When you’re managing type 2 diabetes, finding a medication that lowers blood sugar and protects your heart is a win. But for some people taking canagliflozin (brand name INVOKANA®), that win came with a hidden cost: an increased risk of losing a toe, foot, or even part of a leg. This isn’t fear-mongering. It’s data. And it’s real.
What Happened with Canagliflozin?
Canagliflozin was approved in 2013 as part of a new class of diabetes drugs called SGLT2 inhibitors. These drugs work by making your kidneys flush out extra sugar through urine - a clever trick that lowers blood glucose without causing weight gain or low blood sugar. Early studies showed it also reduced heart failure and kidney damage in high-risk patients. That’s why it quickly became popular. Then, in 2017, the CANVAS Program - a major clinical trial involving over 10,000 people - dropped a bombshell. People taking canagliflozin were more than twice as likely to have a lower-limb amputation compared to those on placebo. The numbers were stark: 5.5 amputations per 1,000 patient-years at the higher dose (300 mg), versus 2.8 in the placebo group. Most were minor - toes or parts of the foot - but 20% were major, above the ankle. The FDA responded immediately. They added a boxed warning - the strongest possible alert - to the drug label. Doctors were told to avoid prescribing it to patients with poor circulation, foot ulcers, or nerve damage. Many stopped using it altogether.But Then… The Warning Was Removed
By early 2020, the FDA quietly removed the boxed warning. Not because the risk disappeared. But because they re-evaluated everything - including the CREDENCE trial, which showed canagliflozin dramatically slowed kidney disease progression in people with diabetic nephropathy. The benefits, especially for high-risk kidney patients, were too big to ignore. Today, the risk is still there. It’s just no longer labeled as a “boxed warning.” Instead, it’s clearly stated in the Warnings and Precautions section of the prescribing information. The FDA still says: “Monitor for new pain, tenderness, sores, ulcers, or infections in the legs or feet.” And they mean it.Is This Risk Unique to Canagliflozin?
This is the most important question. And the answer is yes - at least for now. Other SGLT2 inhibitors like empagliflozin (Jardiance) and dapagliflozin (Farxiga) have been studied just as hard. In the EMPA-REG OUTCOME trial, empagliflozin showed no increased amputation risk. In fact, dapagliflozin’s DECLARE-TIMI 58 trial showed a slight trend toward fewer amputations. A 2023 meta-analysis of over 74,000 patients confirmed: only canagliflozin had a statistically significant link to amputation. Why? We don’t fully know. But clues point to how canagliflozin affects the body. It lowers blood pressure more than other drugs in its class - by about 3.7 mmHg systolic. It also causes greater weight loss - nearly 3 kg on average. In people with already compromised circulation, that drop in pressure and volume might reduce blood flow to the feet just enough to turn a small sore into a life-altering problem.
Who’s Really at Risk?
Not everyone on canagliflozin will have an amputation. The absolute risk is low. One study estimated that for every 556 people treated for a year, only one extra amputation occurs. That’s rare. But rare doesn’t mean harmless - especially if you’re in the high-risk group. The real danger lies in pre-existing conditions:- Peripheral artery disease (PAD) - present in 20-30% of people with type 2 diabetes
- Diabetic neuropathy - affects up to half of all patients
- History of foot ulcers - 40% of those who’ve had one will get another within a year
- Smoking - doubles the risk of poor circulation
- Prior amputation - the single biggest predictor of future amputation
What Should You Do If You’re on Canagliflozin?
If you’re already taking it, don’t panic. But do take action. 1. Get a foot exam - now. Your doctor should check for pulses, sensation, skin changes, and any sores. If you haven’t had one in the last 6 months, schedule one. The American Diabetes Association now recommends an ankle-brachial index (ABI) test before starting canagliflozin if you have any cardiovascular risk factors. An ABI below 0.9 means poor leg circulation - and it’s a red flag. 2. Check your feet daily. Use a mirror. Look between toes. Feel for warmth, swelling, or new pain. Even a small blister can turn into an ulcer if you have nerve damage and don’t feel it. The NICE guidelines say: “Report any new foot problem immediately - don’t wait.” 3. Talk to your doctor about alternatives. If you have risk factors, switching to empagliflozin or dapagliflozin may be safer. Both have proven heart and kidney benefits without the amputation signal. Jardiance and Farxiga are now the go-to SGLT2 inhibitors for most clinicians. 4. Know the signs. Redness, swelling, warmth, drainage, odor, or non-healing sores? Don’t wait for your next appointment. Call your podiatrist or endocrinologist. Time is tissue.Real Stories - Not Just Numbers
On PatientsLikeMe, 6.9% of canagliflozin users reported foot problems. A Reddit user named u/DiabetesWarrior2020 shared: “After 18 months on Invokana, my podiatrist found a non-healing ulcer. I lost my toe. My endocrinologist switched me to Jardiance the next day.” Another user, u/SugarFreeLife, wrote: “Three years on Invokana. No foot issues. My A1c dropped from 8.5% to 6.2%.” Both are true. That’s the problem - and the solution. It’s not about the drug being “bad.” It’s about matching the right drug to the right person.
What’s Changing Now?
The landscape is shifting. In January 2024, the FDA required all SGLT2 inhibitors to include standardized foot care counseling in their medication guides. That means every prescription now comes with clear instructions on foot checks and warning signs. Janssen, the maker of INVOKANA, is testing a new extended-release version (INVOKANA XR) that may reduce peak drug levels - and possibly lower the amputation risk. Early data is promising. The FOOT-STEP trial, running until 2026, is testing whether structured foot care programs - weekly check-ins, custom footwear, rapid ulcer treatment - can prevent amputations in high-risk patients on canagliflozin. Results could change everything.The Bottom Line
Canagliflozin is not banned. It’s not evil. It’s a powerful tool - but only for the right patient. For someone with heart failure, kidney disease, and no foot problems? It can be life-saving. For someone with numb feet, smoking, and poor circulation? It’s a gamble you shouldn’t take. The key isn’t avoiding the drug entirely. It’s knowing who it’s safe for - and who it’s not. If you’re on canagliflozin, ask your doctor: “Do I have any risk factors for foot problems?” If you’re considering it, ask: “Is this the safest SGLT2 inhibitor for me?” The data is clear. The tools are there. And the choice? That’s yours - with the right information.Is canagliflozin still prescribed today?
Yes, but more cautiously. In 2023, canagliflozin made up 22% of SGLT2 inhibitor prescriptions in the U.S., down from 35% in 2017. Doctors now avoid it in patients with foot ulcers, poor circulation, or neuropathy. It’s still used in patients with heart or kidney disease who don’t have those risk factors.
How common are amputations with canagliflozin?
Very rare overall. About 5.5 out of every 1,000 people taking the 300 mg dose had an amputation per year - compared to 2.8 per 1,000 on placebo. That’s roughly 1.8 extra amputations per 1,000 patient-years. But for people with existing foot problems, the risk is much higher.
Are all SGLT2 inhibitors equally risky?
No. Only canagliflozin has shown a consistent, statistically significant increase in amputation risk. Empagliflozin (Jardiance) and dapagliflozin (Farxiga) have not shown this signal in major trials. Many doctors now prefer these alternatives for patients with any foot or circulation concerns.
What should I do if I notice a sore on my foot while taking canagliflozin?
Call your doctor or podiatrist immediately. Don’t wait. Even a small blister can become a serious infection if you have nerve damage. Early treatment - cleaning, offloading pressure, antibiotics if needed - can prevent amputation. The FDA and NICE both stress: report foot changes right away.
Can I switch from canagliflozin to another diabetes drug safely?
Yes, and many people do - especially if they have foot or circulation issues. Empagliflozin and dapagliflozin are common switches. Both offer similar blood sugar control and heart/kidney benefits without the amputation signal. Your doctor will monitor your blood sugar closely during the transition.
Does the FDA still consider canagliflozin safe?
The FDA removed the boxed warning in 2020 after reviewing more data, but it still lists amputation risk in the Warnings and Precautions section. They say the benefits outweigh the risks for certain patients - especially those with kidney disease - but only if foot health is monitored. They now require all SGLT2 inhibitors to include foot care education in their packaging.
Comments (1)
Bennett Ryynanen December 30 2025
Bro, I lost my toe on this drug. No joke. Wasn't even smoking, no ulcers, just numb feet from diabetes. Doctor swore it was fine. Turns out, the FDA warning was buried in the tiny print. Now I walk with a cane and a chip on my shoulder. Don't let them gaslight you into thinking it's 'rare' - if it happens to you, it's 100%.