What are the common side effects of Janumet (sitagliptin and metformin)?

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Last updated: June 30, 2025View editorial policy

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From the Guidelines

Janumet, a combination medication containing sitagliptin and metformin, commonly causes gastrointestinal side effects, including nausea, vomiting, diarrhea, stomach discomfort, and decreased appetite, primarily due to the metformin component. These digestive issues typically improve over time as the body adjusts to the medication. Other common side effects include headache, upper respiratory tract infections, and low blood sugar (hypoglycemia), especially when combined with other diabetes medications. Janumet carries a rare but serious risk of lactic acidosis, a potentially life-threatening condition more likely in patients with kidney problems, liver disease, or excessive alcohol use, as noted in the 2025 standards of care in diabetes 1. The medication may also cause vitamin B12 deficiency with long-term use, as suggested by the Diabetes Prevention Program Outcomes Study (DPPOS) and the need for periodic testing of vitamin B12 levels 1. Some patients experience joint pain or allergic reactions. Taking Janumet with food and starting with a lower dose that gradually increases can help minimize gastrointestinal side effects, as recommended for metformin use in patients with reduced estimated glomerular filtration rates (eGFR) 1. Patients should contact their healthcare provider immediately if they experience severe stomach pain, unusual muscle pain, difficulty breathing, dizziness, or signs of allergic reaction. It is essential to monitor kidney function and adjust the dosage accordingly, especially in older adults, as metformin may be safely used in individuals with an estimated glomerular filtration rate ≥30 mL/min/1.73 m² 1. Regular monitoring of vitamin B12 levels is also crucial for patients on long-term metformin therapy to prevent deficiency and worsening of neuropathy symptoms 1. By understanding these potential side effects and taking appropriate precautions, patients can safely use Janumet to manage their type 2 diabetes while minimizing the risk of adverse effects.

From the Research

Common Side Effects of Janumet

The common side effects of Janumet (sitagliptin and metformin) include:

  • Gastrointestinal complaints such as abdominal pain, nausea, and diarrhea 2
  • Hypoglycemia and body weight gain, although these occur at similar rates compared with placebo 2
  • Digestive side effects and contraindications, such as risk of lactic acidosis in case of renal insufficiency, which are attributable to metformin 3
  • Diarrhea, nausea, and vomiting, with higher incidences observed in patients taking sitagliptin/metformin compared with pioglitazone 4

Less Common Side Effects

Less common side effects of Janumet include:

  • Oedema, with a lower incidence observed in patients taking sitagliptin/metformin compared with pioglitazone 4
  • Hypoglycaemia, with a between-group difference in incidence that did not reach statistical significance 4
  • Late-onset chronic diarrhea, which can occur even after several years of stable metformin therapy 5

Important Considerations

It is essential to note that patients with type 2 diabetes who are taking metformin and experience diarrhea deserve a drug-free interval before undergoing expensive and uncomfortable diagnostic tests, even when the dosage has been stable over a long period 5. Additionally, the tolerance profile of Janumet is rather good, with side effects and contraindications attributable to metformin 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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