SGLT2 Inhibitors (Class Overview)

What This Medicine Does

SGLT2 inhibitors (sometimes called "flozins") work in a unique way - they help your kidneys remove excess sugar from your body through your urine.

How it works:

1. Normally: Your kidneys filter sugar from blood but reabsorb almost all of it back into your body
2. With this medicine: It blocks that reabsorption, so excess sugar is removed in your urine
3. The result: Lower blood sugar without needing extra insulin

Bonus benefits discovered:

• Helps protect your heart (reduces heart failure hospitalizations)
• Slows kidney disease progression
• May lead to modest weight loss
• Can slightly lower blood pressure

---

What to Expect: A Timeline

Day 1-3: Getting Started

You'll notice:

• Increased urination - This is expected and shows the medicine is working
• Mild thirst - Drink plenty of water

This effect decreases over time as your body adjusts.

Week 1-2: Settling In

• Blood sugar levels start improving
• Urination frequency normalizes
• You may notice slight weight loss (water weight initially)

Month 1-3: Ongoing Benefits

• Improved HbA1c levels
• Possible continued modest weight loss
• Blood pressure may decrease slightly

Long-Term: Protection

• Heart benefits accumulate over months to years
• Kidney protection continues as long as you take the medicine
• Cardiovascular risk reduction

---

Common Things You Might Notice

Increased Urination (Very Common - Especially at First)

• Why: The medicine causes sugar to leave in your urine, which pulls water with it
• When: Most noticeable in the first week
• What to do: Drink plenty of water, plan bathroom access
• Good news: This effect lessens over time

Genital & Urinary Issues

• Yeast infections - More common in women; can also affect men
• Urinary tract infections - Slightly increased risk
• What to watch: Burning, itching, unusual discharge, pain with urination

Other Common Effects

• Mild thirst or dry mouth
• Slight nausea (rare)
• Weakness or fatigue (especially if also taking diuretics)

---

Sick Day Rules: Very Important!

SGLT2 inhibitors can increase your risk of a dangerous condition called euglycemic DKA (diabetic ketoacidosis with normal blood sugar). This is rare but serious.

When to Temporarily Stop This Medicine

STOP taking this medicine and contact your doctor if:

• You're vomiting more than twice in 6 hours
• You have diarrhea for more than 24 hours
• You can't eat or drink normally
• You have a fever above 101°F (38.3°C)
• You're having surgery (stop 3-4 days before, as directed by your doctor)
• You're having a medical test with contrast dye
• You're doing intense physical activity or fasting

What is Euglycemic DKA?

Unlike typical DKA, your blood sugar may be normal or only slightly elevated even though your body is producing ketones. This can fool you into thinking everything is fine.

Symptoms to watch for:

• Nausea, vomiting, abdominal pain
• Rapid, deep breathing
• Confusion or difficulty concentrating
• fruity breath odor
• Unusual tiredness

If you have these symptoms, seek immediate care and mention you take an SGLT2 inhibitor.

---

When to Call Your Doctor

Seek Immediate Care For:

• Severe abdominal pain, nausea, or vomiting
• Rapid breathing or shortness of breath
• Confusion, difficulty concentrating
• fruity breath odor
• Severe genital pain, swelling, or redness

Contact Your Doctor Soon For:

• Symptoms of yeast infection (itching, discharge, redness)
• Burning or pain with urination
• Fever or signs of infection
• Significant weight loss or weakness
• Dizziness or fainting (could indicate dehydration)

---

Hygiene & Prevention Tips

Preventing Genital Infections

1. Stay clean and dry - Wash and dry the genital area thoroughly daily
2. Wear breathable clothing - Cotton underwear, loose-fitting clothes
3. Change quickly - Don't stay in wet swimsuits or sweaty clothes
4. Urinate after sex - Helps prevent UTIs
5. Stay hydrated - Drink plenty of water to flush bacteria
6. Consider probiotics - May help maintain healthy bacteria balance

Preventing UTIs

1. Drink water - Aim for 6-8 glasses daily
2. Don't hold it - Urinate when you feel the urge
3. Wipe front to back - Helps prevent bacteria spread
4. Shower, don't soak - Avoid long baths if prone to UTIs

---

Practical Daily Tips

1. Take in the morning - Most people take it with breakfast; taking earlier in the day means more bathroom visits happen while you're awake

2. Stay hydrated - Especially important when starting this medicine

3. Wear light pads - For women, some mild urine leakage is possible initially

4. Plan bathroom access - Especially in the first week, be prepared for more frequent trips

5. Track your symptoms - Note any infections, side effects, or changes to discuss with your doctor

6. Have a sick day plan - Know when to stop the medicine and when to call for help

---

Food & Medicine Interactions

Diuretics ("Water Pills")

• Interaction: Increased risk of dehydration and low blood pressure
• What to do: Monitor for dizziness; your doctor may adjust doses

Blood Pressure Medicines

• Interaction: May further lower blood pressure
• What to do: Monitor for dizziness, especially when standing up quickly

Insulin or Sulfonylureas

• Interaction: May need dose reduction to avoid low blood sugar
• What to do: Your doctor may adjust these medicines when starting SGLT2 inhibitors

---

For Healthcare Professionals

Clinical Information

Pharmacology & Mechanism

SGLT2 inhibitors block the sodium-glucose cotransporter 2 (SGLT2) in the proximal tubule, inhibiting renal glucose reabsorption and causing glucosuria. This results in:

• Reduced blood glucose independent of insulin secretion
• Osmotic diuresis (natriuresis and calciuresis)
• Modest blood pressure reduction
• Weight loss through calorie loss
• Potential hemodynamic benefits (reduced preload and afterload)

Available Agents & Dosing

Monitoring Requirements

Baseline:

• eGFR, serum creatinine
• Potassium
• Urinalysis (if history of GU infections)
• Ketone testing capability if at risk for DKA

Follow-up:

• Renal function (eGFR) periodically
• Volume status assessment
• Signs/symptoms of GU infections at each visit
• Ketones during acute illness

Expected Lab Changes:

• Small eGFR dip (~3-5 mL/min/1.73m²) is expected initially
• Small hematocrit increase (due to hem concentration)
• Small phosphate increase

Contraindications & Warnings

Boxed Warnings:

• None class-wide (post-marketing warnings for DKA, severe UTIs)

Contraindications:

• Severe renal impairment (varies by agent, see table above)
• Dialysis patients
• Type 1 diabetes mellitus
• History of serious hypersensitivity

Warnings & Precautions:

• Ketoacidosis - Euglycemic DKA reported; assess for ketones in metabolic acidosis without severe hyperglycemia
• Volume depletion - Can cause hypotension, especially in elderly, on diuretics, or with low BP
• Urogenital infections - Increased risk of mycotic and bacterial infections
• Necrotizing fasciitis of perineum (Fournier's gangrene) - Rare but serious; prompt treatment required
• Lower limb amputation - Canagliflozin specifically; monitor for ulcers/pain
• Acute kidney injury - Risk increased with volume depletion

Drug Interactions

Special Populations

Pregnancy: Category C - avoid, especially second and third trimesters

Breastfeeding: Not recommended

Geriatric: Increased risk of volume depletion, UTIs, falls from hypotension

Renal Impairment: Dose adjustment or discontinuation required based on eGFR

Hepatic Impairment: No dose adjustment needed for mild-moderate; avoid severe hepatic impairment for canagliflozin

Sick Day Rules for Patients

TEMPORARILY DISCONTINUE if:

• Acute illness causing significant reduced oral intake
• Vomiting ＞2 episodes in 6 hours or diarrhea ＞24 hours
• Fever ＞101°F (38.3°C)
• Scheduled surgery or procedures with contrast (discontinue 3-4 days prior)
• Extreme physical exertion or fasting

RESTART when:

• Oral intake resumes and illness resolves
• 48-72 hours after surgery/procedure
• Clinician approves

Efficacy Data

Glycemic Control:

• HbA1c reduction: 0.7-1.2% as monotherapy or add-on

Cardiovascular Outcomes:

• EMPA-REG OUTCOME: 14% reduction in CV death, 35% reduction in HF hospitalization
• DECLARE-TIMI 58: 27% reduction in HF hospitalization
• DAPA-HF: 30% reduction in CV death/HF hospitalization (including non-diabetics)

Kidney Outcomes:

• DAPA-CKD: 39% reduction in sustained eGFR decline, ESKD, or renal/CV death
• CREDENCE: 34% reduction in ESKD or renal death

Weight Loss:

• Modest: 2-3 kg average loss over 6-12 months

---

Medical Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider before starting, stopping, or changing any medication.