Glyxambi Side Effects

Generic name: empagliflozin / linagliptin

Medically reviewed by Drugs.com. Last updated on Jul 25, 2024.

Note: This document provides detailed information about Glyxambi.

Applies to empagliflozin / linagliptin: oral tablet, tablet oral Side Effects associated with empagliflozin / linagliptin. Some dosage forms listed on this page may not apply specifically to the brand name Glyxambi.

Applies to empagliflozin / linagliptin: oral tablet, tablet oral.

Precautions

It is very important that your doctor check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects.

Tell your doctor if you are pregnant or planning to become pregnant. It is not safe to take this medicine during the second and third trimester of pregnancy. It could harm an unborn baby.

Pancreatitis (swelling of the pancreas) may occur while you are using this medicine. Check with your doctor right away if you have a sudden and severe stomach pain, chills, constipation, nausea, vomiting, loss of appetite, fever, or lightheadedness.

Check with your doctor right away if you have chest pain or tightness, decreased urine output, dilated neck veins, extreme fatigue, irregular breathing, irregular heartbeat, swelling of the face, fingers, feet, or lower legs, trouble breathing, or weight gain. These may be signs of heart failure.

Dizziness, lightheadedness, or fainting may occur with this medicine. This is more common if you have kidney disease, low blood pressure, or if you are taking a diuretic (water pill). Taking plenty of fluids each day may help. Drink plenty of water during exercise or in hot weather. Check with your doctor if you have severe nausea, vomiting, or diarrhea that does not stop. This may cause you to lose too much water.

Ketoacidosis (high ketones and acid in the blood) may occur while you are using this medicine. This can be life-threatening and requires immediate medical attention. Your doctor may give you insulin, fluid, and carbohydrate replacement to treat this condition. Tell your doctor right away if you have nausea, vomiting, trouble breathing, increased thirst or urination.

This medicine may increase your risk of having kidney problems, including acute kidney injury or damaged kidney function. Check with your doctor right away if you have blood in the urine, decreased urine output, muscle twitching, nausea, rapid weight gain, seizures, stupor, swelling of the face, ankles, or hands, or unusual tiredness or weakness.

This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with other diabetes medicines (eg, insulin, glipizide, or glyburide). The symptoms of low blood sugar must be treated before they cause you to pass out. People feel different symptoms with low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Some symptoms of low blood sugar include: behavior changes that are similar to being drunk, blurred vision, cold sweats, confusion, cool, pale skin, difficulty with thinking, drowsiness, excessive hunger, a fast heartbeat, headaches that continue, nausea, shakiness, slurred speech, or unusual tiredness or weakness. Talk to your doctor about how to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your medicine, overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual. High blood sugar can be very serious and must be treated right away. It is important that you learn which symptoms you have in order to treat it quickly. Talk to your doctor about the best way to treat high blood sugar.

This medicine may cause vaginal yeast infections in women and yeast infections of the penis in men. This is more common in patients who have a history of genital yeast infections or in men who are not circumcised. Women may have a vaginal discharge, itching, or odor. Men may have redness, itching, swelling, or pain around the penis, or a discharge with a strong odor from the penis. Check with your doctor right away if you have any of these symptoms.

This medicine may increase risk of having urinary tract infections, including pyelonephritis or urosepsis. Check with your doctor right away if you have bladder pain, bloody or cloudy urine, difficult, burning, or painful urination, or lower back or side pain.

This medicine may cause a rare but serious bacterial infection, called necrotizing fasciitis of the perineum or Fournier's gangrene, which can cause damage to the tissue under the skin in the area between and around the anus and genitals (perineum). Fournier's gangrene may lead to hospitalization, multiple surgeries, or death. Check with your doctor right away if you have fever, unusual tiredness or weakness, or pain, tenderness, redness, or swelling of the area between and around your anus and genitals.

This medicine may increase your risk of having lower leg, foot, or toe amputation. Check with your doctor right away if you have pain, tenderness, sores or ulcers, or infections in your leg or foot.

This medicine may cause serious allergic reactions, including anaphylaxis, angioedema, and other skin conditions, which can be life-threatening and require immediate medical attention. Call your doctor right away if you have a chest tightness, cough, difficulty swallowing, dizziness, rash, itching, trouble breathing, trouble swallowing, or puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue while you are using this medicine.

This medicine may cause severe and disabling joint pain. Call your doctor right away if you have severe joint pain while using this medicine.

This medicine may cause bullous pemphigoid. Tell your doctor if you have large, hard skin blisters while using this medicine.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine at least 3 days before having major surgery or other procedures that require fasting. This medicine may also affect the results of certain medical tests (eg, urine glucose tests may not be accurate).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Serious side effects of Glyxambi

Along with its needed effects, empagliflozin/linagliptin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking empagliflozin / linagliptin:

Other side effects of Glyxambi

Some side effects of empagliflozin / linagliptin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

For healthcare professionals

Applies to empagliflozin / linagliptin: oral tablet.

General adverse events

The most commonly occurring adverse events have included urinary tract infections, nasopharyngitis, and upper respiratory tract infections.^[Ref]

Gastrointestinal

• Postmarketing reports: Acute Pancreatitis, mouth ulcerations, stomatitis

Empagliflozin:

• Common (1% to 10%): Nausea

Linagliptin:

• Common (1% to 10%): Diarrhea
• Frequency not reported: Pancreatitis
• Postmarketing reports: Acute pancreatitis, mouth ulceration^[Ref]

During clinical trials, pancreatitis was reported in 15.2 cases per 10,000 patient year exposure in linagliptin-treated patients compared to 3.7 cases per 10,000 in those receiving active comparator (placebo or sulfonylurea). Following completion of clinical trials, 3 additional cases of pancreatitis were reported. Postmarketing reports of acute pancreatitis, including fatalities, have been reported.^[Ref]

Empagliflozin-linagliptin

Dermatologic

• Postmarketing reports: Bullous pemphigoid, skin reactions (e.g., rash, urticaria)

Empagliflozin:

• Common (1% to 10%): Pruritus
• Postmarketing reports: Rash

Linagliptin:

• Postmarketing reports: Rash, bullous pemphigoid^[Ref]

Postmarketing reports of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitors. Discontinuation of therapy and treatment with topical or systemic immunosuppressive agents led to resolution in reported cases.^[Ref]

Empagliflozin-linagliptin

Metabolic

Empagliflozin-linagliptin:

• Common (1% to 10%): Hypoglycemia, increased cholesterol, thirst
• Postmarketing reports: Ketoacidosis

Empagliflozin:

• Common (1% to 10%): Increased low-density lipoprotein cholesterol, dyslipidemia
• Rare (Less than 0.1%): Ketoacidosis
• Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis

Linagliptin:

• Common (1% to 10%): Increased uric acid^[Ref]

When this combination product was added to metformin therapy, the overall incidence of hypoglycemia was 2.2% and 3.6% in patients receiving empagliflozin 10 mg-linagliptin 5 mg and empagliflozin 25 mg-linagliptin 5 mg, respectively. There were no reports of serious hypoglycemia.

Twenty reports of acidosis have been identified in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database during the period March 2013 through 06 June 2014. All patients required emergency room treatment or hospitalization. These cases were not typical of ketoacidosis or diabetic ketoacidosis (DKA) in that they occurred in patients with type 2 diabetes and their blood sugar levels were only slightly increased. Some factors identified as potentially triggering the acidosis included major illness, reduced food and fluid intake, and reduced insulin dose.^[Ref]

Genitourinary

Empagliflozin-linagliptin:

• Very common (10% or more): Urinary tract infection (up to 12.5%)
• Postmarketing reports: Urosepsis, pyelonephritis, Fournier's gangrene

Empagliflozin:

• Common (1% to 10%): Urinary tract infection, female genital mycotic infections, vaginal moniliasis, vulvovaginitis, balanitis, increased urination, male genital mycotic infections
• Uncommon (0.1% to 1%): Dysuria
• Postmarketing reports: Fournier's gangrene^[Ref]

In the 5 years (2013 to 2018) since SGLT2 inhibitor approval, 12 cases of Fournier's gangrene have been reported. Reports were almost equal in men and women (men=7; women=5), ages ranged from 38 to 78 years, and the average time to onset after starting an SGLT2 inhibitor was 9.2 months (range 7 days to 25 months). All SGLT2 inhibitor drugs except ertugliflozin were included in the reports. Ertugliflozin being the most recently approved agent, is expected to have the same risk, but insufficient patient use to assess risk. All patients were hospitalized, all required surgery, all required surgical debridement, 5 required more than 1 surgery and 1 required skin grafting. Four cases were complicated by diabetic ketoacidosis, acute kidney injury, and septic shock, leading to prolonged hospitalization, and death in 1 case. In the general population, Fournier's gangrene occurs in about 1.6 out of 100,000 males annually, with the highest incidence in men 50 to 79 years. Since diabetes is a risk factor for Fournier's gangrene, a review of the FAERS database for the last 34 years was done and only 6 cases (all males, median age 57 years) were found with several other classes of antidiabetic drugs. Findings with SGLT2 inhibitors appear to show an association over a shorter time frame and involve both males and females.^[Ref]

Hypersensitivity

Empagliflozin-linagliptin:

• Uncommon (0.1% to 1%): Hypersensitivity
• Postmarketing reports: Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions

Linagliptin:

• Frequency not reported: Hypersensitivity reactions including urticaria, angioedema, localized skin exfoliation, or bronchial hyper-reactivity
• Postmarketing reports: Serious hypersensitivity reactions including anaphylaxis, angioedema^[Ref]

Postmarketing, serious hypersensitivity reactions including angioedema, anaphylaxis, and exfoliative skin conditions have been reported in patients treated with linagliptin. These reactions have occurred within the first 3 months and some have occurred after the first dose.^[Ref]

Renal

• Postmarketing reports: Acute kidney injury

Empagliflozin:

• Frequency not reported: Increased serum creatinine, decreased eGFR
• Postmarketing reports: Acute kidney injury (AKI)^[Ref]

Postmarketing reports of AKI, some requiring hospitalization and dialysis, have been received for patients treated with SGLT2 inhibitors including empagliflozin. Some reports involved patients younger than 65 years old.^[Ref]

Empagliflozin-linagliptin

Respiratory

Empagliflozin-Linagliptin:

• Common (1% to 10%): Nasopharyngitis, upper respiratory infection

Empagliflozin:

• Common (1% to 10%): Upper respiratory infection

Linagliptin:

• Common (1% to 10%): Nasopharyngitis, cough^[Ref]

Musculoskeletal

• Postmarketing reports: Severe and disabling arthralgia, rhabdomyolysis

Dipeptidyl peptidase-4 (DPP-4) inhibitors:

• Common (1% to 10%): Arthralgia

Postmarketing cases: Severe and disabling arthralgia^[Ref]

Between October 2006 and December 2013, thirty-three cases of severe arthralgia have been reported to the FDA Adverse Event Reporting System Database. Each case involved the use of 1 or more dipeptidyl peptidase-4 (DPP-4) inhibitor. In all cases, substantial reduction in prior activity level was reported, 10 patients were hospitalized due to disabling joint pain. In 22 cases, symptoms appeared within 1 month of starting therapy, in 23 cases symptoms resolved less than 1 month after discontinuation. A positive rechallenge was reported in 8 cases, with 6 cases involving use of a different DPP-4 inhibitor. Sitagliptin had the greatest number of cases reported (n=28) followed by saxagliptin (n=5), linagliptin (n=2), alogliptin (n=1), and vildagliptin (n=2).^[Ref]

Empagliflozin-linagliptin

Cardiovascular

Empagliflozin:

• Uncommon (0.1% to 1%): Volume depletion

Hematologic

Empagliflozin-Linagliptin:

• Frequency not reported: Increased hematocrit

Empagliflozin:

• Common (1% to 10%): Increased hematocrit^[Ref]

See also:

Further information

Glyxambi side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer