Summary

Commonly reported side effects of alogliptin/metformin include: lactic acidosis, nausea, vomiting, and hypoglycemia. Other side effects include: upper respiratory tract infection, abdominal distress, headache, and nasopharyngitis. Continue reading for a comprehensive list of adverse effects.

Applies to alogliptin / metformin: oral tablet.

Serious side effects

Along with its needed effects, alogliptin / metformin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking alogliptin / metformin:

More common

• Blurred vision
• dizziness
• headache
• nervousness
• pounding in the ears
• slow or fast heartbeat

Less common

• Anxiety
• bladder pain
• bloody or cloudy urine
• chest pain or tightness
• chills
• cold sweats
• coma
• confusion
• cool, pale skin
• decreased urine output
• depression
• difficult, burning, or painful urination
• dilated neck veins
• frequent urge to urinate
• increased hunger
• irregular heartbeat
• lower back or side pain
• nausea
• nightmares
• seizures
• shakiness
• slurred speech
• swelling of the face, fingers, feet, or lower legs
• trouble breathing
• unusual tiredness or weakness
• weight gain

Rare

• Blistering, peeling, or loosening of the skin
• bloating
• constipation
• cough
• darkened urine
• diarrhea
• difficulty with swallowing
• fever
• hives or itching
• indigestion
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• pains in the stomach, side, or abdomen, possibly radiating to the back
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• vomiting
• yellow eyes or skin

Incidence not known

• Dark-colored urine
• general feeling of tiredness or weakness
• large, hard skin blisters
• light-colored stools
• redness of the skin
• severe joint pain
• stomach pain, continuing
• swelling of the body

Other side effects

Some side effects of alogliptin / metformin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Body aches or pain
• ear congestion
• loss of voice
• muscle aches
• sneezing
• stuffy or runny nose

Less common

• Back pain

For Healthcare Professionals

Applies to alogliptin / metformin: oral tablet.

General

The most common adverse reactions reported include upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain, and urinary tract infection.^[Ref]

Gastrointestinal

Alogliptin-Metformin:

Common (1% to 10%): Diarrhea, gastroenteritis, abdominal pain, vomiting, gastritis, gastroesophageal reflux disease

Alogliptin:

Common (1% to 10%): Diarrhea, abdominal pain, gastroesophageal reflux disease

Uncommon (0.1% to 1%): Pancreatitis

Postmarketing reports: Acute pancreatitis

Metformin:

Very common (10% or more): Diarrhea (up to 53.2%), Nausea/vomiting (25.5%), flatulence (12.1%)

Common (1% to 10%): Indigestion, abdominal discomfort^[Ref]

Acute pancreatitis has been associated with DPP-4 inhibitors. In a pooled analysis of 13 studies, the overall rate of pancreatitis reported with alogliptin 25 mg, 12.5 mg, active control, or placebo was 2, 1, 1, or 0, events per 1000 patient years, respectively.^[Ref]

Hepatic

Alogliptin:

Postmarketing reports: Hepatic enzyme elevations, fulminant hepatic failure

Metformin:

Very rare (less than 0.01%): Hepatitis, liver function test abnormalities^[Ref]

Cases of hepatic dysfunction including hepatic failure have been received in the postmarketing period with alogliptin-treated patients; causality has not been established.^[Ref]

Metabolic

In metformin-treated patients, lactic acidosis has been reported in approximately 0.03 cases per 1000 patient-years with approximately half these cases resulting in fatalities. In more than 20,000 patient-years exposure in clinical trials, there were no cases of lactic acidosis. Reported cases have occurred primarily in patients with significant renal insufficiency, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications.

In an alogliptin monotherapy study, the incidence of hypoglycemia was 1.5% (compared with 1.6% in placebo). Adding alogliptin to glyburide or insulin did not increase the incidence of hypoglycemia compared with placebo. In elderly patients, the incidence of hypoglycemia was 5.4% with alogliptin compared with 26% for glipizide. In a 26-week, placebo-controlled study of alogliptin once daily as add-on to a metformin regimen, hypoglycemic events were reported in 0.9% of patients in the alogliptin-metformin group compared with 2.9% in the placebo group.^[Ref]

Alogliptin-Metformin:

Common (1% to 10%): Hypoglycemia

Alogliptin:

Common (1% to 10%): Hypoglycemia

Metformin:

Common (1% to 10%): Hypoglycemia, loss of appetite

Very rare (less than 0.01%): Lactic acidosis, vitamin B12 deficiency^[Ref]

Hypersensitivity

Alogliptin:

Uncommon (0.1% to 1%): Hypersensitivity reactions (0.6%)

Postmarketing reports: Anaphylaxis, angioedema, rash, urticaria, severe cutaneous adverse reactions (Stevens-Johnson syndrome), erythema multiforme^[Ref]

Dermatologic

Postmarketing reports of bullous pemphigoid requiring hospitalization have been reported with dipeptidyl peptidase-4 (DPP-4) inhibitors use. These case typically recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP-4 inhibitor.^[Ref]

Alogliptin-metformin:

Common (1% to 10%): Pruritus, rash

Alogliptin:

Common (1% to 10%): Pruritus, rash

Postmarketing reports: Exfoliative skin conditions including Stevens-Johnson syndrome, angioedema, urticaria

Metformin:

Very rare (less than 0.01%): Erythema, pruritus, urticaria

Dipeptidyl peptidase-4 inhibitors:

Postmarketing reports: Bullous pemphigoid^[Ref]

Respiratory

Alogliptin-Metformin:

Common (1% to 10%): Upper respiratory tract infection, nasopharyngitis

Alogliptin:

Common (1% to 10%): Nasopharyngitis, upper respiratory tract infection

Metformin:

Common (1% to 10%): Upper respiratory tract infection, nasopharyngitis^[Ref]

Nervous system

Alogliptin-Metformin:

Common (1% to 10%): Headache

Alogliptin:

Common (1% to 10%): Headache

Metformin:

Common (1% to 10%): Headache, metallic taste^[Ref]

Cardiovascular

In a clinical trial in patients with recent acute coronary syndrome, a greater proportion of patients receiving this drug were hospitalized for congestive heart failure compared with placebo (3.9% [n=106] vs 3.3% [n=89]),^[Ref]

Alogliptin-Metformin:

Common (1% to 10%): Hypertension

Alogliptin:

Common (1% to 10%): Hypertension

Frequency not reported: Heart failure

Metformin:

Common (1% to 10%): Hypertension^[Ref]

Genitourinary

Alogliptin-Metformin:

Common (1% to 10%): Urinary tract infection

Alogliptin:

Common (1% to 10%): Urinary tract infection

Metformin:

Common (1% to 10%): Urinary tract infection^[Ref]

Musculoskeletal

Alogliptin-Metformin:

Common (1% to 10%): Back pain

Alogliptin:

Uncommon (0.1% to 1%): Back pain

Frequency not reported: Arthralgia

Metformin:

Common (1% to 10%): Back pain^[Ref]

Between October 2006 and December 2013, thirty-three cases of severe arthralgia have been reported to the FDA Adverse Event Reporting System Database. Each case involved the use of 1 or more dipeptidyl peptidase-4 (DPP-4) inhibitor. In all cases, substantial reduction in prior activity level was reported, 10 patients were hospitalized due to disabling joint pain. In 22 cases, symptoms appeared within 1 month of starting therapy, in 23 cases symptoms resolved less than 1 month after discontinuation. A positive rechallenge was reported in 8 cases, with 6 cases involving use of a different DPP-4 inhibitor. Sitagliptin had the greatest number of cases reported (n=28) followed by saxagliptin (n=5), linagliptin (n=2), alogliptin (n=1), and vildagliptin (n=2).^[Ref]

Other

Metformin:

Common (1% to 10%): Asthenia^[Ref]