Synjardy is a fixed-dose combination tablet that pairs empagliflozin (the SGLT2 inhibitor sold separately as Jardiance) with metformin in a single pill, typically taken twice daily with meals. It is approved for adults with type 2 diabetes who need more than one medication to reach their A1C goal, offering combined glucose lowering of around 1.5 to 2.5 percent along with cardiovascular and kidney benefits from the empagliflozin component. An extended-release version, Synjardy XR, allows once-daily dosing.
What Synjardy Contains
Synjardy is manufactured by Boehringer Ingelheim and Eli Lilly. Each tablet contains two active ingredients with complementary mechanisms of action:
- Empagliflozin — a sodium-glucose cotransporter-2 (SGLT2) inhibitor that blocks glucose reabsorption in the proximal tubule of the kidney, causing excess glucose to be excreted in the urine. It lowers blood sugar independently of insulin, reduces body weight by 2 to 4 kg, lowers systolic blood pressure by 3 to 5 mmHg, and protects the heart and kidneys.
- Metformin hydrochloride — a biguanide that reduces hepatic glucose production, modestly improves peripheral insulin sensitivity, and slows intestinal glucose absorption. Metformin has been the first-line diabetes medication for over 25 years.
Because the two drugs work through entirely different mechanisms, their effects add together rather than overlap, making the combination more potent than either drug alone at the same individual doses.
Available Strengths and Dosing
Synjardy comes in four strengths designed to allow flexible titration:
| Strength (mg) | Empagliflozin | Metformin | Typical Daily Total |
|---|---|---|---|
| 5/500 | 5 mg | 500 mg | 10/1000 mg (one tablet BID) |
| 5/1000 | 5 mg | 1,000 mg | 10/2000 mg (one tablet BID) |
| 12.5/500 | 12.5 mg | 500 mg | 25/1000 mg (one tablet BID) |
| 12.5/1000 | 12.5 mg | 1,000 mg | 25/2000 mg (one tablet BID) |
Standard Synjardy is taken twice daily with meals to reduce stomach upset from the metformin component. The maximum daily dose is empagliflozin 25 mg plus metformin 2,000 mg.
Synjardy XR is taken once daily with the evening meal. Strengths include 5/1000, 10/1000, 12.5/1000, 25/1000, and 25/2000 mg. The extended-release metformin reduces gastrointestinal side effects for many patients and improves adherence with once-daily dosing.
Who Synjardy Is For
Synjardy is approved for adults with type 2 diabetes as an adjunct to diet and exercise. It is most commonly prescribed when:
- A1C remains above goal (typically above 7.0 percent) despite metformin monotherapy
- A patient is already taking empagliflozin and metformin as separate prescriptions and wants to simplify
- Cardiovascular disease, heart failure, or chronic kidney disease is present and an SGLT2 inhibitor is recommended by the treatment guidelines
- Weight loss and blood pressure benefits are desired alongside glycemic control
It is not approved for type 1 diabetes, diabetic ketoacidosis, or use in pregnancy.
How Well Synjardy Works
Clinical trial data from the individual components and head-to-head combination studies show:
- A1C reduction: approximately 1.5 to 2.5 percent from baseline when started in patients with poorly controlled type 2 diabetes. Higher starting A1C predicts larger absolute reductions.
- Weight loss: 2 to 4 kg over 24 to 52 weeks, driven mainly by empagliflozin’s caloric loss through urinary glucose excretion (around 70 to 80 grams of glucose, or 280 to 320 calories per day).
- Blood pressure: systolic reduction of 3 to 5 mmHg.
- Cardiovascular benefit: the EMPA-REG OUTCOME trial showed empagliflozin reduced cardiovascular death by 38 percent in patients with type 2 diabetes and established cardiovascular disease.
- Kidney benefit: the EMPA-KIDNEY trial demonstrated a 28 percent reduction in kidney disease progression in patients with chronic kidney disease, regardless of diabetes status.
For context on what a1c reduction means clinically, see our explainer on A1C levels and targets.
Side Effects
Synjardy’s side effect profile is the combination of empagliflozin’s and metformin’s individual profiles.
| Side Effect | Source | Frequency |
|---|---|---|
| Genital yeast infections | Empagliflozin | 4 to 12 percent |
| Urinary tract infections | Empagliflozin | 7 to 9 percent |
| Nausea, diarrhea, abdominal cramps | Metformin | 10 to 25 percent (often transient) |
| Increased urination, thirst | Empagliflozin | 3 to 5 percent |
| Metallic taste | Metformin | 3 percent |
| Vitamin B12 deficiency (long-term) | Metformin | 5 to 10 percent at 5+ years |
| Euglycemic diabetic ketoacidosis | Empagliflozin | Rare (less than 0.1 percent) |
| Lactic acidosis | Metformin | Very rare (3 to 10 per 100,000 patient-years) |
| Volume depletion, hypotension | Empagliflozin | 1 to 3 percent |
| Acute kidney injury | Both | Rare |
Most gastrointestinal side effects from metformin improve within 2 to 4 weeks. Genital infections can usually be treated with a short course of topical antifungal therapy and good hygiene; recurrent infections may warrant a different combination.
Serious Risks and Contraindications
- eGFR less than 30 mL/min/1.73 m squared: contraindicated due to metformin lactic acidosis risk.
- eGFR 30 to 45: metformin requires dose adjustment; Synjardy may be continued with caution but not initiated.
- Active diabetic ketoacidosis: stop immediately.
- Severe hepatic impairment, acute alcohol intoxication, or chronic alcoholism: increase lactic acidosis risk.
- Iodinated contrast imaging: hold Synjardy 48 hours before and after to prevent contrast-induced kidney injury and lactic acidosis.
- Surgery and prolonged fasting: hold for 3 to 4 days perioperatively (the SGLT2 inhibitor component carries ketoacidosis risk during fasting and stress).
- Recurrent UTIs, prior diabetic foot ulcers, or peripheral arterial disease: use cautiously.
Drug Interactions
Notable interactions include:
- Loop and thiazide diuretics: additive volume depletion — monitor blood pressure and renal function.
- Insulin and sulfonylureas: increased hypoglycemia risk when combined; doses of these medications may need reduction.
- Cationic drugs (cimetidine, dolutegravir, ranolazine): can raise metformin levels.
- Iodinated contrast: see above.
- Alcohol: increases lactic acidosis and hypoglycemia risk.
Cost and Insurance
Synjardy is brand-only in the United States. Average wholesale price runs roughly $600 to $800 per 30-day supply. With commercial insurance, copays typically fall between $30 and $80 per month, and Boehringer Ingelheim’s manufacturer savings card can reduce eligible patients’ out-of-pocket cost to as little as $10 per month for up to 24 months. Medicare and Medicaid patients are not eligible for the manufacturer savings program but may qualify for patient assistance based on income. Many patients find it cheaper to take generic metformin plus brand Jardiance separately if the combination is not on formulary.
Storage and Handling
- Store at controlled room temperature, 68 to 77 degrees F (20 to 25 degrees C).
- Keep in original blister pack until use.
- Protect from moisture and heat.
- Do not crush, split, or chew Synjardy XR tablets — extended-release coating must remain intact.
How Synjardy Fits Modern Type 2 Diabetes Care
ADA Standards of Care 2024 recommend metformin plus an SGLT2 inhibitor for patients with type 2 diabetes and high cardiovascular risk, heart failure, or chronic kidney disease. Synjardy delivers both in one tablet, which may improve adherence. For patients without these comorbidities, the combination is still reasonable when monotherapy fails, but the choice between SGLT2 inhibitor combinations (Synjardy vs Xigduo XR vs Invokamet) often depends on insurance formulary and prior experience.
Comparison to Three-Drug Combination Trijardy XR
Patients needing additional A1C lowering beyond Synjardy may step up to Trijardy XR, which adds linagliptin (a DPP-4 inhibitor) to the same empagliflozin-metformin base. Combined A1C reduction can exceed 2.5 percent with Trijardy XR. The DPP-4 component is generally well tolerated and adds further glucose-dependent insulin release.
Prediabetes Considerations
Synjardy is not approved for prediabetes. For people with prediabetes, metformin alone is occasionally used off-label and is recommended by ADA for high-risk patients (BMI 35+, age under 60, prior gestational diabetes), but SGLT2 inhibitors are reserved for type 2 diabetes. Lifestyle modification — sustainable diet change, physical activity, and weight loss — remains the foundation. See our guide on whether prediabetes is reversible for context.
The Bottom Line
Synjardy combines empagliflozin and metformin in a single twice-daily tablet (or once-daily Synjardy XR) for adults with type 2 diabetes. Four strengths allow flexible titration, with combined A1C reduction of 1.5 to 2.5 percent, modest weight loss, blood pressure improvement, and cardiovascular and kidney protection from the empagliflozin component. The main side effects are genital yeast infections, urinary tract infections, and gastrointestinal symptoms from metformin. Synjardy is contraindicated below an eGFR of 30 and should be held around contrast imaging and surgery. Cost is similar to brand Jardiance alone, and manufacturer copay cards make it accessible for most commercially insured patients. Talk to your clinician about whether combining your current pills into Synjardy makes sense for adherence and cost.
