Short answer: In four pooled trials of alogliptin with pioglitazone, the side effects seen in at least 4% and more often than on either medicine alone or placebo were stuffy or runny nose with sore throat (4.9% vs 3.9% on placebo), back pain (4.2% vs 3.3%) and upper respiratory infection (4.1% vs 3.3%). Oseni has a boxed warning for congestive heart failure from its pioglitazone part. Other risks include swelling, fractures and liver injury.
What Oseni is approved for: Oseni combines alogliptin, a DPP-4 inhibitor, with pioglitazone, a thiazolidinedione. It is approved, along with diet and exercise, to improve blood sugar control in adults with type 2 diabetes (section 1). It is not recommended for type 1 diabetes.
Source
OSENI (alogliptin and pioglitazone) tablets, for oral use, prescribing information and Medication Guide. Takeda Pharmaceuticals America. DailyMed, version published March 24, 2025. DailyMed setid 4c619ed9-fe3e-4158-9938-80c6c3493d55
WARNING: CONGESTIVE HEART FAILURE
Thiazolidinediones, including the pioglitazone in Oseni, cause or worsen congestive heart failure in some people. After starting Oseni and after dose increases, people are watched closely for signs of heart failure such as fast, excessive weight gain, shortness of breath or swelling. If heart failure develops, stopping Oseni or lowering the pioglitazone dose is considered. Oseni is not recommended with symptomatic heart failure, and starting it is contraindicated in established NYHA Class III or IV heart failure.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Oseni.
| Adverse reaction | Alogliptin and pioglitazone N=1533 | Alogliptin N=446 | Pioglitazone N=949 | Placebo N=153 |
|---|---|---|---|---|
| Nasopharyngitis | 75 (4.9) | 21 (4.7) | 37 (3.9) | 6 (3.9) |
| Back Pain | 64 (4.2) | 9 (2.0) | 32 (3.4) | 5 (3.3) |
| Upper Respiratory Tract Infection | 63 (4.1) | 19 (4.3) | 26 (2.7) | 5 (3.3) |
Number of patients (%), pooled from four controlled trials. The combination column pools alogliptin 25 mg and 12.5 mg with pioglitazone 15, 30 and 45 mg. Nasopharyngitis means a stuffy or runny nose with sore throat.
| Event | Placebo N=2,633 | Pioglitazone N=2,605 |
|---|---|---|
| At least one hospitalized congestive heart failure event | 108 (4.1%) | 149 (5.7%) |
| Fatal | 22 (0.8%) | 25 (1%) |
| Hospitalized, nonfatal | 86 (3.3%) | 124 (4.7%) |
Number (%) of patients in PROactive, a trial of pioglitazone in people with type 2 diabetes and blood vessel disease, mean follow-up 34.5 months.
In the four pooled trials, any side effect was reported by 65% on alogliptin with pioglitazone vs 57% on placebo. Stopping for side effects was 2.5% vs 2.0% on placebo, 3.7% on pioglitazone and 1.3% on alogliptin.
Low blood sugar with alogliptin 25 mg plus pioglitazone on metformin: 0.8%, 0% and 3.8% with pioglitazone 15, 30 and 45 mg, vs 0.8% on placebo. With alogliptin 25 mg and pioglitazone 30 mg after diet and exercise alone: 3%.
Pioglitazone alone vs placebo (Table 4): upper respiratory infection 13.2% vs 8.5%, headache 9.1% vs 6.9%, sinusitis 6.3% vs 4.6%, muscle pain 5.4% vs 2.7%, and sore throat 5.1% vs 0.8%.
In people with NYHA class II or early class III heart failure (Table 5), overnight hospital stays for worsening heart failure were 9.9% on pioglitazone vs 4.7% on glyburide, and heart failure progression 13.4% vs 8.2%.
In PROactive, bone fractures in women were 5.1% on pioglitazone vs 2.5% on placebo, mostly of the lower limb and lower arm. There was no increase in men (1.7% vs 2.1%).
In PROactive, bladder cancer was diagnosed in 0.54% on pioglitazone vs 0.19% on placebo. Over 13 years of trial and follow-up, rates did not differ. Observational studies disagree.
Reported after approval, with frequency unknown: for alogliptin, acute pancreatitis, diarrhea, constipation, nausea, ileus, fulminant liver failure, allergic reactions including anaphylaxis and Stevens-Johnson syndrome, severe joint pain, rhabdomyolysis, kidney inflammation and bullous pemphigoid; for pioglitazone, rapid weight gain, swelling, heart failure, new or worse diabetic macular edema, and liver failure.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Congestive heart failure. The boxed-warning risk. Pioglitazone can cause dose-related fluid retention, most often with insulin, which can cause or worsen heart failure. In EXAMINE, 3.9% on alogliptin vs 3.3% on placebo were hospitalized for heart failure. People at risk are watched for symptoms.
Pancreatitis. Acute pancreatitis was reported in 0.2% on alogliptin 25 mg vs under 0.1% on comparators, and in EXAMINE 0.4% vs 0.3% on placebo. Oseni is stopped promptly if it is suspected.
Hypersensitivity reactions. Serious allergic reactions to alogliptin, including anaphylaxis, angioedema and Stevens-Johnson syndrome, have been reported. Oseni is stopped if one is suspected.
Hepatic effects. Fatal and non-fatal liver failure has been reported with pioglitazone or alogliptin. Liver tests are taken before starting and checked promptly if symptoms appear; Oseni is interrupted if ALT is above three times normal and stays abnormal or worsens.
Edema. Swelling was more frequent on pioglitazone than placebo and is dose-related. Oseni is used with caution in people with swelling or at risk of heart failure.
Fractures. Pioglitazone raised fractures in women in PROactive. Fracture risk and bone health are considered, especially in women.
Urinary bladder tumors. Pioglitazone may be linked to bladder tumors. Oseni is not used with active bladder cancer, and benefits and risks are weighed with a past history of bladder cancer.
Low blood sugar with insulin or a sulfonylurea. A lower dose of insulin or a medicine that makes the body release insulin may be needed with Oseni.
Macular edema. Swelling at the back of the eye has been reported with pioglitazone, sometimes with blurred vision. Regular eye exams are advised, and visual symptoms are referred to an eye doctor.
Severe and disabling joint pain. Severe joint pain has been reported with DPP-4 inhibitors, starting from one day to years after starting, and easing after stopping.
Bullous pemphigoid. A blistering skin condition needing hospital care has been reported with DPP-4 inhibitors. Oseni is stopped if it is suspected.
From the Medication Guide that comes with Oseni:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.