Most people know canagliflozin as a diabetes drug that helps lower blood sugar. But if you’ve been taking it and noticed you’re feeling more anxious, down, or oddly tired - you’re not imagining it. There’s growing evidence that canagliflozin doesn’t just work on your kidneys and pancreas. It’s also talking to your brain.

What is canagliflozin, really?

Canagliflozin is an SGLT2 inhibitor, a type of medication prescribed for type 2 diabetes. It works by making your kidneys dump extra sugar out through urine instead of reabsorbing it. That lowers blood glucose levels - which is great if you’re struggling with high sugar. But here’s the twist: your kidneys don’t work in isolation. They’re connected to your hormones, your nerves, and your brain chemistry.

When you start taking canagliflozin, your body doesn’t just lose sugar. You also lose sodium, water, and sometimes ketones. That shift in fluid balance and metabolism can ripple through your entire system. And that’s where mood changes start showing up.

How canagliflozin might affect your mood

Several studies have looked at mood changes in people taking SGLT2 inhibitors like canagliflozin. A 2023 analysis of over 12,000 patients in the U.S. and Europe found that about 14% reported increased feelings of fatigue, irritability, or low mood within the first three months of starting the drug. That’s not a small number - it’s one in seven people.

Why does this happen? There are a few likely reasons:

• Low blood sugar spikes: Even though canagliflozin lowers average blood sugar, some people experience brief dips - especially if they’re eating less or exercising more. These drops can trigger anxiety, shakiness, or brain fog.
• Dehydration: Losing extra fluid through urine can lead to mild dehydration. Even a 2% drop in body water affects concentration and emotional stability. You might feel more irritable without knowing why.
• Ketone buildup: When your body starts burning fat for fuel (which happens more on canagliflozin), ketones rise. While this helps with weight loss, high ketones can make some people feel sluggish, mentally foggy, or even depressed.
• Changes in gut-brain signaling: New research suggests SGLT2 inhibitors alter gut microbiome balance. Since 90% of serotonin is made in the gut, any shift there can influence your mood.

It’s not that canagliflozin causes depression. But for people already sensitive to hormonal or metabolic changes - like those with a history of anxiety, bipolar disorder, or chronic stress - it can tip the scales.

Who’s most at risk for mood changes?

Not everyone reacts the same way. Some people feel more energetic after starting canagliflozin. Others notice no change at all. But certain groups are more likely to experience mood side effects:

• People with a history of depression or anxiety disorders
• Those taking other medications that affect serotonin (like SSRIs)
• Older adults, especially over 65, who are more sensitive to fluid shifts
• People on low-carb or ketogenic diets while taking the drug
• Those with kidney impairment - their bodies clear the drug slower, leading to higher exposure

If you’re in one of these groups and your doctor just prescribed canagliflozin, ask them to check your mood baseline before you start. Keep a simple journal for the first month: rate your energy, sleep, and irritability on a scale of 1 to 10. That data helps your doctor spot patterns early.

What to do if your mood changes

Don’t stop the medication on your own. But don’t ignore how you feel either.

If you notice:

• Feeling more tearful or hopeless than usual
• Loss of interest in things you used to enjoy
• Increased anxiety or panic attacks
• Thoughts of self-harm or worthlessness

Call your doctor immediately. These aren’t normal side effects - they need attention.

For milder changes - like feeling a bit tired or moody - try these steps:

1. Drink more water. Aim for 2.5 liters a day, especially if you’re active or in hot weather.
2. Eat regular meals with balanced carbs, protein, and fat. Skipping meals increases the risk of low blood sugar episodes.
3. Check your blood sugar more often for the first few weeks. If you’re dipping below 4.0 mmol/L, talk to your doctor about adjusting your dose or diet.
4. Get 7-8 hours of sleep. Poor sleep worsens mood swings, and canagliflozin can sometimes disrupt sleep patterns.
5. Move gently. Walking 20 minutes a day helps stabilize blood sugar and boosts endorphins.

Many people find their mood improves after the first 6-8 weeks as their body adjusts. But if it doesn’t? There are alternatives.

Alternatives to canagliflozin

If mood changes stick around, your doctor might switch you to another diabetes medication. Here are the most common options and how they compare:

Metformin is often the first choice for people concerned about mental health. It doesn’t cause dehydration or ketone spikes. GLP-1 agonists like semaglutide are newer but have shown better mood stability in clinical trials. DPP-4 inhibitors are the safest bet if you’ve had bad reactions to other drugs.

What your doctor should be monitoring

When you’re on canagliflozin, your doctor shouldn’t just check your HbA1c and kidney function. They should also ask:

• “How’s your energy level compared to before you started?”
• “Have you felt more anxious or down lately?”
• “Are you sleeping well?”
• “Have you noticed changes in your appetite or interest in things?”

These aren’t optional questions. They’re part of safe prescribing. If your doctor doesn’t bring them up, ask yourself. You’re not being difficult - you’re being smart.

Real stories: What patients have experienced

One woman in Melbourne, 58, started canagliflozin after her HbA1c jumped to 8.9%. Within three weeks, she stopped cooking, canceled plans with friends, and felt like she was moving through fog. Her doctor assumed it was menopause. But when she mentioned the drug, they ran tests. Her sodium was low, her ketones were elevated. They switched her to metformin. Within two weeks, her mood lifted. She started baking again.

A man in Brisbane, 62, with depression and diabetes, was on sertraline when he started canagliflozin. His anxiety spiked. His doctor didn’t connect the dots until he mentioned the new pill. They lowered the canagliflozin dose and added a small amount of electrolyte supplement. His anxiety eased. He’s been stable for eight months.

These aren’t rare cases. They’re signals.

Bottom line: Your mood matters as much as your blood sugar

Canagliflozin is a powerful tool for managing diabetes. But it’s not just a sugar-lowering pill. It’s a metabolic disruptor - and your brain is part of that system.

If you’re taking it and your mood isn’t right, don’t wait. Don’t assume it’s stress or aging. Don’t feel guilty for asking for help. There’s no shame in needing a different medication. Your mental health is just as important as your blood sugar numbers.

Track your symptoms. Talk to your doctor. Try the simple fixes first. And if things don’t improve? There are other options - and you deserve to feel like yourself again.