SGLT2 Inhibitors: How Jardiance, Farxiga, and Invokana Work
If your doctor has recommended a medication like Jardiance, Farxiga, or Invokana for your type 2 diabetes, you may be wondering how these drugs actually work. SGLT2 inhibitors are a newer class of diabetes medication that take a completely different approach to lowering blood sugar — instead of targeting the pancreas or improving insulin sensitivity, they work directly through your kidneys.
This guide explains how SGLT2 inhibitors work, what benefits they offer beyond blood sugar control, what side effects to watch for, and how the three main drugs in this class compare.
How SGLT2 Inhibitors Work
Your kidneys filter about 180 grams of glucose from your blood every day. Under normal circumstances, a protein called SGLT2 (sodium-glucose cotransporter 2) reabsorbs nearly all of that glucose back into your bloodstream before it can be excreted in urine. This is why healthy people do not have sugar in their urine.
SGLT2 inhibitors block this reabsorption process. When SGLT2 is inhibited, the kidneys allow excess glucose to pass into the urine rather than returning it to circulation. The result is that roughly 60–90 grams of glucose are excreted in the urine each day, directly lowering blood sugar levels.
This mechanism is entirely independent of insulin, which means SGLT2 inhibitors work even in patients whose pancreatic beta cells are significantly impaired. They also carry a low risk of hypoglycemia (dangerously low blood sugar) when used without insulin or sulfonylureas, because they only remove excess glucose.
The Three Major SGLT2 Inhibitors
The FDA has approved three SGLT2 inhibitors for type 2 diabetes management in the United States. While all three share the same basic mechanism, they have important differences in their cardiovascular and renal benefit data.
| Drug | Brand Name | FDA-Approved Uses | Typical Monthly Cost |
|---|---|---|---|
| Empagliflozin | Jardiance | T2D, heart failure, CKD | $550–$620 |
| Dapagliflozin | Farxiga | T2D, heart failure, CKD | $530–$600 |
| Canagliflozin | Invokana | T2D, CKD | $500–$580 |
Empagliflozin (Jardiance) was the first SGLT2 inhibitor to demonstrate a significant reduction in cardiovascular death in the landmark EMPA-REG OUTCOME trial. It reduced the risk of cardiovascular death by 38% in patients with established cardiovascular disease. Jardiance is now also approved for heart failure with reduced ejection fraction and chronic kidney disease, regardless of diabetes status.
Dapagliflozin (Farxiga) has the broadest FDA approval of the three, covering type 2 diabetes, heart failure (both reduced and preserved ejection fraction), and chronic kidney disease. The DAPA-HF and DAPA-CKD trials established its benefits in these non-diabetes populations.
Canagliflozin (Invokana) was the first SGLT2 inhibitor approved in the US and demonstrated cardiovascular and renal benefits in the CANVAS and CREDENCE trials. However, it carries a slightly higher risk of lower-limb amputations compared to the other agents, which has affected its prescribing patterns.
Benefits Beyond Blood Sugar Control
One of the most significant developments in diabetes medicine over the past decade has been the discovery that SGLT2 inhibitors provide benefits that extend far beyond glucose lowering. These are now considered among the most important medications in cardiovascular and renal medicine.
Cardiovascular Protection
Multiple large clinical trials have shown that SGLT2 inhibitors reduce the risk of major adverse cardiovascular events (heart attack, stroke, cardiovascular death) in patients with type 2 diabetes who have established cardiovascular disease or are at high cardiovascular risk. The mechanism appears to involve reductions in blood pressure, body weight, and cardiac preload and afterload.
Kidney Protection
SGLT2 inhibitors slow the progression of diabetic kidney disease. The CREDENCE trial showed canagliflozin reduced the risk of kidney failure by 30% in patients with type 2 diabetes and chronic kidney disease. Both empagliflozin and dapagliflozin have since received FDA approval for CKD independent of diabetes.
Heart Failure Benefits
SGLT2 inhibitors reduce hospitalizations for heart failure and improve symptoms in patients with heart failure, even those without diabetes. This is now a first-line recommendation in heart failure guidelines.
Weight Loss and Blood Pressure
Because glucose is excreted in the urine (each gram of glucose carries about 4 calories), patients typically lose 2–4 kg (4–9 lbs) over the first year. SGLT2 inhibitors also reduce systolic blood pressure by 3–5 mmHg on average, providing an additional cardiovascular benefit.
Side Effects and Risks
Genital Yeast Infections and UTIs
The most common side effect of SGLT2 inhibitors is an increased risk of genital mycotic infections (yeast infections). Because glucose is present in the urine, it creates a favorable environment for fungal growth. Women are affected more frequently than men. Urinary tract infections are also more common, though the absolute risk increase is modest.
Diabetic Ketoacidosis (DKA)
A rare but serious risk is euglycemic diabetic ketoacidosis — a condition where ketoacids build up in the blood even when blood sugar is not dramatically elevated. This risk is higher during periods of illness, fasting, or surgery. Patients should hold their SGLT2 inhibitor at least 3 days before any planned surgery.
Dehydration and Low Blood Pressure
The glucose-driven diuresis can cause mild dehydration and a drop in blood pressure, particularly in elderly patients or those taking diuretics. Dose adjustment or temporary discontinuation may be needed during illness with poor fluid intake.
Lower-Limb Amputation Risk (Canagliflozin)
Canagliflozin carries an FDA black box warning for an increased risk of lower-limb amputations, primarily at the level of the toe or metatarsal. Patients with peripheral vascular disease or prior amputations should generally avoid this agent.
Who Is a Good Candidate for SGLT2 Inhibitors?
SGLT2 inhibitors are particularly well-suited for patients who have:
- Type 2 diabetes with established cardiovascular disease or high cardiovascular risk — the cardiovascular mortality benefit is most pronounced in this group
- Type 2 diabetes with chronic kidney disease — SGLT2 inhibitors are now recommended by major nephrology guidelines as kidney-protective agents
- Heart failure — regardless of diabetes status, SGLT2 inhibitors reduce hospitalizations and improve outcomes
- Obesity — the modest weight loss effect is a meaningful benefit for overweight patients
- Hypertension — the blood pressure-lowering effect provides additional benefit
They are generally not recommended for patients with type 1 diabetes (due to DKA risk), severe kidney impairment (eGFR below 20–25), or recurrent genital infections.
How SGLT2 Inhibitors Compare to Other Diabetes Medications
| Feature | SGLT2 Inhibitors | GLP-1 Agonists | Metformin | DPP-4 Inhibitors |
|---|---|---|---|---|
| A1c reduction | 0.5–1.0% | 1.0–1.5% | 1.0–1.5% | 0.5–0.8% |
| Weight effect | Loss (2–4 kg) | Loss (3–6 kg) | Neutral/slight loss | Neutral |
| Hypoglycemia risk | Low | Low | Very low | Very low |
| Cardiovascular benefit | Strong (proven) | Strong (proven) | Moderate | Neutral |
| Kidney protection | Strong (proven) | Moderate | Moderate | Neutral |
| Cost | High ($500+/mo) | High ($900+/mo) | Very low ($4–$15/mo) | Moderate ($200–$400/mo) |
| Route | Oral | Injection (most) | Oral | Oral |
For a comprehensive overview of all diabetes medication classes, see our Type 2 Diabetes Medications Guide.
Cost and Insurance Coverage
SGLT2 inhibitors are brand-name medications with no generic alternatives currently available in the US, making them among the more expensive diabetes drugs. Without insurance, monthly costs range from $500 to $620. Most major insurance plans cover at least one SGLT2 inhibitor, though prior authorization is often required.
Manufacturer savings programs can significantly reduce out-of-pocket costs:
- Jardiance: Boehringer Ingelheim/Eli Lilly offer a savings card that may reduce cost to $10/month for eligible commercially insured patients
- Farxiga: AstraZeneca offers a savings card for eligible patients
- Invokana: Janssen offers a patient assistance program
Medicare Part D covers SGLT2 inhibitors, but coverage varies by plan formulary tier.
Key Takeaways
SGLT2 inhibitors represent a major advance in type 2 diabetes treatment. By working through the kidneys rather than the pancreas, they lower blood sugar through a mechanism that is independent of insulin and carries a low hypoglycemia risk. More importantly, they have demonstrated benefits for the heart and kidneys that go well beyond glucose control — benefits that have made them a cornerstone of treatment for patients with cardiovascular disease, heart failure, and chronic kidney disease.
If you are managing type 2 diabetes and have not discussed SGLT2 inhibitors with your doctor, it is worth asking whether one of these medications might be appropriate for your situation.
This article is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider before starting, stopping, or changing any medication.
About the Author
RxGuide Editorial Team, PharmD, RPh
Clinical Pharmacist & Medical Writer
The RxGuide editorial team is composed of licensed pharmacists and clinical medical writers with expertise in pharmacology, drug safety, and patient education. All clinical content is reviewed against current FDA labeling, peer-reviewed literature, and established clinical guidelines before publication.
