What Are SGLT-2 Inhibitors?
SGLT-2 inhibitors are a class of medications that lower blood sugar by causing your kidneys to remove excess glucose (sugar) from the body through urine, rather than reabsorbing it back into the bloodstream. Two medications used in this class at Healthspan are canagliflozin (Invokana) and bexagliflozin (Brenzavvy). Originally developed for type 2 diabetes, SGLT-2 inhibitors have since shown remarkable benefits for the heart, kidneys, and metabolic health — making them one of the most exciting classes of medications in modern medicine for longevity and cardiometabolic health.
How Do They Work?
Your kidneys normally filter glucose from the blood and then reabsorb almost all of it back into the body. SGLT-2 inhibitors block a transporter protein (SGLT-2) in the kidney's filtering tubes, preventing glucose reabsorption. This means excess glucose leaves your body through urine, lowering blood sugar levels without requiring insulin. Additional effects include reducing blood pressure, promoting mild weight loss, and reducing sodium retention — which together benefit the heart and kidneys.
Benefits
- Blood sugar control — effectively lowers blood sugar and A1C without causing low blood sugar on its own
- Weight loss support — the calorie loss through glucose in urine results in modest but meaningful weight reduction (typically 2–4 kg)
- Blood pressure reduction — lowers blood pressure through fluid and sodium excretion
- Heart protection — dramatically proven in multiple large clinical trials to reduce heart failure hospitalizations and cardiovascular death, including in people both with and without diabetes
- Kidney protection — slows progression of chronic kidney disease independent of blood sugar control
- Reduces visceral fat — particularly effective at reducing fat around the organs
- Metabolic longevity benefits — improved insulin sensitivity, reduced inflammation, and caloric restriction-mimicking effects
- Uric acid reduction — may reduce uric acid levels, which is relevant for gout and metabolic health
How to Take SGLT-2 Inhibitors
- Form: Oral tablet, taken by mouth once daily
- Canagliflozin dose: Typically 100 mg once daily; may be increased to 300 mg based on your provider's guidance
- Bexagliflozin dose: Typically 20 mg once daily
- Timing: Take in the morning before your first meal of the day
- Hydration: Drink adequate water throughout the day — these medications cause your kidneys to excrete more fluid
- Consistency: Take at the same time each day
What to Expect
- Within days to 1 week: Blood sugar levels begin to fall as glucose is excreted; some people notice mild diuresis (increased urination) early on
- 2–4 weeks: Blood pressure reductions are often noticeable; early weight loss begins
- 3–6 months: Sustained improvements in blood sugar, weight, and blood pressure; metabolic markers improve
- Ongoing: Cardiovascular and kidney protection benefits accumulate with long-term use
Side Effects
SGLT-2 inhibitors are generally well tolerated. Possible side effects include:
- Genital yeast infections — the most common side effect; excess sugar in urine promotes fungal growth in the genital area (more common in women); good hygiene helps minimize this
- Urinary tract infections (UTIs) — somewhat increased risk; stay well hydrated and maintain good hygiene
- Increased urination — especially in the first few weeks
- Dehydration — important to drink adequate water; avoid prolonged fasting or excessive heat without hydration
- Low blood pressure — particularly if you are already on blood pressure medications or are prone to dehydration
- Mild dizziness — related to fluid shifts, especially early in treatment
Important — Diabetic Ketoacidosis (DKA): A rare but serious side effect where the body produces excess ketones. Symptoms include nausea, vomiting, abdominal pain, difficulty breathing, and confusion. Stop the medication and seek immediate medical care if you experience these symptoms. This is more likely in people with type 1 diabetes or those undergoing significant fasting/illness.
Who Should Not Take SGLT-2 Inhibitors?
- People with significant kidney disease (eGFR below 30 for most indications)
- People with a history of recurrent genital yeast infections or UTIs
- People on dialysis
- Women who are pregnant or breastfeeding
- Anyone with type 1 diabetes (use is not standard and requires specialist supervision)
- Anyone with a known allergy to canagliflozin or bexagliflozin
Storage Instructions
- Store at room temperature (59°F–77°F / 15°C–25°C)
- Keep away from moisture and heat
- Keep out of reach of children
Frequently Asked Questions
Will SGLT-2 inhibitors cause low blood sugar?
On their own, SGLT-2 inhibitors rarely cause low blood sugar because they work independent of insulin. However, if combined with insulin or certain other diabetes medications, low blood sugar risk increases. Always inform your provider of all medications you are taking.
Why is there sugar in my urine — is that a problem?
This is the intended effect! SGLT-2 inhibitors work specifically by causing your kidneys to excrete glucose in urine, lowering blood sugar levels. It is not harmful — it is how the medication works.
How does an SGLT-2 inhibitor protect the heart?
These medications reduce pressure and volume load on the heart, lower blood pressure, reduce inflammation, and have direct beneficial effects on heart muscle cells. Multiple large trials have proven their ability to reduce heart failure hospitalizations and death, making them a cornerstone of modern cardiovascular medicine.
Can I use SGLT-2 inhibitors if I don't have diabetes?
Yes — canagliflozin and bexagliflozin are increasingly used in people without diabetes for their cardiovascular and kidney-protective effects, as well as for their metabolic longevity benefits. Your provider will assess whether this is appropriate for you.
How do I prevent yeast infections while taking SGLT-2 inhibitors?
Good genital hygiene is key. Keep the area clean and dry, wear breathable cotton underwear, and stay well hydrated. If you develop a yeast infection, your provider can recommend appropriate treatment.