Janumet (sitagliptin/metformin) for type 2 diabetes: a patient's guide

Janumet is an oral prescription medication designed to treat type 2 diabetes. It combines two active ingredients, sitagliptin phosphate and metformin. These medications work in tandem to enhance blood sugar control in adults with type 2 diabetes by increasing insulin sensitivity and decreasing glucose production in the liver. Janumet is often prescribed when diet and exercise alone do not suffice and may also be recommended for managing atherosclerotic cardiovascular disease.*

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Manage type 2 diabetes with convenient online doctor visits

At PlushCare, we provide expert diabetes management care with our board-certified physicians. Telemedicine allows for regular monitoring of your diabetes with flexible, convenient online doctor visits. You can report blood sugar levels, discuss symptoms, and receive feedback through virtual consultations. Your doctor can also remotely prescribe and adjust your type 2 diabetes medications, such as Janumet. Our doctors also provide holistic health advice for diabetes care, including diet, exercise, and healthy lifestyle changes.

How does Janumet work? Understanding the mechanism of action

Together, sitagliptin and metformin help lower blood sugar levels more effectively than either medication alone, especially after meals. Combined, these medicines have a complementary effect on type 2 diabetes management.

Sitagliptin, also known by the brand name Januvia, belongs to a class of drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors. It works by increasing levels of incretins, hormones that help to regulate blood sugar, particularly after eating. Incretins help increase insulin production when needed and reduce the liver's sugar production when not required. Other DPP-4 inhibitors include Tradjenta (linagliptin), Onglyza (saxagliptin), and Nesina (alogliptin).

Metformin is in the class of medications called biguanides. It works by decreasing the amount of sugar produced by the liver and reducing the amount of sugar absorbed by the intestines. Metformin also helps to improve the body's response to insulin. Metformin is also known by the brand names Axpinet, Diagemet, Glucient, Glucophage, and Metabet, among others. Other medications containing metformin include Invokamet (canagliflozin/ metformin) and Xigduo XR (dapagliflozin/metformin).

How to take Janumet

Aim to be consistent with the timing of your Janumet medication each day. Take the tablets whole with a glass of water without crushing, chewing, or breaking them. The medication is usually taken twice daily, but follow your doctor’s instructions.

  • Janumet dosages

    You should discuss any concerns or questions about dosage with your prescribing physician. Janumet is available in different strengths and ratios. 

    • Janumet tablets: The tablet strength indicates each tablet's amount of sitagliptin/metformin. Typical dosages may involve taking one or two tablets daily, usually with meals, to ensure optimal absorption and reduce the risk of gastrointestinal side effects. Janumet tablets come in different strengths: 

      • Janumet (sitagliptin 50 mg/metformin 500 mg)

      • Janumet (sitagliptin 50 mg/metformin 1000 mg)

      • Janumet (sitagliptin 100 mg/metformin 1000 mg)

    • Janumet XR: Janumet XR is an extended-release formulation, allowing for once-daily dosing. This extended-release feature allows for a gradual release of the active ingredients throughout the day, providing a more consistent and sustained effect on blood sugar levels. The tablet strength (e.g., 100 mg/1000 mg) indicates the sitagliptin/metformin content. The usual recommendation is to take Janumet XR with your evening meal. The convenience of a once-daily regimen may make it easier to stick with the treatment. Janumet XR also comes in varying strengths: 

      • Janumet XR (sitagliptin 100 mg/metformin HCl 1000 mg)

      • Janumet XR (sitagliptin 50 mg/metformin HCl 500 mg)

      • Janumet XR (sitagliptin 50 mg/metformin HCl 1000 mg)

    • Maximum dose: The maximum recommended dose of Janumet is typically determined by the healthcare provider based on the patient's response to treatment and individual factors. Always adhere to the prescribed dosage and administration instructions provided by your doctor.

    • Missed dose: If you miss your dose, don’t double up on the next dose. Instead, continue with your regular dosing schedule.

    • Timing: The timing of taking Janumet can depend on the specific formulation. For Janumet XR, an extended-release formulation, taking the medication with your evening meal is often recommended to ensure a consistent release of the active ingredients throughout the day. For other formulations, the general guideline is to take Janumet with meals to maximize absorption and reduce the likelihood of gastrointestinal side effects.

    • Nighttime intake: While taking Janumet XR with your evening meal is recommended due to its extended-release mechanism, the timing for other formulations during the day can vary. Following your healthcare provider's instructions for the specific prescription is essential.

    • Before or after food: Janumet is typically taken with meals to synchronize its effects with food intake. This helps optimize the medication's action on blood sugar levels and reduces the risk of gastrointestinal side effects.

  • Monitoring and follow-up

    If you are prescribed sitagliptin, it is crucial to maintain regular monitoring and follow-up appointments with your doctor. These appointments are opportunities to assess the medication's effectiveness, address any concerns, and make necessary adjustments to your diabetes management plan. Your doctor will guide you on the necessary monitoring procedures, which may include:

    • Blood sugar levels: Regular monitoring of blood sugar levels is fundamental in evaluating the effectiveness of sitagliptin. Your doctor may recommend specific times for checking blood sugar, and the results will inform adjustments to your treatment plan.

    • Hemoglobin A1c tests: Periodic hemoglobin A1c tests provide a broader picture of your average blood sugar levels over time. These tests help assess the overall effectiveness of diabetes management, including the impact of sitagliptin.

    • Kidney function tests: Sitagliptin, like other diabetes medications, may require monitoring of kidney function. Your doctor may order kidney function tests to ensure the medication is well-tolerated and does not adversely affect your kidneys.

    • Follow-up appointments: These will allow for ongoing assessment of your response to sitagliptin. During these appointments, your doctor can address any side effects, discuss lifestyle factors, and make necessary adjustments to optimize your diabetes care.

    • Symptom improvement: Reducing diabetes symptoms, such as excessive thirst, frequent urination, and fatigue, may indicate effective medication management.

    • New or worsening symptoms: The emergence of new or worsening diabetes symptoms may prompt a reassessment of your medication regimen to ensure optimal management.

Janumet side effects, warnings, and precautions

Janumet and Janumet XR may elicit certain side effects, with some being more prevalent than others. While these effects are typically temporary, lasting from a few days to weeks, it is crucial to consult your doctor or pharmacist if they persist, cause discomfort, or worsen in severity.

  • Common side effects

    Janumet may come with some common mild, temporary side effects.

  • Warnings and precautions for specific patient groups

    Who should not use Janumet:  

    • Type 1 diabetics: You should not use Janumet if you have type 1 diabetes, as it has not been studied to show benefit or be safe for this condition. 

    • History of pancreatitis: Do not take Janumet if you’ve had pancreatitis before, as it can increase the risk of repeat episodes.

    • Pregnant patients: Janumet should only be used when needed, with the potential benefits justifying potential risks to the fetus. Approval from your OBGYN would be necessary before starting.

    • Nursing mothers: Sitagliptin phosphate/metformin is not recommended for lactating mothers.

    Caution should be used in the following when considering Janumet: 

    • Elderly patients: Caution is advised when prescribing Janumet to elderly patients due to a potentially higher risk of renal impairment.

    • Patients with a history of heart failure (CHF): Several types of DPP4 inhibitors other than Janumet have been associated with worsening CHF. Talk to your doctor about your history before making a shared decision about using Janumet.

    • X-ray tests that use contrast agents: Janumet should be temporarily stopped before such tests and restarted only after assessing kidney function as they may temporarily impair kidney function.

    • Patients with liver problems:  The medication should also be used cautiously in patients with liver problems, necessitating regular monitoring of liver function.

    • Alcohol: Caution is advised when consuming alcohol with Janumet, as it can potentiate the risk of lactic acidosis.

  • Serious side effects

    Rare but severe side effects associated with Janumet include pancreatitis, allergic reactions, kidney issues, and joint pain. Stomach pains, nausea, vomiting, and other gastrointestinal symptoms, or any other unusual or severe symptoms, should be promptly reported to your doctor for a thorough evaluation. Patients should also be alert for the rare but severe condition of lactic acidosis associated with metformin, a component of Janumet.

    A severe notable side effect linked to Janumet is hypothermia, particularly when used in conjunction with specific medications, marked by a dangerously low body temperature. Patients must be attuned to symptoms like shivering, confusion, or drowsiness and seek immediate medical attention if such signs emerge. 

    Additionally, cases of hypotension (low blood pressure) and resistant bradyarrhythmias (slow heart rate) have been reported, particularly in those with pre-existing cardiovascular conditions. Patients with a history of heart issues should be closely monitored, and any signs of dizziness, fainting, or irregular heart rhythms should be promptly communicated to a healthcare professional.

What are the pros and cons?



  • Effective blood sugar control: Janumet helps lower blood sugar levels.

  • Dual mechanism of action: The combination of sitagliptin (a DPP-4 inhibitor) and metformin provides a dual mechanism of action, offering a comprehensive approach to managing blood sugar levels.

  • Increased insulin: as a DPP-4 inhibitor, Sitagliptin increases insulin production in response to elevated blood sugar levels.

  • Convenient: Janumet's combination therapy, with both sitagliptin and metformin in a single pill, is easy for patients to take once daily.

  • Potential weight benefits: Janumet is less likely to cause weight gain compared to some other diabetes medications. In certain cases, it may even contribute to modest weight loss.


  • Risk of common side effects: Common side effects associated with Janumet include nausea, diarrhea, and other gastrointestinal issues, primarily attributed to metformin. 

  • Rare but serious side effects: Janumet carries a severe but rare risk of lactic acidosis, especially in patients with kidney problems. While lactic acidosis is uncommon, its severity requires close monitoring and awareness.

  • Not suitable for everyone: Janumet is not recommended for individuals with certain conditions, particularly those with severe liver or kidney disease. 

  • Risk of hypoglycemia when combined with other medications: When used along with other diabetes medications, Janumet may heighten the risk of hypoglycemia (low blood sugar).

  • Monitoring: Like many diabetes medications, using Janumet requires regular monitoring of blood sugar levels and kidney function.

Frequently asked questions (FAQs)

  • How long does it take for Janumet to work?

    The onset of action for Janumet (sitagliptin/metformin) can vary due to its two components. Metformin can start working within hours to reduce blood sugar, while sitagliptin has a more gradual effect through boosting incretin hormones, reaching its full potential within 4-8 weeks. The overall full effect of Janumet can take several days to weeks and varies depending on individual factors. Monitoring blood sugar levels regularly during the initial weeks and adjusting the dosage as needed under your doctor's guidance is essential.

  • Is sitagliptin/metformin the same as Janumet?

    Sitagliptin/metformin is a combination of sitagliptin and metformin, and Janumet is one of the brand names for this combination medication. The combination aims to address different aspects of glucose regulation in people with type 2 diabetes.

  • Is it safe to eat grapefruit while taking Janumet?

    Grapefruit can interact with certain medications by affecting their metabolism in the body. However, there is no well-documented interaction between grapefruit and Janumet. It's always prudent to consult a healthcare provider about specific dietary considerations and potential medication interactions.

  • What is the difference between Janumet and Janumet XR?

    The primary difference lies in the formulation and dosing frequency. Janumet XR is an extended-release version, allowing for once-daily dosing. Regular Janumet may require more frequent dosing throughout the day. Both formulations combine sitagliptin and metformin for the management of type 2 diabetes.

  • How much does a 30-day supply of Janumet cost?

    Janumet costs about $720 for 60 tablets of 50 mg/1000 mg at the full retail price. With twice-daily dosing, 60 tablets is only enough medicine for a 30-day supply. Insurance coverage may vary, and the price may be significantly higher or lower depending on what your insurance will pay for. Janumet therapy could cost almost $9,000 for people without health insurance coverage.

  • Why is Janumet so expensive?

    Various factors, including research and development expenses, production costs, and market demand, can influence the cost of Janumet. Additionally, brand-name medications can be more expensive than generic alternatives. Your doctor may recommend assistance programs, generic options, or alternative medications.

  • Is Janumet bad for the kidneys?

    Janumet, particularly its metformin component, can pose risks for patients with impaired kidney function. Before starting Janumet, doctors assess kidney function, which may be contraindicated in severe cases. Lower doses and regular monitoring are crucial to ensure the medication's safety in patients with compromised renal function.

  • What is the difference between Janumet 50/500 and 50/1000?

    The numbers in Janumet (e.g., 50/500 and 50/1000) refer to the dosage of sitagliptin (in milligrams) and metformin (in milligrams) per tablet. The first number represents the sitagliptin dosage, and the second number represents the metformin dosage. For example, Janumet 50/500 contains 50 mg of sitagliptin and 500 mg of metformin.

  • Can Janumet (sitagliptin/metformin) cause weight gain?

    Janumet generally does not cause weight gain or weight loss. While individual responses can vary, Janumet is not typically associated with weight gain, making it a good choice for patients concerned about weight management.

  • Does Janumet 50/1000 cause weight loss?

    Weight changes with Janumet can vary. While some may experience weight stability, others may observe a small amount of weight loss. Diet, exercise, and individual metabolic responses can influence weight changes.

  • What’s the difference between sitagliptin vs. vildagliptin?

    Sitagliptin and vildagliptin are dipeptidyl peptidase-4 (DPP-4) inhibitors used in managing type 2 diabetes. The critical difference lies in their chemical structures; individual responses may vary. Healthcare providers choose between them based on patient factors, efficacy, and tolerability.

How to get Janumet online

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Talk to your doctor online about your type 2 diabetes symptoms.

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PlushCare is dedicated to providing you with accurate and trustworthy health information.

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  2. Janumet. Accessed on December 14, 2023 at https://www.janumetxr.com/janumet-side-effects/

  3. HIVinfo. “HIV and Lactic Acidosis”  Accessed on December 14, 2023 at https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-lactic-acidosis

  4. National Center for Biotechnology Information. "Management of patients with risk factors" Accessed on December 14, 2023 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884537/

  5. Janumet. Accessed on December 14, 2023 at https://www.janumetxr.com/

  6. National Center for Biotechnology Information. "Sitagliptin/Metformin (Janumet) as Combination Therapy In the Treatment of Type-2 Diabetes Mellitus" Accessed on December 14, 2023 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541863/

  7. National Center for Biotechnology Information. "Oral and Injectable (Non-Insulin) Pharmacological Agents for the Treatment of Type 2 Diabetes" Accessed on December 14, 2023 at https://www.ncbi.nlm.nih.gov/books/NBK279141/

  8. National Center for Biotechnology Information. "Pharmacokinetic comparison of sitagliptin and metformin HCl extended-release tablets versus JANUMET® XR in healthy volunteers under fasting and fed conditions" Accessed on December 14, 2023 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073488/

  9. MedlinePlus. Accessed on December 14, 2023 at https://medlineplus.gov/druginfo/meds/a606023.html#

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