Metformin and Ibuprofen

Metformin and Ibuprofen

How ibuprofen works on inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). Ibuprofen is a generic name for a drug containing the same name active ingredient. It is used as a pain reliever for various conditions such as: headaches, dental pain, muscle pain, tendinitis (inflammation or irritation of a tendon, a thick cord that attaches bone to muscle), menstrual cramps, and for the treatment of pain, swelling and joint stiffness caused by arthritis, osteoarthritis, juvenile arthritis, bursitis, ankylosing spondylitis, psoriatic arthritis and gout. It can also be used to temporarily reduce fever and for the treatment of common cold symptoms. Ibuprofen may be used intravascular with opiates for relieving moderate to severe pain. Ibuprofen lysine may be also used intravscular as a therapy for premature neonates with ductus arteriosus.

Ibuprofen is available in following dosage forms and strengths: capsule, capsule liquid filled, capsule coated (200, 220 and 400 mg), injection (100mg/ml), oral liquid (100 mg/5mL and 50 mg/1.25mL), solution (100 mg, 100 mg/5mL), suspension (100 mg, 200 mg/10mL, 100 mg/5mL) and tablet (200, 300, 400, 600 and 800 mg).

Common Brand names for ibuprofen are: Advil, Motrin, Brufen, Calprofen, Genpril, Ibu, Midol, Nuprin, Cuprofen, Nurofen, Ibuprofen 800 and PediaCare Children’s Pain Reliever/Fever Reducer IB.

 Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID)

How does Metformin and Ibuprofen work in the body?

Metformin reduces glucose levels in blood by decreasing the hepatic glucose production and intestinal glucose absorption, and by improving cell sensitivity to insulin by increasing peripheral uptake of glucose and utilization. These effects are mediated by the initial activation of AMP-activated protein kinase which is a liver enzyme that plays a significant role in insulin signalization, energy balance, and the metabolism of glucose and lipids. Activation of AMP- protein kinase is needed for inhibitory effect of metformin on liver cell production. Increased peripheral utilization of glucose is caused by improved insulin binding to its receptors. Metformin administration also increases AMP- protein kinase in skeletal muscle cells. AMP- protein kinase is known to cause deployment of GLUT-4 to the cell plasma membrane, which results in insulin-independent glucose uptake. The rare side effect called lactic acidosis can be caused by decreased liver uptake of lactate, which is one of the substrates of gluconeogenesis. Patients who have healthy renal function, the slight excess are simply cleared. However, patients who have severe renal impairment the accumulation of lactic acid can be clinically significant. Conditions such as severe hepatic disease and acute/decompensated heart failure may precipitate lactic acidosis.


Ibuprofen inhibits synthesis of prostaglandins (substances in the body that play a key role in pain and inflammation processes in body tissues) by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2. Inhibition of COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects while the inhibition of COX-1 may cause gastrointestinal bleeding and ulcers. Ibuprofen has the lowest risk of causing gastrointestinal bleeding of all NSAID, producing balanced inhibitory effects on both COX-1 and COX-2 isoenzymes. But, this advantage is lost at high doses. This drug may also inhibit chemotaxis, decrease proinflammatory cytokine activity, alter lymphocyte activity, and inhibit neutrophil aggregation – these effects may also contribute to anti-inflammatory activity.

Can patients take Metformin and Ibuprofen together?

Patients with diabetes should not use Metformin and Ibuprofen together without medical advice. Ibuprofen can put a strain on kidneys function, which could already be happening because of patient’s diabetes. The best and safer option for painkilling is acetaminophen (Tylenol). If acetaminophen is not working patients with diabetes on metformin therapy may be able to use an NSAID, but they should always check with their doctor first to ensure that their kidneys are functioning well.

The table below shows the incidence of side effects after Metformin and Ibuprofen administration in recommendable doses. The incidence can be increased if these drugs are taken together or overdosed.

Frequency not defined Asthenia, Diarrhea, Flatulence, Weakness, Myalgia, Upper respiratory tract infection, Hypoglycemia, GI complaints, Lactic acidosis (rare), Low serum vitamin B-12, Nausea/vomiting, Chest discomfort, Chills, Dizziness, Abdominal distention, Constipation, Heartburn, Dyspepsia, Nasopharyngitis, Headache, Peripheral edema, Pharyngitis, Osteoarthritis, Epigastric pain, Rash, Tinnitus, Edema, Fluid retention

Does Metformin have interaction with Grapefruit juice?

Many substances that can be found in grapefruit, and grapefruit juice can affect the absorption and effectiveness of the drugs used at the same time. Grapefruit juice can decrease levels of certain drugs in blood making them ineffective and in some rare cases it can have the opposite effect by increasing the drug concentrations in blood and putting patients at risk of having too much of their medicine in bloodstream. Metformin is also known to have food interactions, that can have a negative impact on the body, however grapefruit is not one of them.

Studies on humans have not found any relevant interaction between grapefruit and Metformin. However, one study on rats showed that this combination can raise the concentration of lactic acid in the rats, causing the lowering of pH levels in the body and thus negatively affecting the metabolism. As this result has not been reproduced, general opinion is that it is not recommended that people should cut grapefruit intake completely while they are on a grapefruit therapy, until relevant clinical studies prove opposite.

Special precautions and warnings Metformin and Ibuprofen administration:

  • Before taking Metformin, patients should tell their doctor or pharmacist if they are allergic to metformin; or if they have any other allergies. Products with metformin may contain inactive ingredients that can cause allergic reactions or other problems.
  • Before using Metformin, patients should tell their doctor or pharmacist their medical history, especially if they ever had or have: breathing problems such as obstructive lung disease and asthma, blood problems such as anemia or vitamin B12 deficiency, kidney or liver disease.
  • Patients using Metformin should tell their doctors that they are using metformin before having surgery or any X-ray scanning procedure that use injectable iodinated contrast material.
  • Patients on a Metformin therapy may experience blurred vision, drowsiness or dizziness, or due to extremely low or high blood sugar levels. They should not drive, use machinery, or do any activity that requires alertness or clear vision until they are sure that they can perform such activities safely.
  • Patients using Metformin should limit the usage of alcohol while using this medication because alcohol can increase the risk of lactic acidosis and low blood sugar can be developed.
  • High fever, diuretic such as hydrochlorothiazide, too much sweating, prolonged diarrhea, and vomiting may cause dehydration and increase the risk of lactic acidosis. Patients should stop taking metformin and tell their doctor if they have prolonged diarrhea or vomiting.
  • It may be harder to control your blood sugar when your body is stressed (such as due to fever, infection, injury, or surgery). Consult your doctor because increased stress may require a change in your treatment plan, medications, or blood sugar testing.
  • Geriatric patients on Metformin therapy may be at higher risk for side effects such as low blood sugar or lactic acidosis.
  • Pregnant patients should use Metformin only when it is clearly needed. Patients should discuss the risks and benefits with their doctor. Doctor may direct to use insulin instead of metformin during pregnancy.
  • Metformin can make changes in the menstrual cycle, such as promote ovulation and this drug may also increase the risk of becoming pregnant.
  • Metformin can pass into breast milk, but only in small amounts. Patients should consult their doctor before breast-feeding.
  • Patients using Ibuprofen should tell their doctor if they have or have ever had any of following conditions such as: asthma, frequent stuffed or runny nose or nasal polyps, swelling of the inside of the nose, swelling of the arms, feet, ankles, hands, or lower legs; lupus or liver or kidney disease.
  • Patients using Ibuprofen should mention to their doctor if they are using following drugs: ACE inhibitors such as: enalapril , fosinopril, lisinopril, benazepril, captopril, moexipril, diuretics lithium and methotrexate. Doctor may need to change the doses of these medications or monitor more carefully for side effects.
  • Patients should not take nonprescription ibuprofen with any other analgesic unless doctor tells that should.
  • If patients are giving ibuprofen to a child, it is important to tell the child’s doctor if the child has not been drinking fluids or has lost a large amount of fluid from repeated vomiting or diarrhea.

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About Miljan Krcobic 78 Articles
My name is Miljan Krčobić. I was born on 14th of November 1989. in Negotin, Serbia, where I finished elementary and high school. In June 2015 I graduated from the Faculty of Pharmacy in Belgrade and thus acquired the title Master of Pharmacy. From the July of 2015 to January 2016 I worked in a pharmaceutical company Hemofarm a.d.(Member of STADA group) based in Vrsac, Serbia, as an expert associate for GMP compliance within the sector Quality Assurance. I am currently working in a pharmacy called Zivkovic in Negotin. As a freelancer I write medical articles on Elance and Upwork.