# Alogliptin
**Alogliptin** is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus. It is not indicated for type 1 diabetes or diabetic ketoacidosis.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) Developed by [Takeda Pharmaceutical Company](https://www.edgepedia.org/takeda-pharmaceutical-company) under the code SYR-322, it was first approved in the United States on January 25, 2013, as Nesina, alongside two fixed-dose combinations.[2](https://www.drugs.com/history/nesina.html) • [3](https://www.takeda.com/en-us/newsroom/news-releases/2013/takeda-receivesr-for-three-new-type-2-diabetes-therapies-nesina/)
| Key fact | Detail |
|---|---|
| Drug class and use | DPP-4 inhibitor, adjunct to diet and exercise for glycemic control in adults with type 2 diabetes; not for type 1 diabetes or diabetic ketoacidosis[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) |
| US approval | January 25, 2013 (Nesina, Takeda; development code SYR-322)[2](https://www.drugs.com/history/nesina.html) |
| Standard dose | 25 mg once daily with normal renal function or mild impairment; 12.5 mg if creatinine clearance is 30 to <60 mL/min; 6.25 mg if severe impairment or end-stage renal disease[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) |
| Mechanism | Slows inactivation of the incretin hormones, increasing their bloodstream concentrations and lowering fasting and postprandial glucose in a glucose-dependent manner[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) |
| Fixed-dose combinations | With metformin (Kazano in the US, Vipdomet in the EU) and with pioglitazone (Oseni in the US, Incresync in the EU)[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4090041/) • [5](https://www.ema.europa.eu/en/medicines/human/EPAR/vipdomet) |
| Cardiovascular outcomes | EXAMINE trial in 5,380 patients with type 2 diabetes and recent acute coronary syndrome showed noninferiority for major adverse cardiac events, with an upper 95% confidence limit of 1.16 against the FDA threshold of 1.3[6](https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2013/10/06/21/16/EXAMINE) |
| Common adverse reactions | Nasopharyngitis, headache, and upper respiratory tract infection (each ≥4% and more frequent than placebo)[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) |
## Mechanism of action
Alogliptin inhibits DPP-4, the enzyme that rapidly degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). By slowing this inactivation, the drug raises circulating incretin concentrations, which enhances pancreatic insulin secretion and suppresses glucagon secretion, lowering glucose in a glucose-dependent manner.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) • [7](https://www.nejm.org/doi/abstract/10.1056/NEJMoa1305889) In healthy subjects, a single dose produces peak DPP-4 inhibition within two to three hours.[8](https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203414s005lbl.pdf)
The drug is primarily excreted by the kidneys, and cytochrome P450-related metabolism is negligible; no significant interactions were observed with the CYP substrates, inhibitors, or renally excreted drugs tested.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) This renal elimination underlies the dose adjustments for impaired kidney function.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91)
## Dosing and formulations
The recommended dose is 25 mg once daily, taken with or without food, in patients with normal renal function or mild impairment (creatinine clearance ≥60 mL/min). For moderate renal impairment (creatinine clearance 30 to <60 mL/min) the dose is 12.5 mg once daily, and for severe impairment (15 to <30 mL/min) or end-stage renal disease, including hemodialysis, it is 6.25 mg once daily; tablets may be taken without regard to dialysis timing. Renal function should be assessed before starting therapy and periodically thereafter.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91)
Tablets are supplied in 25 mg, 12.5 mg, and 6.25 mg strengths.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) Fixed-dose combinations pair alogliptin with metformin (Kazano; Vipdomet in Europe, containing 12.5 mg alogliptin with 850 or 1,000 mg metformin, taken twice daily) and with pioglitazone (Oseni; Incresync in Europe).[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4090041/) • [5](https://www.ema.europa.eu/en/medicines/human/EPAR/vipdomet) The metformin combination is taken twice daily with food, with a maximum daily dose of 25 mg alogliptin and 2,000 mg metformin hydrochloride.[9](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203414Orig1s000ClinPharmR.pdf)
## Clinical efficacy
Alogliptin has been studied as monotherapy and as add-on or fixed-dose combination therapy with metformin, pioglitazone, sulfonylureas such as glyburide, and insulin.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4090041/) In a 26-week placebo-controlled study of patients inadequately controlled on pioglitazone (with or without metformin or a sulfonylurea), mean HbA1c reductions from baseline were 0.66% with alogliptin 12.5 mg, 0.8% with 25 mg, and 0.19% with placebo (P<0.001 for both alogliptin doses); fasting plasma glucose fell by about 20 mg/dL with either alogliptin dose versus 5.7 mg/dL with placebo.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4090041/) In the same study, 49.2% of patients on 25 mg alogliptin reached an HbA1c of 7.0% or below, compared with 34.0% on placebo (p = 0.004).[10](https://www.medicines.org.uk/emc/product/5234/smpc)
**Triple therapy.** In a 26-week trial of 1,554 participants uncontrolled on at least 1,500 mg/day of metformin, adding both alogliptin and pioglitazone produced a mean HbA1c reduction of 1.4%, versus 0.9% for adding pioglitazone alone (P<0.001). Hyperglycemic rescue was needed by 1.5% to 4.6% of triple-therapy patients versus 8.5% to 14.7% of those on dual therapy.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4090041/) A 52-week study found that adding 25 mg alogliptin to 30 mg pioglitazone plus metformin gave HbA1c improvements that were both noninferior and statistically superior to up-titrating pioglitazone to 45 mg plus metformin.[10](https://www.medicines.org.uk/emc/product/5234/smpc)
Hypoglycemia rates were low across regimens: in the monotherapy study, 1.5% with alogliptin versus 1.6% with placebo, and add-on use with glyburide or insulin did not increase hypoglycemia versus placebo. In a 52-week comparison in elderly patients, hypoglycemia occurred in 5.4% on alogliptin versus 26% on glipizide.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91)
In pediatrics, a phase 1 dose-finding study (SYR-322-104) and a phase 3 study (SYR-322-309) were conducted; the phase 3 study did not demonstrate efficacy of alogliptin versus placebo, either as monotherapy or as add-on to metformin, and no pediatric efficacy claim was sought.[11](https://www.fda.gov/media/172956/download) • [12](https://www.fda.gov/media/172957/download)
## EXAMINE cardiovascular outcomes trial
The [EXAMINE trial](https://www.edgepedia.org/examine-trial) (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) tested cardiovascular safety in a very high-risk population: 5,380 patients with type 2 diabetes randomized within 15 to 90 days of an acute coronary syndrome (myocardial infarction or unstable angina requiring hospitalization) to alogliptin or placebo added to existing therapy.[7](https://www.nejm.org/doi/abstract/10.1056/NEJMoa1305889) The trial met its noninferiority objective for major adverse cardiac events, with an upper 95% confidence limit of 1.16, below the 1.3 threshold set by the FDA for postmarketing trials. Individual endpoints were similar between arms: cardiovascular death 3.3% versus 4.1%, myocardial infarction 6.9% versus 6.5%, and all-cause mortality 5.7% versus 6.5%.[6](https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2013/10/06/21/16/EXAMINE)
**Heart failure.** Because excess heart failure hospitalizations had been reported with another DPP-4 inhibitor, EXAMINE investigators analyzed this outcome separately. Hospital admission for heart failure occurred in 3.9% of alogliptin patients versus 3.3% on placebo (HR 1.19, 95% CI 0.90–1.58) over a median follow-up of 533 days, and the composite of cardiovascular death or heart failure hospitalization was 7.4% versus 7.5%.[13](https://pubmed.ncbi.nlm.nih.gov/25765696/) • [6](https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2013/10/06/21/16/EXAMINE) A post hoc analysis found the risk of cardiovascular death and heart failure hospitalization similar between arms overall (HR 1.00, 95% CI 0.82–1.21) and in patients with heart failure at baseline (HR 0.90, 95% CI 0.70–1.17).[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC5216099/) Baseline factors associated with heart failure hospitalization in the trial included a history of heart failure (28% of the population), elevated NT-proBNP, prior myocardial infarction, baseline insulin use, and severe kidney impairment.[15](https://www.annualreviews.org/doi/pdf/10.1146/annurev-med-050214-013431) The incidences of hypoglycemia, pancreatitis, pancreatic cancer, and angioedema were similar between the two arms.[6](https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2013/10/06/21/16/EXAMINE)
## Safety and warnings
The US prescribing information carries warnings for acute pancreatitis (reported postmarketing and in trials; 0.2% on alogliptin 25 mg versus <0.1% on comparators in glycemic trials, and 0.4% versus 0.3% in EXAMINE), heart failure, serious hypersensitivity reactions including anaphylaxis, angioedema, and Stevens-Johnson syndrome, hepatic failure, severe and disabling arthralgia, and bullous pemphigoid requiring hospitalization.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) A history of serious hypersensitivity to alogliptin-containing products is a contraindication.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) When alogliptin is combined with insulin or a sulfonylurea, a lower dose of the secretagogue or insulin may be needed to reduce hypoglycemia risk.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91)
Across 14 controlled trials involving 14,778 patients, the overall adverse reaction incidence was 73% with alogliptin 25 mg versus 75% with placebo, and discontinuation for adverse reactions was 6.8% versus 8.4%.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91) The label states that no clinical study has established conclusive evidence of macrovascular risk reduction with alogliptin or any other antidiabetic drug.[1](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91)
## Regulatory history
Takeda's new drug applications for alogliptin and the alogliptin/pioglitazone fixed-dose combination received a Complete Response Letter from the FDA in April 2012; the company resubmitted in July 2012, and approval of Nesina and the two combination products followed on January 25, 2013.[2](https://www.drugs.com/history/nesina.html) • [3](https://www.takeda.com/en-us/newsroom/news-releases/2013/takeda-receivesr-for-three-new-type-2-diabetes-therapies-nesina/) In the European Union the drug is marketed as Vipidia, with the combinations Vipdomet (with metformin) and Incresync (with pioglitazone); a 2025 [European Medicines Agency](https://www.edgepedia.org/european-medicines-agency) pharmacovigilance committee assessment concluded that the benefit-risk balance of these products remains favorable in their approved indications.[5](https://www.ema.europa.eu/en/medicines/human/EPAR/vipdomet) • [16](https://www.ema.europa.eu/system/files/documents/minutes/minutes-prac-meeting-24-november-27-november-2025-publication_en.pdf)
## References
1. [Alogliptin Tablets, Highlights of Prescribing Information, DailyMed (NIH)](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a05d6d17-79f9-4788-a4d5-467bca1a2d91)
2. [Nesina FDA Approval History, Drugs.com](https://www.drugs.com/history/nesina.html)
3. [Takeda Receives FDA Approval for Three New Type 2 Diabetes Therapies, January 25, 2013](https://www.takeda.com/en-us/newsroom/news-releases/2013/takeda-receivesr-for-three-new-type-2-diabetes-therapies-nesina/)
4. [Holland and Neumiller (2014). Alogliptin in combination with metformin and pioglitazone for the treatment of type 2 diabetes mellitus. Dovepress/PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4090041/)
5. [Vipdort: European public assessment report summary, European Medicines Agency](https://www.ema.europa.eu/en/medicines/human/EPAR/vipdomet)
6. [EXAMINE trial summary, American College of Cardiology](https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2013/10/06/21/16/EXAMINE)
7. [White WB et al. Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes. New England Journal of Medicine](https://www.nejm.org/doi/abstract/10.1056/NEJMoa1305889)
8. [Alogliptin tablet label (2015), FDA](https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203414s005lbl.pdf)
9. [NDA 203414 Clinical Pharmacology Review, SYR-322MET, FDA](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203414Orig1s000ClinPharmR.pdf)
10. [Alogliptin/Metformin Hydrochloride 12.5 mg/1000 mg tablets, Summary of Product Characteristics, eMC](https://www.medicines.org.uk/emc/product/5234/smpc)
11. [Statistical Review, pediatric study SYR-322-309, FDA](https://www.fda.gov/media/172956/download)
12. [Office of Clinical Pharmacology Review, pediatric program, FDA](https://www.fda.gov/media/172957/download)
13. [Zannad F et al. Heart failure and mortality outcomes in EXAMINE. The Lancet (PubMed)](https://pubmed.ncbi.nlm.nih.gov/25765696/)
14. [Cardiovascular Safety of Incretin-Based Therapies in Type 2 Diabetes, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5216099/)
15. [Cardiovascular Effects of Incretin-Based Therapies, Annual Review of Medicine](https://www.annualreviews.org/doi/pdf/10.1146/annurev-med-050214-013431)
16. [Minutes of PRAC meeting 24–27 November 2025, European Medicines Agency](https://www.ema.europa.eu/system/files/documents/minutes/minutes-prac-meeting-24-november-27-november-2025-publication_en.pdf)
---
*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Cardiovascular, metabolic, and endocrine drugs › Metabolic and endocrine drugs › Antidiabetic drugs*
*Initially written Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license