Alogliptin / Pioglitazone Side Effects

Medically reviewed by Drugs.com. Last updated on Jan 7, 2025.

Applies to alogliptin / pioglitazone: oral tablet.

Precautions

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

Certain women may be at an increased risk for pregnancy while taking this medicine. If you had problems ovulating and had irregular periods in the past, this medicine may cause you to ovulate. This could increase your chance of becoming pregnant. If you are a woman of childbearing potential, you should discuss birth control options with your doctor.

If you are rapidly gaining weight, having trouble breathing, chest pain or discomfort, extreme tiredness or weakness, irregular breathing, irregular heartbeat, or excessive swelling of the hands, wrist, ankles, or feet, check with your doctor right away. These may be symptoms of heart problems or fluid retention (too much water in the body).

Pancreatitis (swelling or inflammation of the pancreas) may occur while you are using this medicine. Check with your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, loss of appetite, fever, or lightheadedness.

This medicine may cause serious allergic reactions, including anaphylaxis, angioedema, or certain skin conditions (Stevens-Johnson syndrome). These reactions can be life-threatening and require immediate medical attention. Call your doctor right away if you have a rash, itching, blistering, peeling, or loosening of the skin, fever or chills, trouble breathing or swallowing, or any swelling of your hands, face, mouth, or throat while you are using this medicine.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may increase the risk for bone fractures in women. Ask your doctor about ways to keep your bones strong to help prevent fractures.

Using this medicine for a long time may increase your risk for bladder cancer. Tell your doctor right away if you have blood in the urine, a frequent, strong, or increased urge to urinate, painful urination, or pain in the back, lower abdomen, or stomach.

Check with your doctor right away if blurred vision, decreased vision, or any other change in vision occurs while you are taking this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

This medicine may cause hypoglycemia (low blood sugar). Low blood sugar can also occur if you delay or miss a meal or snack, exercise more than usual, drink alcohol, cannot eat because of nausea or vomiting, take certain medicines, or take alogliptin with another type of diabetes medicine (eg, insulin, glimepiride, glipizide, glyburide, or metformin). Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms with low blood sugar. It is important that you learn which symptoms you have in order to treat it quickly. Talk to your doctor about the best way to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your medicine, overeat or do not follow your diet plan, have a fever or infection, or do not exercise as much as usual. High blood sugar can be very serious and must be treated right away. It is important that you learn which symptoms you have in order to treat it quickly. Talk to your doctor about the best way to treat high blood sugar.

There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says you have diabetes with a list of all your medicines.

This medicine may cause severe and disabling joint pain. Call your doctor right away if you have severe joint pain while using this medicine.

This medicine may cause bullous pemphigoid. Tell your doctor if you have large, hard skin blisters while using this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Serious side effects

Along with its needed effects, alogliptin / pioglitazone 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 / pioglitazone:

Other side effects

Some side effects of alogliptin / pioglitazone 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:

For healthcare professionals

Applies to alogliptin / pioglitazone: oral tablet.

General adverse events

The most common side effect reported include nasopharyngitis, back pain and upper respiratory tract infection.^[Ref]

Cardiovascular

Alogliptin:

• Common (1% to 10%): Hypertension, Congestive heart failure (CHF) hospitalization

Pioglitazone:

• Common (1% to 10%): CHF hospitalization
• Postmarketing reports: CHF with and without known heart disease and with and without concomitant insulin^[Ref]

Alogliptin:

In the EXAMINE trial which enrolled patients with type 2 diabetes and recent acute coronary syndrome, more patients (3.9%; n=106) on alogliptin therapy were hospitalized for congestive heart failure (CHF) compare with placebo (3.3%; n=89).

Pioglitazone:

In the PROactive trial, a study in 5238 patients with type 2 diabetes and a history of macrovascular disease who were force-uptitrated to pioglitazone 45 mg once a day or given placebo in addition to standard of care, edema occurred in 27.3% of patients treated with pioglitazone (n=2605) compared with 15.9% of placebo (n=2633) patients. Treatment-emergent adverse events leading to at least 1 hospitalized congestive heart failure event occurred in 5.7% of patients receiving pioglitazone and 4.1% of patients receiving placebo.

The primary objective of the 3-year PROactive trial was to examine the effect of pioglitazone on mortality and macrovascular morbidity in high-risk patients. No statistically significant difference between pioglitazone and placebo/standard care were observed for time to the first occurrence of their first event (all-cause mortality, nonfatal myocardial infarction (MI) including silent MI, stroke, acute coronary syndrome, cardiac intervention including coronary artery bypass grafting or percutaneous intervention, major leg amputation above the ankle, and bypass surgery or revascularization in the leg). A total of 514 patients receiving pioglitazone experienced at least 1 event compared with 572 patients receiving placebo/standard care.

Pioglitazone is associated with edema (peripheral, generalized, and pitting edema and fluid retention) when used alone or when used in combination therapy. In pioglitazone monotherapy trials, edema occurred in 2.5% (n=81), 4.7% (n=275), and 6.5% (n=169) of patients receiving 15 mg, 30 mg, and 45 mg of pioglitazone daily for 16 to 26 weeks. Pioglitazone in combination with a sulfonylurea for 16 to 24 weeks resulted in edema in 1.6% (n=184), 11.3% (n=540), and 23.1% (n=351) of patients receiving 15 mg, 30 mg, and 45 mg of pioglitazone daily, respectively. In a study in patients with NYHA class II or III heart failure the percentage of patients experiencing CHF progression during the study was 13.4% and 8.2% in patients receiving pioglitazone (n=262) and glyburide (n=256), respectively.

Postmarketing reports of congestive heart failure have been received in patients treated with pioglitazone. Reports have been received from patients both with and without a history of a known history of heart disease and both with and without concomitant insulin use.^[Ref]

Endocrine

Alogliptin-Pioglitazone:

• Common (1% to 10%): Hypoglycemia (up to 4.5%)

Alogliptin:

• Common (1% to 10%): Hypoglycemia (up to 5.4%)

Pioglitazone:

• Common (1% to 10%): Hypoglycemia (up to 4.7%)^[Ref]

Gastrointestinal

Alogliptin:

• Uncommon (0.1% to 1%): Pancreatitis (0.2%)
• Postmarketing reports: Acute pancreatitis^[Ref]

Acute pancreatitis was reported in 0.2% (n=6) of patients treated with alogliptin 25 mg and less than 0.1% (n=2) of patients treated with active comparator or placebo in alogliptin clinical trials. IN the EXAMINE trial, a cardiovascular (CV) outcomes trial in patients with type 2 diabetes and high CV risk, acute pancreatitis was reported in 0.4% (n=10) of patients treated with alogliptin and 0.3% (n=7) of patients receiving placebo.^[Ref]

Hematologic

Pioglitazone:

• Uncommon (0.1% to 1%): Elevated ALT (0.3%)
• Frequency not reported: Decreased hemoglobin and hematocrit^[Ref]

Hepatic

Alogliptin:

ALT elevations greater than 3 times upper limit of normal (3 x ULN) occurred in 1.3% of alogliptin treated patients compared with 1.7% of those receiving comparator or placebo during clinical trials. In the EXAMINE trial, a trial in patients with type 2 diabetes and high cardiovascular risk, ALT increases to 3 x ULN occurred in 2.4% of patients receiving alogliptin (compared with 1.8% of placebo patients).

Pioglitazone:

Hepatotoxic effects were not observed in pioglitazone clinical trials, however, postmarketing cases of fatal and nonfatal hepatic failure have been reported.^[Ref]

Alogliptin:

• Postmarketing reports: Hepatic enzyme elevations, fulminant hepatic failure

Pioglitazone:

• Uncommon (0.1% to 1%): Elevated serum alanine aminotransferase (ALT) (0.3%)
• Postmarketing reports: Fatal and non-fatal hepatic fail^[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)^[Ref]

Metabolic

Pioglitazone:

• Frequency not reported: Weight gain, edema
• Postmarketing reports: Rapid increased in weight^[Ref]

Musculoskeletal

Alogliptin-Pioglitazone:

• Common (1% to 10%): Back pain (4.2%)

Alogliptin:

• Common (1% to 10%): Back pain (2%)
• Frequency not reported: Arthralgia

Pioglitazone:

• Common (1% to 10%): Myalgia (5.4%), back pain (3.4%)
• Uncommon (0.1% to 1%): Elevation in serum creatine phosphokinase (CPK) (0.2%)^[Ref]

Alogliptin: 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]

Nervous system

Alogliptin:

• Common (1% to 10%): Headache (4.2%)

Pioglitazone:

• Common (1% to 10%): Headache (9.1%)^[Ref]

Ocular

Pioglitazone:

• Postmarketing reports: Macular edema^[Ref]

Oncologic

Pioglitazone:

• Uncommon (0.1% to 1%): Bladder cancer (up to 0.44%)^[Ref]

The US FDA has released results of its review of pioglitazone and bladder cancer and concluded that the data suggests use of this drug may be linked to an increase risk of bladder cancer. A 10-year prospective cohort study in diabetic patients performed by the manufacturer (n=158,918 never users; n=34,181 ever users) identified 1075 newly diagnosed cases of bladder cancer in never users and 186 cases in ever users. The fully adjusted hazard ratio (HR) showed pioglitazone use was not associated with an increased risk (HR 1.06 (95% confidence interval 0.89 to 1.26). And while a modest trend towards higher risk with increasing duration was observed, this trend was not statistically significant. Compared to the interim 5-year results, the 10-year results found weaker associations that were not statistically significant. However, there are studies that have shown a statistically significant association between exposure to this drug and bladder cancer and an association between cumulative dose or cumulative duration of exposure and bladder cancer. Overall, this drug may be associated with an increase in the risk of urinary bladder tumors, however there is insufficient data to determine whether this drug is a tumor promoter for urinary bladder tumors.^[Ref]

Respiratory

Alogliptin-Pioglitazone:

• Very common (10% or more): Nasopharyngitis (4.9%), upper respiratory tract infection (4.1%)

Alogliptin:

• Common (1% to 10%): Influenza (5.5%), nasopharyngitis (4.7%), upper respiratory tract infection (4.3%)

Pioglitazone:

• Common (1% to 10%): Upper respiratory tract infection (up to 13.2%), sinusitis (6.3%), nasopharyngitis (3.9%)^[Ref]

Dermatologic

Dipeptidyl peptidase-4 inhibitors:

• Postmarketing reports: Bullous pemphigoid

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.

See also:

Further information

Alogliptin/pioglitazone side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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