Alogliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor in the management of type 2 diabetes mellitus (T2DM). DATA SOURCES: Searches were conducted in MEDLINE (1946-August 2013) and Embase (1974-August 2013) for English language articles using key words alogliptin, SYR-332, Nesina, Oseni, and Kazano. References of articles were reviewed to identify any additional sources. STUDY SELECTION AND DATA EXTRACTION: Articles with adequate sample sizes, evaluating clinically relevant end points were included. DATA SYNTHESIS: Alogliptin is a highly selective and potent competitive inhibitor of DPP-4. The DPP-4 enzyme rapidly inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. GLP-1, which releases postprandial insulin in response to meals, is thought to be deficient in patients with T2DM. Studies evaluating the role of alogliptin in T2DM have shown significant reductions in blood glucose and hemoglobin A1C (A1C) levels. Alogliptin doses of 12.5 to 25 mg once daily reduced A1C by 0.56% to 0.59% as monotherapy. Patients given alogliptin in addition to other antidiabetic agentsexperienced additional A1C lowering of 0.4% to 0.8%. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections, and headache. Alogliptin demonstrates a neutral effect on weight. A large trial evaluating the cardiovascular safety of alogliptin is currently being conducted. CONCLUSIONS: Alogliptin is the fourth DDP-4 inhibitor approved in the US for the treatment of T2DM. It is available alone (Nesina) and in fixed-dose combinations with metformin (Kazano) and pioglitazone (Oseni). It has no demonstrable advantages over other agents in its class.

Evaluating the analgesic efficacy of administering celecoxib as a component of multimodal analgesia for outpatient anterior cruciate ligament reconstruction surgery.

BACKGROUND: Cyclooxygenase-2 inhibitors may play an important role in multimodal management of pain after orthopedic surgery. We examined the analgesic efficacy of administering celecoxib as a component of a multimodal analgesic regimen for outpatient anterior cruciate ligament (ACL) surgery. METHODS: Two-hundred consecutive patients were randomized to receive acetaminophen 1000 mg and either celecoxib 400 mg or placebo 1-2 h before ACL surgery. All patients received intraarticular analgesics (bupivacaine, clonidine, and morphine) and had an external cooling system applied to the operative knee. After discharge, patients were instructed to take acetaminophen 1000 mg every 6 h and either celecoxib 200 mg every 12 h or matching placebo for the first 14 days postoperatively. Oxycodone 5-10 mg was available for rescue analgesia. RESULTS: Patients in the celecoxib group were more likely to experience less pain in the recovery room (P < 0.01) and require less opioids (P < 0.001) for postoperative analgesia. These patients reported a lower incidence of postoperative nausea and vomiting (P < 0.05) and were discharged home earlier (P < 0.05). While at home, patients in the celecoxib group reported lower pain scores both at rest (P < 0.05) and with movement (P < 0.01), and used less oxycodone at all postoperative time intervals. CONCLUSIONS: The perioperative administration of celecoxib decreases postoperative pain, opioid use, postoperative nausea and vomiting, and recovery room length of stay. These results support the use of celecoxib as a component of a preventive multimodal analgesic technique for ACL surgery.