Janumet side effects and how to avoid them

Common Janumet side effects | Diarrhea | B12 deficiency | Serious side effects | Lactic acidosis | Pancreatitis | How long do side effects last? | Warnings | Interactions | How to avoid side effects

Janumet (sitagliptin/metformin) combines two distinct classes of diabetes medication into one pill to treat Type 2 diabetes mellitus. Sitagliptin, available as brand-name Januvia, is a dipeptidyl peptidase-4 (DPP-4) inhibitor that increases glucagon-like peptide 1 (GLP-1) levels to reduce the rise in blood sugar levels after meals. Metformin hydrochloride reduces hepatic (liver) production of glucose and improves peripheral body tissue use of glucose. Janumet is available as a twice-a-day formulation or as a once-a-day formulation called Janumet XR. Part of the attraction to this combination is the lack of weight gain and hypoglycemia (low blood sugar). However, Janumet is not devoid of serious potential side effects.

RELATED: What is Janumet?

Common side effects of Janumet

The following are the most common Janumet side effects:

• Diarrhea or flatulence
• Nausea or vomiting
• Abdominal discomfort (stomach pain), dyspepsia (upset stomach), or indigestion
• Vitamin B12 deficiency
• Asthenia (lack of energy or weakness)
• Headache
• Arthralgia (joint pain)
• Upper respiratory tract infection
• Rash
• Anorexia (loss of appetite)
• Metallic taste
• Ovulation induction

Diarrhea

Diarrhea is the most common side effect of Janumet and derives from the metformin component. Almost 8% of users experienced diarrhea in one study, compared to 4% of those taking placebo (inactive pills used for comparison). In fact, gastrointestinal side effects as a group make up the bulk of the common adverse effects of Janumet. Slowly titrating up on the dose, taking a break from the drug when needed, or switching to an extended-release form could help to alleviate diarrhea from Janumet.

B12 deficiency

In a 29-week clinical trial, about 7% of those using Janumet developed vitamin B12 deficiency. The cause is thought to be metformin-associated impairment of the nutrient’s absorption. Symptoms of low vitamin B12 include anemia, glossitis (swollen and painful tongue), neuropathy (nerve dysfunction), and cognitive slowing. Vitamin supplementation or Janumet stoppage can help to reverse these effects.

Serious side effects of Janumet

• Lactic acidosis
• Megaloblastic anemia (resulting from B12 deficiency)
• Hypersensitivity allergic reactions
• Anaphylaxis (severe life-threatening allergic reaction)
• Angioedema (allergy-related swelling)
• Stevens-Johnson syndrome (severe allergic skin rash with blisters)
• Pancreatitis
• Heart failure
• Acute renal failure (abrupt decline in kidney function)
• Severe arthralgia (severe joint pain)
• Bullous pemphigoid (rash with blisters)
• Rhabdomyolysis (muscle tissue breakdown)

Lactic acidosis

The Food and Drug Administration (FDA) has a black box warning, its highest level label, on Janumet to call attention to the potential for lactic acidosis. The condition is associated with a biochemical imbalance in the bloodstream, with excess lactate leading to acidosis. Symptoms can include malaise (a general ill feeling), abdominal pain, myalgias (muscle pain), somnolence, and trouble breathing. Ultimately, it can result in hypothermia, hypotension (low blood pressure), and death. 

The concern for lactic acidosis with Janumet originates from the metformin component and comes from case reports of this condition occurring in the setting of the medication. The following are some risk factors for lactic acidosis that the FDA has identified: 

• Renal impairment (kidney problems)
• Certain concurrent drugs
• Age 65 or older
• A radiologic study with contrast (intravenous dye)
• Surgery
• Hypoxic (low oxygen) states like congestive heart failure
• Excessive alcohol intake
• Hepatic impairment (liver dysfunction)

Avoiding the use of Janumet in the setting of these risk factors may be necessary, and certainly, if lactic acidosis is suspected and found to be present, the FDA recommends prompt hospital-based treatment and dialysis.

Pancreatitis

Case reports have also surfaced about pancreatitis with the use of sitagliptin. Pancreatitis (inflammation of the pancreas) consists of abdominal pain as the prominent symptom, and fatal cases have occurred among sitagliptin users. However, when clinical trial data was examined, no heightened risk of pancreatitis was seen among sitagliptin users compared to placebo. The concern persists. Janumet should be discontinued, and treatment sought if pancreatitis arises.

How long do Janumet side effects last?

The common gastrointestinal side effects of Janumet may resolve despite medication continuation in a matter of days to weeks, or they may respond to a dose reduction. B12 deficiency can develop over the long term but resolves with supplementation. Others, like arthralgia, may resolve with discontinuation of the drug. The most severe, such as anaphylaxis and lactic acidosis, require emergency treatment in addition to discontinuing the drug. Signs of an allergic reaction to Janumet include shortness of breath, hives, and swelling of the face, lips, tongue, or throat. Seek immediate medical help in the event of an allergic reaction.

Janumet contraindications and warnings

Abuse and dependence

 Janumet is not habit-forming, and discontinuation generates no withdrawal symptoms.

Overdose

The maximum dose of Janumet for most is 50 mg/1000 mg twice daily. An overdose can create dangerous adverse effects, possibly lactic acidosis, so seeking medical attention and calling the Poison Help line at 1-800-222-1222 is appropriate.

Restrictions

• Janumet is not indicated for children. 
• Women who are pregnant or breastfeeding should exert caution and seek medical advice about the possible risks and benefits of Janumet use, principally due to the lack of clinical trial data on sitagliptin use in these situations. 
• A number of medical conditions are contraindications to Janumet use, meaning that Janumet should be avoided. These conditions include:
  • Renal impairment with a glomerular filtration rate (GFR) of less than 30
  • A history of hypersensitivity to the drug
  • Type 1 diabetes mellitus or diabetic ketoacidosis
  • Metabolic or lactic acidosis
  • Hypoxemia (low blood oxygen content)
  • Dehydration
  • Sepsis (a life-threatening condition from infection)
  • Surgery
  • Liver disease
• In addition, Janumet is typically not begun in the setting of kidney disease with a GFR of 30 to 45. 
• Cautious consideration prior to use is worthwhile for anyone with:
  • Congestive heart failure
  • Alcohol abuse
  • A history of pancreatitis
• Based on higher rates of lactic acidosis and conditions which elevate the risk of adverse events, seniors should be more cautious about taking Janumet as well.

Janumet interactions

A lengthy list of medications could interact with Janumet and warrant monitoring or modification of therapy. Other Type 2 diabetes medicines may combine with Janumet to generate hypoglycemia. 

Additional DPP-4 inhibitor drugs should not be used with Janumet. Since DPP-4 inhibitors do not add more diabetic control benefits on top of GLP-1 agonists, the two classes are not used together, and therefore a GLP-1 agonist would not be used with Janumet. 

Some drugs can cause hyperglycemia (high blood sugar) when combined with Janumet. These include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid medications, estrogens, oral contraceptives (birth control), phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.

Most importantly, the following drugs are to be avoided when Janumet is used, due to a heightened risk of lactic acidosis:

• Acetazolamide
• Topiramate
• Risdiplam
• Tafenoquine

How to avoid Janumet side effects

1. Sit down with your healthcare provider before starting Janumet and follow up regularly while taking the drug. Review your list of prescription medication, over-the-counter drugs, and supplements to check for drug interactions. Go over your history of medical conditions to look for any contraindications to Janumet use.
2. Take Janumet with meals. Take the medication exactly as directed.
3. If a dose is missed and you remember soon after it was due, you can take it, but if the next dose is coming soon, skip the missed dose. Do not take an extra dose to make up for a missed dose.
4. Swallow the tablet whole, and do not chew, break, or crush it. Refer to the medication guide for more instructions on how to take Janumet.
5. Avoid dehydration by drinking enough fluids.
6. Check with the prescribing healthcare professional to see if your vitamin B12 level should be monitored.
7. Ask the prescriber if you should monitor your blood glucose levels. Understand the signs of hypoglycemia, such as weakness, sweating, shakiness, anxiety, fast heartbeat, irregular heartbeat, blurred vision, tiredness, and confusion. Have sugary drinks or food available to take in case hypoglycemia is experienced. Discuss the signs of hypoglycemia and the response to it with family, friends, and co-workers so that they may assist you if needed.
8. Check with your healthcare provider to know when you should temporarily stop Janumet. Possible examples of these instances would be around the time of surgery or when you are not eating or drinking well, are experiencing excessive diarrhea, have a serious infection, are consuming alcohol, or have had a radiologic study with contrast material (intravenous dye).
9. Do not drink alcohol.

For more drug information, contact your healthcare provider, a pharmacist, or refer to the drug manufacturer, Merck.

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