Metformin / Saxagliptin Side Effects

Medically reviewed by Drugs.com. Last updated on Oct 13, 2024.

Applies to metformin / saxagliptin: oral tablet extended release.

Precautions

Your doctor will want to 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.

Let your doctor or dentist know you are taking this medicine. Your doctor may advise you to temporarily Stop taking metformin / saxagliptin before you have major surgery or diagnostic tests, including procedures that use contrast dye.

Under certain conditions, too much metformin can cause a condition called lactic acidosis. The symptoms of lactic acidosis are severe, appear quickly, and usually occur when other health problems are present, such as a heart attack or kidney failure. Symptoms of lactic acidosis include abdominal or stomach discomfort, decreased appetite, diarrhea, fast or shallow breathing, a general feeling of discomfort, muscle pain or cramping, and unusual sleepiness, tiredness, or weakness. If symptoms of lactic acidosis occur, you should get immediate emergency medical help.

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

If you are rapidly gaining weight, having shortness of breath, chest pain, extreme tiredness or weakness, irregular breathing, irregular heartbeat, or excessive swelling of the hands, wrist, ankles, or feet, check with your doctor immediately. These may be symptoms of a heart problem.

This medicine may cause serious types of allergic reactions, including anaphylaxis and angioedema. These conditions may be life-threatening and require immediate medical attention. Check with your doctor right away if you have a rash, itching, a large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs, trouble breathing, or chest tightness.

This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with certain medicines. Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. 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 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 severe joint pain. Call your doctor right away if you have severe joint pain with this medicine.

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

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, metformin / saxagliptin 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 metformin / saxagliptin:

Other side effects

Some side effects of metformin / saxagliptin 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 metformin / saxagliptin: oral tablet extended release.

General adverse events

Among treatment naive patients' coadministered saxagliptin and metformin, the most commonly reported adverse events included headache and nasopharyngitis. Adverse reactions that are commonly reported with saxagliptin include respiratory tract infection, urinary tract infection, and headache; adverse reactions that are commonly reported with metformin include diarrhea and vomiting, especially on treatment initiation.^[Ref]

Metabolic

Saxagliptin-Metformin:

• Very common (10% or more): Hypoglycemia (in combination with insulin or sulfonylurea)
• Common (1% to 10%): Hypoglycemia
• Uncommon (0.1% to 1%): Blood creatinine phosphokinase increased

Metformin:

• Very rare: Lactic Acidosis^[Ref]

In metformin-treated patients, lactic acidosis has been reported in approximately 0.03 cases per 1000 patient-years with approximately half these cases resulting in fatalities. In more than 20,000 patient-years exposure in clinical trials, there were no cases of lactic acidosis. Reported cases have occurred primarily in patients with significant renal insufficiency, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications.

In saxagliptin monotherapy clinical trials, hypoglycemia was reported in 4%, 5.6%, and 4.1% of patients receiving saxagliptin 2.5 mg, 5 mg, and placebo, respectively. In add-on to metformin immediate-release, hypoglycemia was reported in 7.8%, 5.8%, and 5%, respectively.^[Ref]

Hypersensitivity

Saxagliptin:

• Common (1% to 10%): Hypersensitivity-related events such as urticaria and facial edema
• Postmarketing reports: Serious hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions^[Ref]

In a 5-study pooled analysis including patients receiving saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo, hypersensitivity-related events were reported in 1.5%, 1.5%, and 0.4%, respectively. None of the events required hospitalization or were reported as life-threatening. One saxagliptin-treated patient discontinued treatment due to generalized urticaria and facial edema. Postmarketing, there have been serious hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions reported.^[Ref]

Dermatologic

• Uncommon (0.1% to 1%): Rash
• Postmarketing reports: Angioedema, dermatitis, pruritus, rash, urticaria^[Ref]

Gastrointestinal

• Common (1% to 10%): Dyspepsia, gastritis, flatulence

Saxagliptin:

• Common (1% to 10%): Abdominal pain, gastroenteritis, vomiting
• Postmarketing reports: Acute pancreatitis

Metformin:

• Common (1% to 10%): Diarrhea, nausea, vomiting, abdominal pain,^[Ref]

Frequently during treatment initiation of metformin gastrointestinal effects have occurred and these appear to resolve spontaneously in most cases. A slow increase in dose and dividing doses and taking during or after meals may improve gastrointestinal tolerability. In metformin extended-release monotherapy trials, diarrhea and nausea/vomiting were reported in 9.6% and 6.5% of patients compared with 2.6% and 1.5% of placebo patients, respectively.

Acute pancreatitis has been reported during postmarketing use of saxagliptin. In the SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial infarction) Trial, the incidence of adjudicated pancreatitis events in the intention to treat population was 0.3% in both the saxagliptin treated patients as well as those receiving placebo.^[Ref]

Saxagliptin-Metformin

Hematologic

Saxagliptin:

• Uncommon (0.1% to 1%): Lymphopenia
• Frequency not reported: Thrombocytopenia

Metformin:

• Rare (less than 0.1%): Megaloblastic anemia due to reduced vitamin B12 absorption^[Ref]

A dose-related mean decrease in absolute lymphocyte count was observed during clinical trials. The proportion of patients with lymphocyte counts of 750 cells/microL or less was 0.5%, 1.5%, 1.4%, and 0.4% in patients receiving saxagliptin 2.5 mg, 5 mg, 10 mg (not an approved dosage), and placebo, respectively. In most patients, recurrence was not observed with repeated exposure, although some discontinuations were associated with recurrent decrease upon rechallenge. During clinical trials, these decreases in lymphocyte count were not associated with clinically relevant adverse reactions, but whether these decreases may become a concern is unknown. When clinically indicated, such as in settings of unusual or prolonged infection, lymphocyte count should be measured. The effect of saxagliptin on lymphocyte counts in patients with lymphocyte abnormalities (e.g., HIV) is unknown.^[Ref]

Hepatic

Metformin:

• Very rare (less than 0.01%): Liver function disorders, hepatitis^[Ref]

Cardiovascular

• Common (1% to 10%): Hospitalization for heart failure, hypertension, peripheral edema (in combination with a thiazolidinedione)^[Ref]

In the SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial infarction) Trial, hospitalization for heart failure (secondary composite endpoint) occurred at a greater rate in the saxagliptin group (3.5%) compared with the placebo group (2.8%), however clinically relevant factors predictive of increased relative risk with saxagliptin could not be definitively identified. Known risk factors for heart failure such as baseline history of heart failure or impaired renal function did confer increased risk, irrespective of treatment assignment. The primary composite endpoints for all-cause mortality showed saxagliptin did not increase the cardiovascular (CV) risk(CV death, nonfatal myocardial infarction, or nonfatal ischemic stroke) in patients with type 2 diabetes mellitus compared to placebo when added to current background therapy.^[Ref]

Genitourinary

• Common (1% to 10%): Urinary tract infection
• Uncommon (0.1% to 1%): Erectile dysfunction^[Ref]

Immunologic

Saxagliptin:

• Uncommon (0.1% to 1%): Tuberculosis
• Very rare (less than 0.01%): Potential opportunistic infection (salmonella)^[Ref]

Among 4959 saxagliptin-treated patients in clinical trials, 6 cases of tuberculosis have been received; no reports of tuberculosis have been received among the 2868 comparator-treated patients. Causality has not been established and there are too few cases to date to determine any relation to saxagliptin use. None of the cases occurred in the U.S. or in Western Europe; 1 case occurred in Canada in a patient originally from Indonesia who had recently visited Indonesia.

One case of a potential opportunistic infection occurred in a saxagliptin-treated patient. Approximately 600 days after starting saxagliptin, this patient developed fatal salmonella sepsis.^[Ref]

Musculoskeletal

• Common (1% to 10%): Myalgia
• Uncommon (0.1% to 1%): 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]

Nervous system

Saxagliptin-Metformin:

• Common (1% to 10%): Headache

Saxagliptin:

• Common (1% to 10%): Dizziness

Metformin:

• Common (1% to 10%): Metallic taste^[Ref]

Respiratory

• Common (1% to 10%): Upper respiratory tract infection, sinusitis, nasopharyngitis^[Ref]

Renal

• Uncommon (0.1% to 1%): Blood creatinine increased^[Ref]

Other

Saxagliptin:

• Common (1% to 10%): Fatigue^[Ref]

See also:

Frequently asked questions

• What are the ingredient drugs contained in Qternmet XR?

Further information

Metformin/saxagliptin 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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