Onglyza and Kombiglyze XR Side Effects

Onglyza and Kombiglyze XR can cause several minor, common side effects such as nausea, headaches and respiratory infections. These occurred in at least 5 percent of people in clinical trials. But postmarketing reports show more rare, but serious side effects such as heart failure and pancreatitis.

Onglyza 5mg Pills
Onglyza and Kombiglyze XR Side Effects
  1. Black Box Warning Lactic acidosis (Kombiglyze XR only)
  2. Most reported side effect in clinical trials Upper respiratory tract infection for Onglyza (7.7 percent of 882 people in clinical trials) and headache for Kombiglyze XR (7.5 percent of 320 clinical trial participants)
  3. Side effect reported most often to the FDA Congestive heart failure (270 reports)

Onglyza and Kombiglyze XR are oral medications that treat Type 2 diabetes. Kombiglyze XR combines the active ingredient in Onglyza, saxagliptin, with metformin extended release.

The most common side effects of these two drugs are respiratory and urinary tract infections, headache, diarrhea and nausea. In general, common side effects occurred in 5 percent or more of clinical trial participants.

Common side effects include:
  • Headache
  • Diarrhea
  • Urinary tract infections
  • Upper respiratory tract infection
  • Stomach pain
  • Bloating
  • Sore throat
  • Nausea
  • Runny nose
  • Cough

The drugs’ labels include information about these side effects based on data gathered from five clinical trials with 882 participants.

The patients — primarily white adults with an average age of 55 years — took saxagliptin for about 21 weeks. More people who took the higher dose of 5 mg suffered side effects and dropped out of clinical trials.

In addition to clinical trial data, manufacturer AstraZeneca reported side effects data gathered from postmarketing reports. Postmarketing data comes from patients who use the drug once it is on the market.

Patients and doctors report side effects to the U.S. Food and Drug Administration’s Adverse Events Reporting System (FAERS). One important thing to note is that FAERS is a voluntary reporting system and can’t verify whether the drug actually caused the side effect. The FDA also says it’s possible for a drug to cause more problems than people report.

Did You Know?
Taking Onglyza with another antidiabetic drug may increase side effects. For example, hypoglycemia occurred more often in people who combined Onglyza with another diabetes drug or insulin.
Source: Onglyza prescribing information

FAERS received 3,927 reports of Onglyza adverse events from 2009 to Sept. 30, 2018, including 242 deaths. Gastrointestinal and cardiac disorders topped the list of most-reported health issues.

Along with the common side effects, studies and postmarketing reports link saxagliptin to serious side effects such as heart failure, pancreatitis and severe joint pain. Kombiglyze XR also has a black box warning for lactic acidosis, a condition where toxic lactic acid builds up in the blood.

Saxagliptin and Heart Failure

In April 2016, the FDA released a Drug Safety Communication warning about an increased risk of heart failure with saxagliptin. The agency required the makers of Onglyza and Kombiglyze XR to add warnings to the medication labels.

“A U.S. Food and Drug Administration (FDA) safety review has found that Type 2 diabetes medicines containing saxagliptin and alogliptin may increase the risk of heart failure, particularly in patients who already have heart or kidney disease,” the FDA said. “As a result, we are adding new warnings to the drug labels about this safety issue.”

The FDA studied clinical trial data that showed more people who took saxagliptin or alogliptin — a similar drug — ended up in the hospital for heart failure than those who took a placebo. For saxagliptin, the risk was about 35 patients out of every 1,000.

Although Onglyza may increase the risk of heart failure, the risk may not be as high as with other diabetes drugs.  A large cohort study of more than 376,000 patients found the risk of being hospitalized for heart failure was lower among saxagliptin users than among patients who used pioglitazone (brand name Actos) or long-acting insulin treatment.

Author Sengwee Toh and colleagues published the results in April 2016 in the Annals of Internal Medicine. They used records collected by 18 data partners to look at adults with Type 2 diabetes who started taking the drugs between 2006 and 2013. They concluded more research is needed to better understand the risk.

Some people who suffered heart failure and other heart problems filed Onglyza lawsuits claiming the drug’s maker did not properly warn of the risk.

Risk of Acute Pancreatitis

Onglyza and other medications in the same class called dipeptidyl peptidase-4 (DPP-4) inhibitors carry warnings for an increased risk of pancreatitis.

Postmarketing reports show a small number of people who took Onglyza suffered acute pancreatitis. The drug’s label cautions that patients should be “observed carefully” for signs of the condition after starting the drug.

Researchers conducting a trial confirmed definite acute pancreatitis in 0.2 percent of participants who took Onglyza compared to 0.1 percent of people who received the placebo. About 88 percent of the Onglyza users and all of the placebo-treated participants had pre-existing risk factors for pancreatitis.

Fact
According to Onglyza’s label, 17 out of 8,240 people who received Onglyza during a trial suffered pancreatitis versus 9 out of 8,173 who received placebo.
Source: Onglyza prescribing information

Practical Diabetes published the case report of a 33-year-old man who suffered acute pancreatitis after he started taking Onglyza and then switched to Kombiglyze XR. He went to the hospital complaining of dizziness, vomiting, palpitations and breathlessness.

Doctors performed tests and found fluid around the pancreas and swelling. The tail of the pancreas also had dying tissue. They diagnosed him with acute pancreatitis. After they replaced Kombiglyze XR with insulin and metformin, the patient went home in stable condition.

Severe and Disabling Joint Pain (Arthralgia)

Some patients reported severe and disabling joint pain after taking Onglyza, Kombiglyze XR or other DPP-4 inhibitors. This side effect is rare, but in 2015, the FDA required drugmakers to place warnings on the medication inserts.

The agency had analyzed postmarketing reports submitted between Oct. 16, 2006 and Dec. 31, 2013 and found five reports of joint pain associated with saxagliptin, according to a 2015 Drug Safety Communication.

As of Sept. 30, 2018, the number had risen to 41 reports of arthralgia for Onglyza and 13 reports of arthralgia for Kombiglyze XR in FAERS. Twenty-three reported cases were serious and three involved deaths.

“Patients should not stop taking their DPP-4 inhibitor medicine, but should contact their health care professional right away if they experience severe and persistent joint pain.”

Source: U.S. Food and Drug Administration

“Patients should not stop taking their DPP-4 inhibitor medicine, but should contact their health care professional right away if they experience severe and persistent joint pain,” the FDA said in 2015. “Health care professionals should consider DPP-4 inhibitors as a possible cause of severe joint pain and discontinue the drug if appropriate.”

Symptoms may occur any time after beginning treatment. People who reported joint pain said their symptoms started anywhere from one day to one year after starting the drug, according to Onglyza’s insert. The pain went away after the patients stopped taking the drug — typically in less than 30 days. But in some patients, the pain came back once they started therapy again.

Case ‘Important’ in Bringing Attention to Potential Side Effect, Doctors Say

Dr. Akshay C. Dahiwele and colleagues reported a rare case of knee arthralgia caused by saxagliptin in the September-October 2016 edition of International Journal of Basic & Clinical Pharmacology.

A 55-year-old woman with Type 2 diabetes had already been taking 2,000 mg of metformin a day when her doctor added 5 mg of saxagliptin to her daily regimen. After two months of taking saxagliptin, she reported pain in both her knees.

Doctors ruled out osteoarthritis, gout and other types of possible joint pain. They discontinued saxagliptin, and the symptoms improved.

“We consider that this case is important in bringing this potential side effect to the attention of both pharmacologists and primary care physicians,” the authors wrote.

Please seek the advice of a medical professional before making health care decisions.

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Michelle Llamas, Senior Content Writer
Written By Michelle Llamas Senior Writer

Michelle Llamas has been writing articles and producing podcasts about drugs, medical devices and the FDA for seven years. She specializes in fluoroquinolone antibiotics and products that affect women’s health such as Essure birth control, transvaginal mesh and talcum powder. Michelle collaborates with experts, including board-certified doctors, patients and advocates, to provide trusted health information to the public. Some of her qualifications include:

  • American Medical Writers Association (AMWA) Engage Committee and Membership Committee member
  • Centers for Disease Control and Prevention (CDC) Health Literacy certificates
  • Original works published or cited in The Lancet, British Journal of Clinical Pharmacology and the Journal for Palliative Medicine
Edited By
Medically Reviewed By
Dr. John A. Daller
Dr. John A. Daller American Board of Surgery

10 Cited Research Articles

  1. U.S. Food and Drug Administration. (2015, August). Highlights of Prescribing Information; Onglyza (saxagliptin) tablets, for oral use. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022350s016lbl.pdf
  2. DailyMed. (2018, April 19). Onglyza – saxagliptin tablet, film coated. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5116390-e0fe-4969-94cb-e9de5165fbab&audience=professional#s5.1
  3. DailyMed. (2017, February 27). Kombiglyze XR – saxagliptin and metformin hydrochloride tablet, film coated, extended release. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fbd25da4-ebe6-45c9-beb8-93523d11a0b4&audience=consumer#section-6.1
  4. U.S. Food and Drug Administration. (2015, August 28). FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. Retrieved from https://www.fda.gov/downloads/Drugs/DrugSafety/UCM460038.pdf
  5. U.S. Food and Drug Administration. (2016, April 5). FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. Retrieved from https://www.fda.gov/Drugs/DrugSafety/ucm486096.htm
  6. Dahiwele, A. et al. (2016). Saxagliptin induced bilateral knee arthralgia: a rare case report. Retrieved from http://www.ijbcp.com/index.php/ijbcp/article/view/679
  7. AstraZeneca. (n.d.). Possible side effects of Onglyza. Retrieved from https://www.onglyza.com/side-effects.html.
  8. U.S. Food and Drug Administration. (n.d.). FDA Adverse Event Reporting System (FAERS) Public Dashboard. Retrieved from https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/surveillance/adversedrugeffects/ucm070093.htm
  9. Alajaj, A. & Elrishi, M.A. (2016). Acute pancreatitis associated with saxagliptin treatment presented by metabolic acidosis. Retrieved from https://www.practicaldiabetes.com/wp-content/uploads/sites/29/2016/06/Acute-pancreatitis-associated-with-saxagliptin-treatment-presented-by-metabolic-acidosis.pdf
  10. Toh, S. et al. (2016). Risk for Hospitalized Heart Failure Among New Users of Saxagliptin, Sitagliptin, and Other Antihyperglycemic Drugs. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178978/
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