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Ertugliflozin / metformin Side Effects

Medically reviewed by Drugs.com. Last updated on Aug 23, 2023.

Applies to ertugliflozin / metformin: oral tablet.

Warning

Oral route (Tablet)

Death, hypothermia, hypotension, and resistant bradyarrhythmias have been reported due to metformin-associated lactic acidosis. Onset may be subtle and include nonspecific symptoms such as malaise, myalgia, respiratory distress, somnolence, and abdominal distress; laboratory abnormalities include low pH, increased anion gap and elevated blood lactate. The risk of lactic acidosis increases with renal or hepatic impairment, aged 65 years or older, having a radiological study with contrast, surgery, or other procedures, hypoxic states, and excessive alcohol intake. If lactic acidosis is suspected, ertugliflozin and metformin hydrochloride should be discontinued, supportive measures started in a hospital setting. Prompt hemodialysis is recommended.

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:

More common

Less common

Rare

Incidence not known

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:

More common

Less common

For Healthcare Professionals

Applies to ertugliflozin / metformin: oral tablet.

General

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

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

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

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

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.

Ertugliflozin:

Common (1% to 10%): Renal related adverse reactions

Frequency not reported: Increased serum creatinine, decreased eGFR

SGLT2 Inhibitors:

Postmarketing reports: Acute Kidney Injury

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

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

Ertugliflozin:

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

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

References

1. Product Information. Segluromet (ertugliflozin-metformin). Merck & Co., Inc. 2017.

2. FDA. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM618466.pdf 2018.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

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