Canagliflozin and Amputation Risk: What You Need to Know Today

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. One drug that’s sparked intense debate is canagliflozin - sold under the brand name INVOKANA®. It works well. It helps with weight loss, lowers blood pressure, and protects the kidneys. But it also carries a known risk: lower-limb amputation. Not everyone gets it. Not even close. But for some, the consequences are life-changing. So what does the evidence really say? And how do you stay safe if you’re on this drug?

What the Studies Actually Found

The alarm bells rang in 2017 after the CANVAS Program - a pair of large clinical trials - showed that people taking canagliflozin had about twice the risk of needing an amputation compared to those on placebo. The numbers weren’t huge: 4.2 to 5.5 amputations per 1,000 patient-years on canagliflozin, versus 2.8 on placebo. But when you’re talking about losing a toe, foot, or leg, even small percentages matter.

Most of these amputations were minor - toe or metatarsal. About 80% fell into this category. Still, any amputation is a major event. It changes how you walk, how you live, how you feel. And the risk wasn’t random. It showed up strongest in people who already had poor circulation, nerve damage, or prior foot ulcers. That’s not a coincidence. Canagliflozin seems to worsen problems that already exist.

Here’s the twist: this risk doesn’t seem to apply to all drugs in its class. Empagliflozin (Jardiance) and dapagliflozin (Farxiga) didn’t show the same signal in their own large trials. In fact, dapagliflozin showed a slight trend toward fewer amputations. That’s critical. It means the risk isn’t about being an SGLT2 inhibitor. It’s about canagliflozin specifically.

A 2023 meta-analysis of over 74,000 patients confirmed it: only canagliflozin had a statistically significant increase in amputation risk (OR 1.6). Other drugs in the class? No clear link. That’s why experts now treat this as a drug-specific issue, not a class-wide one.

Why Does This Happen?

We don’t have a perfect answer yet, but clues are piling up. Canagliflozin causes more fluid loss and greater drops in blood pressure than other SGLT2 inhibitors. That might reduce blood flow to already compromised feet. It also leads to more weight loss - about 2.8 kg on average - which can change pressure points on the feet. For someone with diabetic neuropathy (numbness), even a small change can mean unnoticed injury.

There’s also evidence it affects how the body handles inflammation and healing. In people with poor circulation, even a small blister or cut can turn into a deep ulcer. And once that happens, healing slows down. Add in reduced sensation - which many diabetics have - and the problem goes unnoticed until it’s too late.

The FDA removed its boxed warning in 2020, but that doesn’t mean the risk disappeared. It means the agency decided the benefits outweighed the risks for most people - especially those with kidney disease or heart failure. But they still require the risk to be clearly stated in the prescribing information. That’s a middle ground: acknowledge the danger, but don’t scare people off a drug that saves lives.

Who’s at Highest Risk?

Not everyone on canagliflozin needs to panic. But some people should avoid it entirely. The biggest red flags:

• History of foot ulcers or prior amputation
• Diagnosed peripheral artery disease (PAD)
• Diabetic neuropathy with loss of sensation
• Current smoker
• Absent or weak pulses in the feet

If you have two or more of these, most experts now recommend avoiding canagliflozin. The American Diabetes Association and podiatry groups agree: if your ankle-brachial index (ABI) is below 0.9 - a sign of blocked arteries in the legs - don’t start this drug. That’s now part of the 2025 ADA guidelines.

And here’s something many patients don’t know: the risk doesn’t go away after a few months. It builds over time. That’s why ongoing foot checks aren’t optional. They’re essential.

What You Should Do If You’re on Canagliflozin

If you’re already taking it, here’s what you need to do right now:

1. Check your feet every single day. Look for redness, swelling, cuts, blisters, or sores - even if you don’t feel pain.
2. Wash and dry your feet daily. Moisturize, but not between the toes.
3. Never go barefoot. Not even inside.
4. Wear well-fitting shoes. No tight socks or high heels.
5. See your podiatrist at least once a year - more if you have nerve damage.
6. Report any new pain, warmth, or skin changes to your doctor immediately. Don’t wait.

Don’t rely on feeling. If you have neuropathy, you won’t feel a blister forming. That’s why visual checks are non-negotiable.

Also, make sure your doctor knows your full history. If you’ve had foot problems before, your prescription might need to change. Many endocrinologists now switch patients to empagliflozin or dapagliflozin if they develop any foot issues - and many patients report improvement after the switch.

Real Stories From Real Patients

Online forums are full of stories. One Reddit user, u/DiabetesWarrior2020, shared that after 18 months on INVOKANA, he developed a non-healing ulcer that led to a toe amputation. His endocrinologist switched him to Jardiance right away. He says he’s been ulcer-free for two years now.

Another user, u/SugarFreeLife, has been on INVOKANA for three years with no foot problems. Their A1c dropped from 8.5% to 6.2%. They’re grateful.

Both are true. That’s the point. The drug works for some. It harms others. The difference? Risk factors and vigilance.

FDA data shows about 0.045% of canagliflozin users report amputations - that’s 1 in 2,200. For empagliflozin, it’s 0.0026% - 1 in 38,000. That’s a big gap. But even 1 in 2,200 is too many when you’re talking about losing a limb.

What’s Changing Now?

The landscape is evolving. In January 2024, the FDA required all SGLT2 inhibitors to include standardized foot care instructions in their medication guides. That’s new. It means every pharmacy must give you a clear, written reminder about foot checks.

Medicare data shows that 68% of new canagliflozin prescriptions in 2023 included this guide - up from 42% in 2017. That’s progress.

There’s also a new trial underway - FOOT-STEP - testing whether structured foot care programs can prevent amputations in high-risk patients on canagliflozin. Results aren’t due until 2026, but if they work, it could change how we prescribe this drug entirely.

Janssen, the maker of INVOKANA, is also testing a new extended-release version designed to lower peak drug levels. The theory? Lower spikes might mean less impact on blood flow. It’s in Phase 2 now. If it works, it could bring this drug back into favor for more people.

Alternatives That Work Just as Well

If you’re worried, you have options. Empagliflozin (Jardiance) and dapagliflozin (Farxiga) are just as effective at lowering blood sugar and protecting the heart and kidneys - without the same amputation risk. They’re also cheaper now, thanks to generics.

GLP-1 receptor agonists like semaglutide (Wegovy, Ozempic) and liraglutide (Victoza) offer even better heart and kidney protection, plus weight loss. They don’t carry amputation risk either.

The key isn’t avoiding SGLT2 inhibitors. It’s choosing the right one for your body. If you have foot problems, avoid canagliflozin. If you’re healthy and don’t have circulation issues, it might still be fine - but only if you’re checking your feet every day.

Bottom Line: It’s Not About Avoiding the Drug - It’s About Managing the Risk

Canagliflozin isn’t dangerous for everyone. But it’s not safe for everyone either. The data is clear: if you have poor circulation, nerve damage, or a history of foot ulcers, this drug increases your risk of amputation. That risk is real. It’s not theoretical. It’s documented in trials, in real-world reports, and in patient stories.

But here’s the good news: you can control it. Regular foot checks. Good shoes. No smoking. Seeing your podiatrist. Talking to your doctor about alternatives. These aren’t just tips - they’re lifesavers.

If you’re on canagliflozin and you’ve never checked your feet in the mirror? Do it today. If you’ve never had an ABI test? Ask your doctor. If you’ve had a foot ulcer before? Don’t ignore it. Don’t wait. This isn’t about fear. It’s about awareness.

The drug saves lives. But only if you’re watching your feet.