Kombiglyze XR, illustration of tablet form (not a photo of the actual pack)

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Kombiglyze XR

Saxagliptin/Metformin

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FDA boxed warningLactic acidosis

Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure ), excessive alcohol intake, hepatic impairment, and mitochondrial diseases.

Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information.

If metformin-associated lactic acidosis is suspected, immediately discontinue saxagliptin and metformin hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL.

If lactic acidosis is suspected, discontinue saxagliptin and metformin hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Read this with the rest of the clinical information

About Kombiglyze XR

Overview

Kombiglyze XR is a prescription extended-release tablet containing saxagliptin and metformin hydrochloride. It is used alongside diet and exercise to improve blood sugar control in adults with type 2 diabetes. It combines two blood sugar-lowering medicines, with saxagliptin blocking an enzyme called DPP-4. It is not recommended for treating type 1 diabetes or diabetic ketoacidosis.

What it treats

Type 2 diabetes in adults, alongside diet and exercise, to improve blood sugar control.

Safety information

Side effects

Common side effects reported with saxagliptin and metformin include headache and inflammation of the nose and throat. Metformin extended-release can also cause diarrhea, nausea and vomiting. Saxagliptin can also cause upper respiratory tract infections and urinary tract infections. Serious side effects include lactic acidosis (a buildup of lactic acid in the blood), pancreatitis (inflammation of the pancreas), heart failure, low vitamin B12 levels, and low blood sugar when used with insulin or medicines that stimulate insulin release. Contact a doctor promptly if you suspect a serious side effect, develop severe or disabling joint pain, or notice skin blisters or erosions. Blistering may be a sign of bullous pemphigoid, which can require hospitalization. Serious allergic reactions, including anaphylaxis, swelling beneath the skin and peeling skin reactions, have also been reported and require immediate medical attention.

FDA boxed warning

Lactic acidosis

Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure ), excessive alcohol intake, hepatic impairment, and mitochondrial diseases.

Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information.

If metformin-associated lactic acidosis is suspected, immediately discontinue saxagliptin and metformin hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL.

If lactic acidosis is suspected, discontinue saxagliptin and metformin hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

A boxed warning is the strongest warning the US Food and Drug Administration requires on a medicine label. Text is taken from the official label, with internal section references removed.

When to call your doctor

- Seek medical attention immediately for trouble breathing, unusual sleepiness, muscle aches, stomach pain or feeling generally unwell. These can be signs of lactic acidosis, a potentially fatal reaction. - Contact your doctor immediately for severe or disabling joint pain. - Contact your doctor immediately if you develop skin blisters or open sores.

If symptoms are severe or getting worse quickly, seek emergency care rather than waiting.

Before taking this medicine

Do not take Kombiglyze XR if you have severe kidney impairment (eGFR below 30 mL/min/1.73 m²), acute or chronic metabolic acidosis, including diabetic ketoacidosis, or a history of a serious allergic reaction to saxagliptin, metformin or any tablet ingredient. Serious reactions include anaphylaxis, swelling beneath the skin (angioedema) and skin peeling. Use should be avoided in people with liver impairment. Extra caution and monitoring are needed if you have risk factors for heart failure. Older adults need more frequent kidney function checks. Metformin may lower vitamin B12 levels; blood counts should be checked annually. Taking this medicine with insulin or medicines that stimulate insulin release can increase the risk of low blood sugar, so your prescriber may need to adjust those medicines. Other serious concerns include inflammation of the pancreas (pancreatitis), severe joint pain and a blistering skin condition called bullous pemphigoid. Report new blisters or open sores to your prescriber. The medicine should be stopped promptly if pancreatitis or bullous pemphigoid is suspected, or if a serious allergic reaction occurs. Serious allergic reactions need prompt treatment. Severe joint pain may also require stopping treatment after medical assessment.

Interactions

Tell your doctor about other medicines you take. Important interactions include: • Strong CYP3A4/5 inhibitors, such as ketoconazole, can significantly increase saxagliptin levels. Your prescriber may need to adjust your prescription. • Carbonic anhydrase inhibitors may increase the risk of lactic acidosis, a build-up of lactic acid in the blood. • Medicines that reduce the body’s clearance of metformin may increase the risk of lactic acidosis. Medicines that affect kidney function, cause significant changes in blood flow or blood pressure, or disrupt the body’s acid–base balance may also increase this risk. Your doctor may need to monitor you more closely.

Using Kombiglyze XR

Dosing

Dosing is set by your prescriber. Each health care professional may prescribe medication differently according to a patient's medical history and condition, so follow the directions on your prescription label and speak to your doctor or pharmacist before changing anything.

Storage

Store below 25°C in a dry place, in the original pack, away from direct light and moisture. Do not keep it in a bathroom. Keep all medicines out of the sight and reach of children.

Clinical information on this page is summarised from the US FDA label SAXAGLIPTIN AND METFORMIN TABLET, FILM COATED, EXTENDED RELEASE [MYLAN PHARMACEUTICALS INC.] (DailyMed, retrieved 19 September 2026).

Patient information and references

Official and supporting information to read alongside advice from your prescriber or pharmacist.

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