Metformin/Sitagliptin

Metformin/Sitagliptin is a prescription medication used to treat Type 2 Diabetes Mellitus. 

• Metformin/Sitagliptin is available under the following different brand names: Janumet, Janumet XR.

Adult dosage

Tablet

• 500mg/50mg
• 1000mg/50mg

Tablet, extended-release

• 500mg/50mg
• 1000mg/50mg
• 1000mg/100mg

Type 2 Diabetes Mellitus 

Adult dosage

Not currently treated with metformin

• Immediate-release: 50 mg sitagliptin/500 mg metformin orally twice daily
• Extended-release: 100 mg sitagliptin/1000 mg metformin orally once daily
• Not to exceed a daily dose of 2000 mg of metformin or 100 mg of sitagliptin 

Currently treated with metformin

Immediate-release: 

• Sitagliptin 50 mg orally twice daily (100 mg/day) and a current daily dose of metformin
• For patients taking metformin HCL 850 mg twice daily, recommended starting dose is 50 mg sitagliptin/1000 mg metformin HCL orally twice daily

Extended-release

• Sitagliptin 100 mg and a current daily dose of metformin
• For patients taking metformin HCI immediate-release 850 mg or 1000 mg orally twice daily, recommended starting dose 100 mg sitagliptin/1000 mg metformin
• Not to exceed a daily dose of 2000 mg of metformin or 100 mg of sitagliptin

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Metformin/Sitagliptin include:

• low blood sugar, 
• upset stomach, 
• indigestion, 
• gas, 
• diarrhea, 
• nausea, 
• vomiting, 
• headache, 
• weakness, 
• runny or stuffy nose, 
• sneezing, and
• sore throat 

Serious side effects of Metformin/Sitagliptin include:

• hives, 
• difficult breathing, 
• swelling of the face, lips, tongue, or throat, 
• fever, 
• sore throat, 
• burning in the eyes, 
• skin pain, 
• red or purple skin rash that spreads and causes blistering and peeling, 
• severe pain in the stomach spreading to the back, 
• nausea, 
• vomiting, 
• loss of appetite, 
• fast heartbeats, 
• unusual muscle pain, 
• feeling cold, 
• dizziness, 
• lightheadedness, 
• tiredness, 
• weakness, 
• stomach pain, 
• irregular heart rate, 
• itching, 
• blisters, 
• breaking down of the outer layer of skin, 
• severe or ongoing pain in the joints, 
• little or no urination, 
• shortness of breath, 
• swelling in the legs or feet, and
• rapid weight gain

Rare side effects of Metformin/Sitagliptin include:

• none

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Metformin/Sitagliptin has severe interactions with no other drugs.
• Metformin/Sitagliptin has serious interactions with at least 15 other drugs.
• Metformin/Sitagliptin has moderate interactions with at least 226 other drugs.
• Metformin/Sitagliptin has minor interactions with at least 102 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• Serious hypersensitivity reaction (e.g., anaphylaxis, angioedema) to sitagliptin/metformin, sitagliptin, or metformin
• Severe renal impairment (eGFR less than 30 ml/min/1.73 m2)
• Acute/chronic metabolic acidosis, including diabetic ketoacidosis 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Metformin/Sitagliptin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Metformin/Sitagliptin?”

Cautions

• Metformin-associated lactic acidosis has been reported; cases primarily occurred in patients with significant renal impairment; assess renal function before initiating, at least annually during treatment, and more frequently in high-risk patients (eg, elderly)
• Acute pancreatitis was reported, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis; if pancreatitis is suspected, discontinue promptly
• Heart failure observed with other DPP-4 inhibitors; consider risks and benefits in patients with risk factors for heart failure; monitor for signs and symptoms; if heart failure develops, manage accordingly to the standard of care and consider interrupting treatment
• Acute renal failure reported, sometimes requiring dialysis; assess renal function before initiation and periodically thereafter
• Metformin may lower vitamin B12 levels; monitor hematologic parameters annually and Serious allergic and hypersensitivity reactions (eg, anaphylaxis, angioedema, exfoliative skin conditions including Stevens-Johnson syndrome) reported; promptly stop treatment and assess for other potential causes; appropriately monitor and treat
• Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
• Bullous pemphigoid reported with DPP-4 inhibitor use, which required hospitalization; in reported cases, patients recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP-4 inhibitor; advice to report any developing blisters/erosions; discontinue DPP-4 therapy and consult a dermatologist if bullous pemphigoid suspected

Drug interaction overview

• Sitagliptin is a P-gp and organic anion transporter-3 substrate; weak CYP3A4 and CYP2C8 substrates
• Insulin or insulin secretagogues
  • Increased risk of hypoglycemia when concomitantly used with insulin and/or an insulin secretagogue; consider lowering the dose of insulin or insulin secretagogue
• Carbonic anhydrase inhibitors
  • Consider more frequent monitoring
  • Coadministration of these drugs may increase the risk for lactic acidosis
• Drugs that reduce metformin clearance
  • Consider benefits and risks of coadministration
  • Drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis
• Alcohol
  • Warn against alcohol intake during treatment
  • Alcohol potentiates the effect of metformin on lactate metabolism
• Drugs affecting glycemic control
  • Closely monitor for loss of blood glucose control
  • When such drugs are discontinued, observe closely for hypoglycemia
  • Certain drugs (e.g., thiazides, corticosteroids) tend to produce hyperglycemia and may lead to loss of glycemic control

Pregnancy and Lactation

• Limited available data in pregnant females are not sufficient to inform a drug-associated risk for major birth defects and miscarriage

Metformin

• Published studies with use during pregnancy have not reported a clear association with drug and major birth defects or miscarriage risks

Pregnancy registry

• Monitors pregnancy outcomes in females exposed to drugs during pregnancy
• Encourage patients to report any prenatal exposure to drugs by calling 1-800-986-8999

Clinical considerations

• Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications
• Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity

Females and males of reproductive potential

• Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women
• There is no information regarding the presence of drugs in human milk, its effects on breastfed infants, or milk production

Sitagliptin

• Present in rat milk and therefore possibly present in human

Metformin

• Limited published studies report of drug presence in human milk
• No adverse effects were reported on breastfed infants exposed to metformin
• No information available on the effects of drugs on milk production