Pharmacological Class:
Dipeptidyl peptidase-4 (DPP-4) inhibitor.

Active Ingredient(s):
Alogliptin 6.25mg, 12.5mg, 25mg; tabs.

Company
Takeda Pharmaceuticals North America, Inc.
Indication(s):
As adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM).
Limitations of use: not for treatment of type 1 diabetes or diabetic ketoacidosis.

Pharmacology:
Alogliptin acts by slowing the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner.

Clinical Trials:
Nesina has been studied as monotherapy and in combination with metformin, a sulfonylurea, a thiazolidinedione (either alone or in combination with metformin or a sulfonylurea), and insulin (either alone or in combination with metformin).

A total of 8,673 patients with T2DM were randomized in 10 double-blind, placebo- or active-controlled clinical studies conducted to eva luate the effects of Nesina on glycemic control.

Three of the ten studies eva luated Nesina in 1,768 patients with T2DM that had inadequate glycemic control on diet and exercise. All three studies had a 4-week, single-blind, placebo run-in period followed by a 26-week randomized treatment period.

In the first study, 329 patients were randomized to Nesina 12.5mg, Nesina 25mg, or placebo once daily. The Nesina 25mg treatment group demonstrated statistically significant improvements compared to placebo from baseline in A1C (−0.6% vs. 0%) and fasting plasma glucose (FPG; −16mg/dL vs. 11mg/dL; P<0.01 for both) at Week 26.

In the second study, 655 patients were randomized to Nesina 25mg, pioglitazone 30mg, Nesina 12.5mg + pioglitazone 30mg, or Nesina 25mg + pioglitazone 30mg once daily. Coadministration of Nesina 25mg + pioglitazone 30mg resulted in statistically significant improvements from baseline in A1C (−1.7%) and FPG (−50mg/dL) compared to Nesina 25mg alone (−1.0% and −26mg/dL, respectively) and pioglitazone 30mg alone (−1.2% and −37mg/dL, respectively; P<0.01 compared to individual component regimens) at Week 26.

In the third study, 784 patients were randomized to placebo, metformin HCl 500mg or metformin HCl 1000mg twice daily, Nesina 12.5mg twice daily or Nesina 25mg daily; Nesina 12.5mg + metformin HCl 500mg or metformin HCl 1000mg twice daily. Both coadministration arms resulted in statistically significant improvements in A1C and FPG when compared to their respective individual alogliptin and metformin component regimens. Coadministration treatment arms also showed improvements in 2-hour postprandial glucose compared to Nesina or metformin alone.

For information on studies conducted in add-on combination therapy: see full labeling.

Legal Classification:
Rx

Adults:
25mg once daily. Renal impairment: moderate (CrCl ≥30–<60mL/min): 12.5mg once daily; severe (CrCl ≥15–<30mL/min) or ESRD (CrCl <15mL/min or need hemodialysis): 6.25mg once daily.

Children:
Not established.

Warnings/Precautions:
Monitor for signs/symptoms of pancreatitis; discontinue if suspected. History of angioedema with other DPP-4 inhibitors. Discontinue if serious hypersensitivity reaction is suspected. Hepatic impairment. Obtain liver function tests before starting therapy; interrupt and eva luate if liver enzymes elevated or abnormal tests persist; do not restart if liver injury is confirmed and no other etiology can be found. Monitor renal function prior to therapy and periodically thereafter. Pregnancy (Category B). Nursing mothers.

Interaction(s)
Concomitant sulfonylurea or insulin: may need lower dose of sulfonylurea or insulin to reduce risk of hypoglycemia.

Adverse Reaction(s)
Nasopharyngitis, headache, upper respiratory tract infection.

How Supplied:
6.25mg—30, 90; 12.5mg, 25mg—30, 90, 500