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Metformin / sitagliptin Side Effects

In Summary

Commonly reported side effects of metformin/sitagliptin include: lactic acidosis. Other side effects include: nausea. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to metformin / sitagliptin: oral tablet, oral tablet extended release

Along with its needed effects, metformin/sitagliptin 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 / sitagliptin:

Less Common

Rare

  • Decreased appetite
  • diarrhea
  • fast, shallow breathing
  • general feeling of discomfort
  • muscle pain or cramping
  • sleepiness
  • stomach discomfort

Incidence Not Known

  • Blistering, peeling, or loosening of the skin
  • darkened urine
  • hives or welts, itching, or skin rash
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • red skin lesions, often with a purple center
  • severe joint pain
  • sores, ulcers, or white spots in the mouth or on the lips
  • vomiting
  • yellow eyes or skin

Some side effects of metformin / sitagliptin 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

  • Bloated or feeling of fullness
  • excess air or gas in the stomach or intestines
  • indigestion
  • lack or loss of strength
  • muscle aches
  • passing gas
  • sore throat
  • stuffy or runny nose
  • vomiting

For Healthcare Professionals

Applies to metformin / sitagliptin: oral tablet, oral tablet extended release

Metabolic

Metformin-sitagliptin:

Very common (10% or more): Hypoglycemia (13.8% when combined with sulfonylurea; 10.9% when combined with insulin)

Common (1% to 10%): Hypoglycemia, decrease levels of vitamin B12 without clinical manifestations and rarely associated with anemia

Rare (less than 0.1%): Lactic acidosis due to metformin

Sitagliptin:

Uncommon (0.1% to 1%): Hypoglycemia

Metformin:

Common (1% to 10%): Hypoglycemia (5% or more when combined with glyburide)

Uncommon (0.1% to 1%): Hypoglycemia

Very rare (less than 0.01%): Lactic acidosis, vitamin B12 deficiency[Ref]

In metformin-treated patients, the incidence of lactic acidosis has been about 1.5 cases per 10,000 patient years. The risk of lactic acidosis has been particularly high in patients with underlying renal insufficiency and rarely in patients with normal renal function. Concomitant cardiovascular or liver disease, sepsis, and hypoxia have also increased the risk of lactic acidosis.

Signs and symptoms of severe acidosis may include vomiting, abdominal pain, nausea, dyspnea, hypothermia, hypotension, and bradycardia.

Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption. Malabsorption of vitamin B12, due to intrinsic factor deficiency and possibly other mechanisms, in as many as 30% of treated patients, were reported. Megaloblastic anemia has occurred. Decreased levels of vitamin B12 appear to be reversible with discontinuation of metformin or vitamin B12 supplementation.[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, nausea, flatulence, vomiting

Uncommon (0.1% to 1%): Constipation, upper abdominal pain, dry mouth

Postmarketing reports: Indigestion, abdominal discomfort, dyspepsia, abdominal pain, acute pancreatitis (including fatal and non-fatal hemorrhagic and necrotizing pancreatitis), mouth ulceration, stomatitis

Metformin:

Very common (10% or more): Nausea, vomiting, diarrhea, abdominal pain, loss of appetite

Sitagliptin:

Rare (less than 0.1%): Pancreatitis[Ref]

Nervous system

Metformin-sitagliptin:

Common (1% to 10%): Headache

Uncommon (0.1% to 1%): Somnolence

Frequency not reported: Asthenia

Metformin:

Common (1% to 10%): metallic taste[Ref]

Respiratory

Common (1% to 10%): Upper respiratory tract infections, nasopharyngitis, pharyngolaryngeal pain, bronchitis, sinusitis, influenza

Postmarketing reports: Interstitial lung disease[Ref]

Hypersensitivity

Frequency not reported: Hypersensitivity reactions including anaphylaxis[Ref]

Hepatic

Metformin-sitagliptin:

Postmarketing reports: Hepatic enzyme elevation

Metformin:

Very rare (less than 0.01%): Liver function disorders, hepatitis

Renal

Frequency not reported: Impaired renal function, acute renal failure (sometimes requiring dialysis)

Musculoskeletal

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]

Common (1% to 10%): Arthralgia

Postmarketing reports: Myalgia, pain in extremities, back pain[Ref]

General

Common (1% to 10%): Peripheral edema

Dermatologic

Postmarketing reports: Angioedema, rash, urticaria, pruritus, cutaneous vasculitis, exfoliative skin conditions including Steven-Johnson syndrome

Metformin:

Very rare (less than 0.01%): Urticaria, erythema, pruritus

Hematologic

Rare (less than 0.1%): Megaloblastic anemia[Ref]

Decreased serum vitamin B12 levels, without clinical manifestations (rarely megaloblastic anemia), has been reported in approximately 7% of patients. The reduction in vitamin B12 levels may be due to interference with B12 absorption from the B12-intrinsic factor complex and appears to be rapidly reversible with discontinuation of metformin or vitamin B12 supplementation.[Ref]

References

1. "Product Information. Janumet (metformin-sitagliptin)." Merck & Company Inc, West Point, PA.

2. US Food and Drug Administration "FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. Available from: URL: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM460038.pdf." ([2015, Aug 28]):

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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