Metformin / Sitagliptin Dosage

Medically reviewed by Drugs.com. Last updated on Feb 26, 2024.

Usual Adult Dose for Diabetes Type 2

Dose should be individualized based on patient's current regimen, effectiveness, and tolerability.

IMMEDIATE-RELEASE:

• Initial dose for patients not receiving metformin: sitagliptin 50 mg/metformin 500 mg orally twice a day
• Initial dose for patients receiving metformin: sitagliptin 50 mg in combination with half the daily dose of metformin orally twice a day (i.e, equal to same total daily dose of metformin currently being administered)

EXTENDED-RELEASE:

• Initial dose for patients not receiving metformin: sitagliptin 100 mg/metformin 1000 mg orally once a day
• Initial dose for patients receiving metformin: sitagliptin 100 mg in combination with current daily metformin dose orally once a day

TITRATE metformin dose slowly to reduce gastrointestinal side effects; titrate combination dose to achieve optimal glycemic control
MAXIMUM: Sitagliptin 100 mg/day; Metformin 2000 mg/day

Comments:

• The same daily dose of metformin and sitagliptin should be maintained if need to change between immediate-release and extended-release products.
• When initiating therapy, a dose adjustment of insulin secretagogue (e.g., sulfonylurea) or insulin may be necessary to reduce the risk of hypoglycemia.

Use: As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

Renal Dose Adjustments

Mild renal impairment (eGFR greater than 45 mL/min/1.73 m2): No dose adjustments recommended
Moderate renal impairment (eGFR 30 to 45 mL/min/1.73 m2): Initiating therapy is not recommended
Severe renal impairment (eGFR less than 30 mL/min/1.73 m2): Use is contraindicated

If eGFR falls below 30 mL/min/1.73 m2 during therapy: Discontinue therapy
If eGFR falls below 45 mL/min/1.73 m2 during therapy: Assess risks versus benefit of continued therapy AND limit the sitagliptin component to 50 mg/day

IODINATED CONTRAST PROCEDURE:

• For patients with eGFR between 30 and 60 mL/min/1.73 m2: Stop therapy at time of, or before imaging procedure; re-evaluate eGFR 48 hours after procedure; restart therapy only if renal function is stable
• For patients receiving intra-arterial iodinated contrast: Stop therapy at time of, or before imaging procedure; re-evaluate eGFR 48 hours after procedure; restart therapy only if renal function is stable

Liver Dose Adjustments

Hepatic impairment: Use not recommended

IODINATED CONTRAST PROCEDURE:

• For patients with a history of hepatic impairment: Stop therapy at time of, or before imaging procedure; re-evaluate eGFR 48 hours after procedure; restart therapy only if renal function is stable
• For patients receiving intra-arterial iodinated contrast: Stop therapy at time of, or before imaging procedure; re-evaluate eGFR 48 hours after procedure; restart therapy only if renal function is stable

Dose Adjustments

Elderly: Dose selection should be cautious usually starting at the low end of the dosing range; assess renal function frequently

Radiological Studies with Contrast:

• Stop this drug at time of, or prior to an iodinated contrast imaging procedure using intra-arterial iodinated contrast
• Stop this drug at time of, or prior to an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2, in patients with a history of hepatic impairment, alcoholism, or heart failure
• Re-evaluate eGFR 48 hours after procedure and restart only if renal function is stable

Heart Failure:

• If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of this drug

Precautions

US BOXED WARNINGS: LACTIC ACIDOSIS

• Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Onset is often subtle, accompanied by only nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally greater than 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, and hepatic impairment.
• Steps to reduce the risk of and manage metformin-associated lactic acidosis in high risk groups are provided in the full prescribing information.
• If metformin-associated lactic acidosis is suspected, immediately discontinue therapy and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

CONTRAINDICATIONS:

• Severe renal impairment (eGFR below 30 mL/min/1.73 m2)
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis
• History of a serious hypersensitivity reaction to the active substances such as anaphylaxis or angioedema

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Contraindicated in patients with moderate to severe renal dysfunction
Hemodialysis:

• Metformin is dialyzable with a clearance of up to 170 mL/min
• Sitagliptin is modestly dialyzable

Peritoneal dialysis: Data not available

Other Comments

Administration advice:

• Immediate-release: Take orally twice a day with meals; swallow whole, do not split or divide
• Extended-release: Take orally once a day with the evening meal; swallow whole, do not crush, cut, or chew
• If a dose is missed, take with food as soon as remembered, but if it is time for the next dose, skip the missed dose; do not take 2 doses as the same time.

General:

• In clinical trials, sitagliptin has not been shown to improve glycemic control in pediatric patients 10 to 17 years old with type 2 diabetes; this drug is not approved for use in pediatric patients.
• Occasionally, a mass resembling the extended-release tablet (XR) may be eliminated in the feces. It is not known whether this mass contains active drug, but if a patient repeatedly sees tablets in their feces, glycemic control should be assessed.
• This drug may need to be stopped at the time or prior to radiologic studies utilizing iodinated contrast materials; if hold is needed, hold for 48 hours after procedure and resume only after adequate renal function is confirmed.
• This drug should be held for surgical procedures, or anytime restricted food or fluid intake is expected; may resume once adequate renal function is confirmed.
• This drug should not be used in patients with type 1 diabetes mellitus.
• This drug has not been studied in patients with a history of pancreatitis; it is unknown whether patients with a history of pancreatitis are at increased risk for the developing pancreatitis.

Monitoring:

• Monitor glycemic control
• Renal: Assess renal function at baseline and at least annually, more frequent (e.g. every 3 to 6 months) monitoring is recommended when serum creatinine levels are at the upper limit of normal, for elderly patients, and for patients at risk for developing renal impairment
• Hematologic: Measure hematologic parameters annually
• Monitor for signs and symptoms of pancreatitis
• Monitor for skin disorders such as blistering or ulceration

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Medication Guide).
• Instruct patient to report signs and symptoms of pancreatitis; if persistent, severe abdominal pain occurs, seek medical advice promptly.
• Inform patients about the risk of lactic acidosis, conditions that might predispose them to its occurrence, and symptoms to watch for and report.
• Advise patient that this drug may need to be temporarily stopped if undergoing radiologic studies with intravascular iodinated contrast materials or surgical procedures that will limit food or fluid intake.
• Patients should be instructed to reports symptoms of heart failure, severe and persistent joint pain, or skin blistering or ulceration.
• Patients should understand the importance of adhering to dietary instructions and regular physical activity; during periods of stress such as fever, trauma, infection, or surgery, management of diabetes may change and patients should be advised to seek medical advice.
• Patients should understand the risk of hypoglycemia is increased when this drug is added an an insulin secretagogue or insulin therapy; patients should understand what action they need to take if they experience increased or decreased blood sugars.
• Advise patients on the risks of excessive alcohol intake.

Further information

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

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