Short answer: In the label's 24-week trial of empagliflozin added to metformin and a sulfonylurea, side effects seen in at least 5% and more often than on placebo were low blood sugar (15.6% on 10 mg vs 9.8%), urinary tract infection (9.4% vs 6.7%) and stuffy or runny nose (8.0% vs 4.9%). Genital yeast infections were also more common. Synjardy has a boxed warning for lactic acidosis from its metformin part.
What Synjardy is approved for: Synjardy combines empagliflozin, an SGLT2 inhibitor, with metformin, a biguanide. Along with diet and exercise it is approved to improve blood sugar control in adults and children 10 years and older with type 2 diabetes; Synjardy XR is for adults (section 1). In adults with type 2 diabetes the empagliflozin part also lowers the risk of heart death in established heart disease, heart death and heart failure hospital stays in heart failure, and kidney decline in chronic kidney disease. It is not recommended for type 1 diabetes.
Source
SYNJARDY (empagliflozin and metformin hydrochloride) tablets and SYNJARDY XR (empagliflozin and metformin hydrochloride extended-release) tablets, for oral use, prescribing information and Medication Guide. Boehringer Ingelheim Pharmaceuticals. DailyMed, version published August 27, 2026. DailyMed setid 0fdd0255-0055-65f3-b2c0-db8fbb87beae
WARNING: LACTIC ACIDOSIS
Cases of metformin-associated lactic acidosis reported after approval have resulted in death, low body temperature, low blood pressure and slow heart rhythms that resist treatment. It often starts subtly, with only vague symptoms such as feeling unwell, muscle aches, trouble breathing, sleepiness and abdominal pain. It was marked by blood lactate above 5 mmol/L, anion gap acidosis without ketones, a raised lactate to pyruvate ratio, and metformin levels generally above 5 mcg/mL. Risk factors include kidney impairment, certain drugs (for example carbonic anhydrase inhibitors such as topiramate), age 65 or older, a radiology study with contrast, surgery and other procedures, low-oxygen states such as acute heart failure, heavy alcohol use, liver impairment and mitochondrial diseases. If it is suspected, Synjardy is stopped immediately and supportive care is started in a hospital; prompt hemodialysis is recommended.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Synjardy.
| Adverse reaction | Placebo (n=225) | Empagliflozin 10 mg (n=224) | Empagliflozin 25 mg (n=217) |
|---|---|---|---|
| Hypoglycemia | 9.8% | 15.6% | 12.9% |
| Urinary tract infection | 6.7% | 9.4% | 6.9% |
| Nasopharyngitis | 4.9% | 8.0% | 6.0% |
Percent of patients. Nasopharyngitis means a stuffy or runny nose with sore throat.
| Adverse reaction | Placebo (N=995) | Empagliflozin 10 mg (N=999) | Empagliflozin 25 mg (N=977) |
|---|---|---|---|
| Urinary tract infection | 7.6% | 9.3% | 7.6% |
| Female genital mycotic infections | 1.5% | 5.4% | 6.4% |
| Upper respiratory tract infection | 3.8% | 3.1% | 4.0% |
| Increased urination | 1.0% | 3.4% | 3.2% |
| Dyslipidemia | 3.4% | 3.9% | 2.9% |
| Arthralgia | 2.2% | 2.4% | 2.3% |
| Male genital mycotic infections | 0.4% | 3.1% | 1.6% |
| Nausea | 1.4% | 2.3% | 1.1% |
Pool of five placebo-controlled trials of empagliflozin alone or added to other medicines, excluding low blood sugar. Female and male genital yeast infection rates use the number of women or men in each group.
| Trial and measure | Placebo | Empagliflozin 10 mg | Empagliflozin 25 mg |
|---|---|---|---|
| With metformin HCl (24 weeks), n = 206 / 217 / 214: Overall (%) | 0.5 | 1.8 | 1.4 |
| With metformin HCl + sulfonylurea (24 weeks), n = 225 / 224 / 217: Overall (%) | 8.4 | 16.1 | 11.5 |
| With basal insulin +/- metformin HCl (18 weeks), n = 170 / 169 / 155: Overall (%) | 20.6 | 19.5 | 28.4 |
| With basal insulin +/- metformin HCl: Severe (%) | 0 | 0 | 1.3 |
| With MDI insulin +/- metformin HCl (18 weeks), n = 188 / 186 / 189: Overall (%) | 37.2 | 39.8 | 41.3 |
| With MDI insulin +/- metformin HCl: Severe (%) | 0.5 | 0.5 | 0.5 |
Overall means a glucose of 70 mg/dL or less; severe means needing help from someone else. Only the trials that included metformin as background are shown; the label also lists monotherapy and pioglitazone trials.
Across 3,456 adults on empagliflozin with metformin for 16 to 24 weeks, stopping for side effects was 3.0% on placebo, 2.8% on empagliflozin 10 mg and 2.9% on 25 mg.
Metformin: the most common side effects when starting it are diarrhea, nausea or vomiting, gas, abdominal discomfort, indigestion, weakness and headache. When extended-release metformin was added to glyburide, low blood sugar was 13.7% vs 4.9%, diarrhea 12.5% vs 5.6% and nausea 6.7% vs 4.2%.
Urinary tract infections were more common in women: 16.6% on placebo, 18.4% on empagliflozin 10 mg and 17.0% on 25 mg, vs 3.2%, 3.6% and 4.1% in men.
Fluid-loss side effects such as low blood pressure or fainting: 0.3% on placebo, 0.5% on 10 mg and 0.3% on 25 mg. Thirst: 0%, 1.7% and 1.5%.
Lower limb amputation across four empagliflozin outcome trials: 4.3 vs 5.0 events per 1,000 patient-years on placebo vs empagliflozin.
In children 10 to 17 years, blood sugar below 54 mg/dL occurred in 19.2% on empagliflozin vs 7.5% on placebo, with no severe events.
Reported after approval, with frequency unknown: constipation; Fournier's gangrene, urosepsis and kidney infection; ketoacidosis; acute kidney injury; angioedema and skin reactions; and, for metformin, liver injury.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Lactic acidosis. The boxed-warning risk. Synjardy is not used with an eGFR below 30, and starting it is not recommended below 45. eGFR is checked before starting and at least yearly. It is stopped around some iodinated contrast scans, paused while food and fluids are restricted, stopped in shock, heart attack, sepsis or acute heart failure with low oxygen, and avoided with liver disease.
Ketoacidosis. Ketoacidosis, which can be fatal, can happen even with blood sugar below 250 mg/dL. It is checked for whatever the blood sugar, and Synjardy is stopped if it is suspected. It is not recommended in type 1 diabetes.
Volume depletion. Empagliflozin can cause fluid loss and low blood pressure, especially with kidney problems, in older people or with loop diuretics. Fluid status is checked before starting.
Urinary and genital infections, including Fournier's gangrene. Serious urinary infections, kidney infections, genital yeast infections and a rare serious genital-area infection (Fournier's gangrene) have been reported. Pain, redness or swelling in the genital area with fever is checked right away.
Low blood sugar. Adults on insulin or a medicine that makes the body release insulin may have more low blood sugar, and a lower dose of those may be considered. In children 10 and older, the risk was higher regardless of insulin.
Lower limb amputation. People are watched for infections or ulcers of the legs and feet, which are treated.
Allergic reactions. Serious allergic reactions such as angioedema have occurred with empagliflozin. Synjardy is stopped if one occurs.
Vitamin B12 deficiency. Metformin may lower vitamin B12. Blood counts are measured yearly and vitamin B12 every 2 to 3 years.
From the Medication Guide that comes with Synjardy:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.