SGLT2 Inhibitors and Bone Health: What You Need to Know About Fracture Risk

When you're managing type 2 diabetes, choosing the right medication isn't just about lowering blood sugar. It's about balancing benefits with hidden risks - and one of the most confusing concerns lately is bone health. Specifically, could your SGLT2 inhibitor be making you more likely to break a bone? The answer isn't simple, and it depends heavily on which drug you're taking.

What Are SGLT2 Inhibitors?

SGLT2 inhibitors are a group of diabetes drugs that work differently from most others. Instead of pushing insulin out or making cells more sensitive to it, they tell your kidneys to dump extra sugar into your urine. That lowers blood glucose without causing low blood sugar or weight gain - two big wins. Common ones include canagliflozin (Invokana), empagliflozin (Jardiance), and dapagliflozin (Farxiga). They’re also known for protecting your heart and kidneys, which is why so many doctors prescribe them.

But in 2015, something unexpected popped up. The CANVAS trial, a major study on canagliflozin, showed more bone fractures in people taking it compared to those on placebo. That triggered a red flag from the FDA. Suddenly, patients and doctors were asking: Is this a one-drug problem? Or does it apply to all SGLT2 inhibitors?

Canagliflozin and the Fracture Risk Signal

The data on canagliflozin is clear: it carries a higher fracture risk than other drugs in its class. In the CANVAS trial, people on canagliflozin had about 15 fractures per 1,000 patient-years, compared to 12 per 1,000 on placebo. That’s a 26% increase. The fractures weren’t from car crashes or sports injuries - they happened after simple falls, like stepping off a curb or slipping in the shower. Most occurred within the first 12 weeks of starting the drug.

Why? Three main theories exist. First, canagliflozin causes mild bone mineral density loss - about 1% at the hip and spine over two years, according to FDA-mandated studies. Second, it lowers estrogen levels slightly in women, which can weaken bone. Third, it can cause dizziness or low blood pressure when standing, increasing fall risk. These effects don’t happen with the same intensity in other SGLT2 inhibitors.

Here’s what’s important: the FDA only added a fracture warning to canagliflozin’s label - not to empagliflozin or dapagliflozin. That’s not an accident. It’s based on real data.

Other SGLT2 Inhibitors: Safer for Bones?

When you look at empagliflozin and dapagliflozin, the story changes. The EMPA-REG OUTCOME trial (2015) and DECLARE-TIMI 58 (2019) found no increased fracture risk with either drug. A 2023 meta-analysis of 27 clinical trials involving over 20,000 patients showed no overall link between SGLT2 inhibitors and fractures - except when canagliflozin was included. When researchers pulled canagliflozin out of the data, the risk vanished.

Real-world studies back this up. A 2023 analysis in the Journal of Parathyroid Disease reviewed patient records from over 50,000 people and found no connection between empagliflozin or dapagliflozin use and fractures. Even better: a 2023 study in JAMA Network Open showed that SGLT2 inhibitors overall had similar or even lower fracture rates than GLP-1 agonists and DPP-4 inhibitors - two other popular diabetes drug classes.

So if you're on empagliflozin or dapagliflozin, your fracture risk is likely no higher than if you weren’t taking any of these drugs at all.

Who’s at Highest Risk?

Not everyone on canagliflozin will break a bone. But some people are more vulnerable. The biggest risk factors include:

• Age over 65
• History of previous fractures
• Diagnosed osteoporosis (T-score ≤ -2.5)
• Low body weight or muscle mass
• History of falls or balance problems
• Long-term steroid use

Women, especially postmenopausal women, are more affected by the estrogen-lowering effect of canagliflozin. A clinical trial showed a 9.2% drop in estradiol levels after 24 weeks of 300 mg daily - enough to matter for bone health.

Dr. Sarah Chen, an endocrinologist at Mayo Clinic, says she avoids canagliflozin entirely in patients with osteoporosis or prior fractures. “I’ve seen three or four fractures per 1,000 patient-years with canagliflozin in elderly, high-risk patients,” she says. “That’s enough to change my prescribing habits.”

What Should You Do Before Starting?

If your doctor suggests an SGLT2 inhibitor, ask: Which one? And why?

For canagliflozin, the American Association of Clinical Endocrinologists (AACE) recommends checking your bone density with a DXA scan if you have any of the risk factors listed above. If your hip or spine T-score is below -2.0, they advise choosing another drug.

The American Diabetes Association’s 2023 guidelines now include a small adjustment to the FRAX fracture risk score - adding 0.5 points if you’re taking canagliflozin. No adjustment is made for empagliflozin or dapagliflozin. That’s a subtle but important distinction.

Here’s a quick checklist before starting any SGLT2 inhibitor:

1. Do you have a history of fractures or osteoporosis?
2. Are you over 65 or have balance issues?
3. Are you on other medications that cause dizziness?
4. Have you had a fall in the past year?

If you answered yes to any of these, talk to your doctor about switching to empagliflozin or dapagliflozin - unless there’s a strong reason not to.

Why the Confusion? The Data Is Messy

Why do some studies say there’s no risk, while others say there is? It comes down to how the data is grouped. Early studies lumped all SGLT2 inhibitors together. That masked the fact that canagliflozin was driving the risk. Later analyses that separated the drugs revealed the truth: the class isn’t the problem - one drug is.

Also, many trials were designed to study heart and kidney outcomes, not bones. They weren’t powered to detect small differences in fracture rates. Dr. Robert Heaney, a leading bone expert, points out that the number of fractures in these trials was too low to be statistically reliable. “We need longer follow-up,” he says. “We’re still missing part of the picture.”

But here’s what we know now: if you’re healthy and have no bone issues, any SGLT2 inhibitor is likely safe. If you’re at risk for fractures, avoid canagliflozin.

What About Other Diabetes Drugs?

It’s worth comparing SGLT2 inhibitors to other options. GLP-1 agonists like semaglutide (Ozempic) and liraglutide (Victoza) are popular, but they can cause nausea and vomiting - which increases fall risk in older adults. DPP-4 inhibitors like sitagliptin (Januvia) are neutral for bone health but offer less heart and kidney protection. Metformin? It’s safe for bones, but doesn’t protect the heart like SGLT2 inhibitors do.

For most people with diabetes and heart or kidney disease, the benefits of SGLT2 inhibitors outweigh the risks - as long as you pick the right one.

What’s Changing in 2025?

The field is evolving fast. The American Diabetes Association and European Association for the Study of Diabetes are preparing a new consensus report expected in early 2025. It will likely formalize the idea that canagliflozin should be avoided in high-risk bone patients - while other SGLT2 inhibitors remain first-line options.

Prescription trends already reflect this. Between 2017 and 2022, canagliflozin use dropped 22% in the U.S. Empagliflozin and dapagliflozin prescriptions rose by over 40%. The American Geriatrics Society’s 2023 Beers Criteria lists canagliflozin as “potentially inappropriate” for older adults with osteoporosis - but doesn’t mention the others.

Pharmacies and insurers are catching up too. Some now require pre-authorization for canagliflozin if you have a history of fractures.

Bottom Line: Know Your Drug, Know Your Risk

Don’t panic if you’re on an SGLT2 inhibitor. But do pay attention to which one.

If you’re on empagliflozin or dapagliflozin: your bone health is likely unaffected. Continue taking it - the heart and kidney benefits are real.

If you’re on canagliflozin and have osteoporosis, a past fracture, or are over 65 with balance issues: talk to your doctor about switching. The risk isn’t huge, but it’s real - and avoidable.

And if you’re just starting diabetes meds? Ask your doctor: “Which SGLT2 inhibitor are you recommending, and why?” Don’t assume they’re all the same. They’re not.