.

Next Steps If You’re on Canagliflozin

If you’re taking canagliflozin, here’s your action plan:

Do this today: Look at your feet. Are there any cracks, sores, or discoloration?
Do this this week: Call your doctor. Ask: “Do I have any risk factors for amputation? Should I get an ABI test?”
Do this next visit: Request a full foot exam - pulses, sensation, skin condition.
Do this monthly: Review your foot care routine. Are you checking daily? Are you wearing proper shoes?
Do this if you’re unsure: Ask for a referral to a podiatrist. They specialize in diabetic foot care and can spot problems before they become emergencies.

The goal isn’t to fear your medication. It’s to use it wisely. Canagliflozin can be a powerful tool - but only if you’re watching your feet as closely as you’re watching your blood sugar.