Short answer: In the label's 52-week trial of empagliflozin, linagliptin and metformin taken together, the most common side effects were upper respiratory infection (10.3% on the 10 mg empagliflozin combination and 8.0% on 25 mg), urinary tract infection (9.6% and 10.2%) and stuffy or runny nose (8.1% and 5.8%). This trial had no placebo group. Trijardy XR has a boxed warning for lactic acidosis from its metformin part.
What Trijardy XR is approved for: Trijardy XR combines three medicines in one tablet: empagliflozin (an SGLT2 inhibitor), linagliptin (a DPP-4 inhibitor) and extended-release metformin (a biguanide). Along with diet and exercise it is approved to improve blood sugar control in adults with type 2 diabetes, and its empagliflozin part lowers the risk of heart death in adults with type 2 diabetes and established heart disease (section 1). It is not recommended for type 1 diabetes, and it has not been studied in people who have had pancreatitis.
Source
TRIJARDY XR (empagliflozin, linagliptin, and metformin hydrochloride extended-release tablets), for oral use, prescribing information and Medication Guide. Boehringer Ingelheim Pharmaceuticals. DailyMed, version published August 25, 2026. DailyMed setid 71873567-9594-452a-bb92-34a129adecac
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, Trijardy XR 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 Trijardy XR.
| Adverse reaction | Empagliflozin 10 mg + Linagliptin 5 mg + Metformin HCl (%) n=136 | Empagliflozin 25 mg + Linagliptin 5 mg + Metformin HCl (%) n=137 |
|---|---|---|
| Upper respiratory tract infection | 10.3 | 8.0 |
| Urinary tract infection | 9.6 | 10.2 |
| Nasopharyngitis | 8.1 | 5.8 |
| Diarrhea | 6.6 | 2.2 |
| Constipation | 5.1 | 5.8 |
| Headache | 5.1 | 5.1 |
| Gastroenteritis | 2.9 | 5.8 |
Percent of patients; there was no placebo group. Urinary tract infection is a predefined grouping that includes asymptomatic bacteriuria and cystitis. Nasopharyngitis means a stuffy or runny nose with sore throat; gastroenteritis is inflammation of the stomach and intestine.
Low blood sugar below 54 mg/dL was 0.7% on each combination in the 52-week trial, and there was no severe low blood sugar (needing help from someone else).
Empagliflozin vs placebo (10 mg, 25 mg, placebo): urinary tract infection 9.3%, 7.6% and 7.6%; female genital yeast infections 5.4%, 6.4% and 1.5%; increased urination 3.4%, 3.2% and 1.0%; male genital yeast infections 3.1%, 1.6% and 0.4%; thirst 1.7%, 1.5% and 0%.
Linagliptin 5 mg vs placebo: stuffy or runny nose 7.0% vs 6.1%, diarrhea 3.3% vs 3.0%, and cough 2.1% vs 1.4%. Pancreatitis in the linagliptin program was 15.2 cases per 10,000 patient-years vs 3.7 on comparator.
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%.
Fluid-loss events (low blood pressure and fainting) were reported in 3 patients (1.1%) on the three-medicine combination. In metformin trials of 29 weeks, vitamin B12 fell below normal in about 7%.
Reported after approval, with frequency unknown: acute pancreatitis including fatal cases; mouth ulcers; allergic reactions including anaphylaxis and angioedema; Fournier's gangrene, urosepsis and kidney infection; ketoacidosis; rhabdomyolysis; severe joint pain; acute kidney injury; bullous pemphigoid; rash or hives; and 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. Trijardy XR is not used with an eGFR below 30. eGFR is checked before starting and at least yearly, more often in older people. 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, avoided with liver disease, and not recommended with mitochondrial diseases such as MELAS and MIDD.
Diabetic ketoacidosis in type 1 diabetes and other ketoacidosis. Ketoacidosis, which can be fatal, can happen even with blood sugar below 250 mg/dL, and has been reported in type 2 diabetes. It is checked for whatever the blood sugar, and Trijardy XR is stopped if it is suspected. It is not for type 1 diabetes.
Pancreatitis. Acute pancreatitis, including fatal cases, has been reported with linagliptin. In the CARMELINA trial it was 0.3% on linagliptin vs 0.1% on placebo. Trijardy XR is stopped promptly if it is suspected.
Volume depletion. Empagliflozin can cause fluid loss, low blood pressure and acute kidney injury, especially with kidney problems, in older people or with loop diuretics. Fluid status and kidney function are checked before starting.
Genitourinary infections, including Fournier's gangrene. Serious urinary infections, kidney infections, genital yeast infections and a rare, life-threatening 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 with insulin or a sulfonylurea. Low blood sugar risk rises with insulin or a medicine that makes the body release insulin, so a lower dose of those may be needed.
Lower limb amputation. An imbalance in lower limb amputations has been seen with SGLT2 inhibitors. People are watched for infections, new pain, sores or ulcers of the legs and feet.
Hypersensitivity reactions. Serious allergic reactions, including anaphylaxis, angioedema and skin peeling conditions, have been reported, mostly within the first 3 months. Trijardy XR 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.
Severe and disabling joint pain. Severe joint pain has been reported with linagliptin, starting from one day to years after starting, and easing after stopping.
Bullous pemphigoid. A blistering skin condition was reported in 0.2% on linagliptin vs none on placebo in CARMELINA. Trijardy XR is stopped if it is suspected.
Heart failure. Heart failure was linked to two other DPP-4 inhibitors. Risks and benefits are weighed in people at risk, and they are watched for symptoms.
From the Medication Guide that comes with Trijardy XR:
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.