Nesina (alogliptin) is an oral DPP-4 inhibitor approved by the FDA in January 2013 for type 2 diabetes. It lowers A1C by 0.5 to 0.8 percent with weight neutrality and low hypoglycemia risk on monotherapy. The defining trial — EXAMINE in post-acute coronary syndrome patients — showed cardiovascular safety but a small heart failure hospitalization signal, leading to a 2016 FDA heart failure warning shared with saxagliptin. Renal dose adjustment is required across three tablet strengths (25, 12.5, 6.25 mg). Combinations with metformin (Kazano) and pioglitazone (Oseni) extend its dosing options.
What Nesina Is
- Generic name: alogliptin
- Drug class: DPP-4 inhibitor (gliptins)
- Manufacturer: Takeda
- FDA approval: January 2013
- Forms: 6.25, 12.5, and 25 mg tablets
- Combinations: Kazano (with metformin), Oseni (with pioglitazone)
How Nesina Works
Alogliptin inhibits the enzyme DPP-4, which normally breaks down the incretin hormones GLP-1 and GIP. By blocking that breakdown, Nesina raises endogenous incretin levels, leading to:
- Glucose-dependent insulin secretion from the pancreas
- Suppression of glucagon secretion
- Mild slowing of gastric emptying
- Minimal direct effect on appetite or weight
Because the mechanism is glucose dependent, hypoglycemia is rare when Nesina is used alone.
Approved Use
Nesina is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It can be used:
- As monotherapy
- Combined with metformin (Kazano), sulfonylureas, thiazolidinediones, or insulin
- As part of Oseni (alogliptin plus pioglitazone)
Not approved for type 1 diabetes or DKA.
Dosing
| Setting | Dose | Notes |
|---|---|---|
| Standard adult, eGFR ≥ 60 | 25 mg once daily | With or without food |
| eGFR 30–59 | 12.5 mg once daily | Moderate CKD |
| eGFR < 30 or dialysis | 6.25 mg once daily | Severe CKD |
| Hepatic impairment | Use with caution | Limited data in severe disease |
| Pregnancy | Not recommended | Insufficient data |
EXAMINE — What the Trial Showed
EXAMINE (White et al., NEJM 2013) enrolled 5,380 patients with type 2 diabetes who had experienced an acute coronary syndrome within the prior 15 to 90 days. Results:
- Primary 3-point MACE endpoint: non-inferior to placebo (HR 0.96)
- Heart failure hospitalization: HR 1.19 in post-hoc analysis (smaller than saxagliptin’s 1.27)
- All-cause mortality: no significant difference
- Acute pancreatitis: small numerical increase, not statistically significant
- Hypoglycemia: similar to placebo on monotherapy, increased with sulfonylurea or insulin
FDA response: heart failure warning added to the Nesina label in April 2016 along with Onglyza. Practical implications:
- Avoid in patients with established heart failure
- Use caution in patients with high heart failure risk
- Prefer linagliptin or sitagliptin for DPP-4 therapy in heart failure
- Stop if heart failure develops on treatment
Benefits
- A1C reduction of 0.5 to 0.8 percent depending on dose and baseline
- Weight neutral
- Low hypoglycemia risk on monotherapy
- Once-daily oral dosing
- Three tablet strengths allowing renal-adjusted dosing
- Useful combinations (Kazano with metformin, Oseni with pioglitazone)
- Generally well tolerated
Common Side Effects
| Side Effect | Approximate Frequency |
|---|---|
| Nasopharyngitis | ~4% |
| Headache | ~4% |
| Upper respiratory tract infection | ~4% |
| Hypoglycemia (with SU or insulin) | variable |
| Diarrhea or abdominal pain | 2–3% |
| Back pain | ~3% |
| Rash | ~2% |
Rare but Serious Side Effects
- Heart failure hospitalization — ~19% increase in EXAMINE; FDA warning 2016
- Acute pancreatitis — class signal; stop for severe abdominal pain
- Severe joint pain — FDA class warning 2015
- Bullous pemphigoid — rare blistering autoimmune skin reaction
- Hepatic enzyme elevation — rare hepatic failure reports
- Hypersensitivity — angioedema, urticaria, anaphylaxis
- Stevens-Johnson syndrome — very rare reports
Hepatic Considerations
Nesina has been associated with rare hepatic enzyme elevation and very rare hepatic failure reports. Practical approach:
- Check baseline liver function (ALT, AST, alkaline phosphatase, bilirubin)
- Repeat if symptoms suggest liver issues (fatigue, jaundice, dark urine, right upper quadrant pain)
- Discontinue if ALT or AST greater than 3 times upper limit of normal without explanation
- Avoid in severe hepatic impairment
Drug Interactions
- Sulfonylureas and insulin: increased hypoglycemia risk — reduce partner drug
- No major CYP450 interactions (alogliptin is mostly excreted unchanged)
- Renal-altering drugs (NSAIDs, ACE/ARB, diuretics): monitor eGFR for dose adjustment
Nesina Combinations
| Brand | Components | Dosing |
|---|---|---|
| Nesina | Alogliptin 6.25, 12.5, or 25 mg | Once daily |
| Kazano | Alogliptin + metformin | Twice daily with meals |
| Oseni | Alogliptin + pioglitazone | Once daily |
How Nesina Compares with Other DPP-4 Inhibitors
| Feature | Nesina | Tradjenta | Onglyza | Januvia |
|---|---|---|---|---|
| FDA approval | 2013 | 2011 | 2009 | 2006 |
| Standard dose | 25 mg daily | 5 mg daily | 5 mg daily | 100 mg daily |
| Renal adjustment | Yes | No | Yes | Yes |
| HF signal | Yes (small) | No | Yes (larger) | No |
| CV trial | EXAMINE | CARMELINA | SAVOR-TIMI 53 | TECOS |
| Three tablet strengths | Yes | No | Two | Three |
Who Should Avoid Nesina
- Heart failure or high heart failure risk
- Prior pancreatitis (relative contraindication, class-wide)
- Severe hepatic impairment
- Type 1 diabetes
- DKA
- Known hypersensitivity to DPP-4 inhibitors
- Pregnancy or breastfeeding
Monitoring on Nesina
- A1C every 3 months until stable, then every 6 months
- eGFR at baseline and every 6 to 12 months (or sooner with risk factors)
- Liver function at baseline and periodically; sooner if symptoms
- Symptoms of heart failure, joint pain, abdominal pain at every visit
- Skin check for new blistering or unusual rash
Practical Notes for Users
- Take at the same time each day, with or without food
- If kidney function changes, dose may need adjustment
- Tell every prescriber and dentist you take Nesina
- Report new or worsening shortness of breath, swelling, or rapid weight gain
- Stop and seek evaluation for severe abdominal pain
- Report new severe joint pain
- Report new yellow eyes or skin, dark urine, or right upper abdomen pain — possible liver issue
Related Reading
For the broader class see the DPP-4 inhibitors list. Compare with other DPP-4 agents at Onglyza (saxagliptin) and Tradjenta (linagliptin). For pioglitazone context (relevant to Oseni combination) see pioglitazone (Actos). For broader context see our treatment overview and A1C levels. External: the EXAMINE trial and the ADA Standards of Care.
The Bottom Line
Nesina (alogliptin) is a once-daily oral DPP-4 inhibitor that lowers A1C by 0.5 to 0.8 percent with weight neutrality and low hypoglycemia risk on monotherapy. The EXAMINE trial in post-ACS patients showed cardiovascular safety but a smaller heart failure hospitalization signal than saxagliptin, prompting a 2016 FDA heart failure warning. Three tablet strengths (25, 12.5, 6.25 mg) allow renal dose adjustment across all CKD stages. Combinations Kazano (with metformin) and Oseni (with pioglitazone) provide multimechanism oral therapy. Most clinicians choose Nesina when DPP-4 inhibition is appropriate but heart failure risk is absent — and prefer linagliptin or sitagliptin when heart failure is in the picture.
