Dipeptidyl peptidase-4 (DPP-4) inhibitor + thiazolidinedione.
Alogliptin, pioglitazone; 12.5mg/15mg, 12.5mg/30mg, 12.5mg/45mg, 25mg/15mg, 25mg/30mg, 25mg/45mg; tabs.
As adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) when treatment with both alogliptin and pioglitazone is appropriate.
Limitations of use: not for treatment of type 1 diabetes or diabetic ketoacidosis.
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. Pioglitazone activates peroxisome proliferator-activated receptor-gamma, thereby improving insulin sensitivity in muscle and adipose tissue while inhibiting hepatic gluconeogenesis.
The coadministration of alogliptin and pioglitazone has been studied in patients with T2DM inadequately controlled on either diet and exercise alone or on metformin alone. A total of 655 patients inadequately controlled on diet and exercise alone were evaluated in a 26-week, double-blind, active-controlled study. Patients were randomized to alogliptin 25mg alone, pioglitazone 30mg alone, alogliptin 12.5mg + pioglitazone 30mg, or alogliptin 25mg + pioglitazone 30mg once daily.
Coadministration of alogliptin 25mg + pioglitazone 30mg resulted in statistically significant improvements from baseline in A1C (−1.7%) and fasting blood glucose (FPG; −50mg/dL) compared to either alogliptin 25mg (−1% and −26mg/dL, respectively) or pioglitazone 30mg (−1.2% and −37mg/dL, respectively; P<0.01 compared to individual component regimens) alone at Week 26.
For information on all other studies conducted: see full labeling.
Swallow whole; do not split tabs. Take once daily with or without food. Inadequately controlled on diet/exercise, or on metformin or alogliptin monotherapy: initially 25mg/15mg or 25mg/30mg daily. Previously on pioglitazone alone: initially 25mg/15mg, 25mg/30mg, or 25mg/45mg daily. Switching from alogliptin with pioglitazone: start at dose based on current therapy. NYHA Class I or II HF: initially 25mg/15mg. All: max 25mg/45mg daily. Renal impairment: moderate (CrCl ≥30–<60mL/min): 12.5mg/15mg, 12.5mg/30mg, or 12.5mg/45mg daily; severe or ESRD: not recommended. Concomitant gemfibrozil or other strong CYP2C8 inhibitors: max pioglitazone 15mg daily.
NYHA Class III or IV heart failure.
Symptomatic HF: not recommended. Risk of CHF; monitor after initiation and dose increases; consider discontinuation or reduce pioglitazone dose if occurs. Monitor for pancreatitis or serious hypersensitivity reaction; discontinue if suspected. History of angioedema with other DPP-4 inhibitors. Renal impairment; monitor prior to starting therapy and periodically thereafter. Hepatic impairment; obtain LFTs before starting therapy; interrupt and evaluate if liver enzymes elevated; do not restart if liver injury is confirmed and no other etiology can be found. Active bladder cancer: do not use. Do regular eye exams. Resumption of premenopausal ovulation in anovulatory women may occur (may result in unintended pregnancy). Pregnancy (Category C); use adequate contraception. Nursing mothers: not recommended.
Concomitant insulin may cause fluid retention. Potentiated by strong CYP2C8 inhibitors (eg, gemfibrozil). Antagonized by CYP2C8 inducers (eg, rifampin). Concomitant sulfonylurea or insulin: may need lower dose of sulfonylurea or insulin to reduce risk of hypoglycemia.
Nasopharyngitis, back pain, upper respiratory tract infection; edema, fractures (esp. females), macular edema.
Tabs—30, 90, 500