Ertugliflozin / Metformin Side Effects

Medically reviewed by Drugs.com. Last updated on Jan 10, 2025.

Applies to ertugliflozin / metformin: oral tablet.

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.

Using this medicine during the second and later part of a pregnancy can harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor right away.

Under certain conditions, too much metformin can cause a serious condition called lactic acidosis. It usually occurs when other serious health problems are present, including heart attack or kidney failure. Check with your doctor right away if you have decreased appetite, diarrhea, fast or shallow breathing, a general feeling of discomfort, muscle pain or cramping, stomach discomfort, and unusual sleepiness, tiredness, or weakness. If you have more than one of these symptoms together, you should get immediate emergency medical help.

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). Drinking 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.

Diabetic 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, or increased thirst or urination.

Tell your doctor if you have bloody urine, decrease in how much or how often you urinate, painful or difficult urination, lower back or side pain, fever, chills, or swelling of the face, finger, or lower legs. These may be symptoms of a serious kidney problem.

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

This medicine can cause hypoglycemia (low blood sugar). However, low blood sugar can occur if you delay or miss a meal or snack, exercise more than usual, drink alcohol, cannot eat because of nausea or vomiting, or take certain medicines. Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. 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 the best way to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your diabetes medicine, overeat or do not follow your diet 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.Some symptoms of high blood sugar include blurred vision, drowsiness, dry mouth, flushed and dry skin, a fruit-like breath odor, increased frequency and amount of urination, ketones in the urine, loss of appetite, nausea or vomiting, rapid and deep breathing, tiredness, or unusual thirst. 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 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 cause some women who do not have regular monthly periods to ovulate. This can increase the chance of pregnancy. If you are a woman of childbearing potential, you should discuss birth control options with your doctor.

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 4 days before you have major surgery, diagnostic tests (especially tests that use a contrast dye), 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 drink a lot of alcohol while you are using this medicine. Heavy alcohol use can increase your risk for lactic acidosis.

There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says you have diabetes with a list of all your medicines.

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

Along with its needed effects, ertugliflozin / metformin 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 ertugliflozin / metformin:

Other side effects

Some side effects of ertugliflozin / metformin 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 ertugliflozin / metformin: oral tablet.

General adverse events

The most commonly reported adverse events with ertugliflozin have included genital mycotic infections, more common in females, but also occurring in males; the most commonly reported adverse events with metformin have included diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.^[Ref]

Metabolic

Ertugliflozin:

• Very common (10% or more): Hypoglycemia (in combination with insulin and/or insulin secretagogue in patients with moderate renal impairment; up to 27%)
• Common (1% to 10%): Decreased weight, hypoglycemia
• Rare (0.01% to 0.1%): Ketoacidosis
• Frequency not reported: Increases in low-density lipoprotein cholesterol (LDL-C), increased serum phosphate

Metformin:

• Common (1% to 10%): Hypoglycemia
• Very rare (less than 0.01%): Lactic acidosis

Ketoacidosis was reported in 3 of 3409 (0.1%) patients treated with this drug during clinical trials; no cases were identified in comparator-treated patients. Mean increases in low-density lipoprotein cholesterol (LDL-C) relative to placebo were 2.6% and 5.4%, in the 5 mg and 15 mg groups, respectively

Genitourinary

Ertugliflozin:

• Very common (10% or more): Female genital mycotic infections (up to 12.2%)
• Common (1% to 10%): Male genital mycotic infections, urinary tract infections, vaginal pruritus, increased urination
• Frequency not reported: Pyelonephritis

SGLT2 Inhibitors:

• Postmarketing reports: Serious urinary tract infections including urosepsis and pyelonephritis, Fournier's gangrene^[Ref]

Female genital mycotic infections include genital candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis. Male genital mycotic infections balanitis candida, balanoposthitis, genital infection, and genital infection fungal. Urinary tract infections include cystitis, dysuria, streptococcal urinary tract infection, urethritis, urinary tract infection. Vaginal pruritus includes vulvovaginal pruritus and pruritus genital. Increased urination includes pollakiuria, micturition urgency, polyuria, urine output increased, and nocturia.

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]

Renal

Ertugliflozin:

• Common (1% to 10%): Renal related adverse reactions
• Frequency not reported: Increased serum creatinine, decreased eGFR

SGLT2 Inhibitors:

• Postmarketing reports: Acute Kidney Injury

Renal related adverse reactions included acute kidney injury, renal impairment, acute prerenal failure. The incidence of renal related adverse reactions was 0.6%, 2.5%, and 1.3% in patients receiving placebo, 5 mg, and 15 mg, respectively.

Gastrointestinal

Ertugliflozin:

• Common (1% to 10%): Thirst

Metformin:

• Common (1% to 10%): Diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion

Thirst includes thirst, dry mouth, polydipsia, and dry throat.

Hepatic

Ertugliflozin:

• Frequency not reported: Increased serum phosphate

Cardiovascular

Ertugliflozin:

• Common (1% to 10%): Adverse reactions related to volume depletion

Adverse reactions related to volume depletion include dehydration, dizziness, postural, presyncope, syncope, hypotension, and orthostatic hypotension.

Musculoskeletal

Ertugliflozin:

• Common (1% to 10%): Back pain
• Uncommon (0.1% to 1%): Nontraumatic lower limb amputation

Nontraumatic lower limb amputation was reported in 3 (0.2%) patients receiving 5 mg and 8 patients (0.5%) receiving 15 mg; there was 1 report (0.1%) in the comparator group. A causal association between this drug and lower limb amputation has not been definitively established.

Hematologic

Ertugliflozin:

• Rare (0.01% to 0.1%): Hemoglobin increased greater than 2 g/dL and above the upper limit of normal

Metformin:

• Frequency not reported: Vitamin B12 deficiency

Respiratory

Ertugliflozin:

• Common (1% to 10%): Nasopharyngitis

Other

Metformin:

• Common (1% to 10%): Asthenia

Nervous system

Ertugliflozin:

• Common (1% to 10%): Headache

Metformin:

• Common (1% to 10%): Headache

See also:

Further information

Ertugliflozin/metformin 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.

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