title: Saxagliptin versus glipizide as add-on therapy to metformin: assessment of hypoglycemia.
abstract: OBJECTIVE
  To compare characteristics of hypoglycemic episodes in patients with type 2 diabetes receiving saxagliptin or glipizide add-on therapy to metformin.
  
  
  METHODS
  This was a post hoc analysis of an international, randomized, parallel-group, double-blind, active-controlled, phase 3 trial. The 52-week trial and 52-week extension were conducted from December 2007 to August 2010. Patients aged ≥18 years with glycated hemoglobin (HbA1c) >6.5% to 10.0% receiving stable metformin doses (≥1500 mg/d) were randomized 1:1 to add-on therapy with saxagliptin 5 mg/d or glipizide 5 to 20 mg/d (titrated to optimal effect or highest tolerable dose during the initial 18 weeks). Hypoglycemic episodes were recorded in patient diaries. Confirmed hypoglycemic events were defined as fingerstick glucose ≤50 mg/dL (≤2.8 mmol/L) with associated symptoms.
  
  
  RESULTS
  Of 858 patients randomized, 428 received saxagliptin + metformin, and 430 received glipizide + metformin. Saxagliptin was noninferior to glipizide in lowering HbA1c. Hypoglycemia with saxagliptin + metformin and glipizide + metformin was reported by 15 (24 events) and 165 (896 events) patients, respectively, through week 104. The mean (SD) number of hypoglycemic events per patient reporting hypoglycemia was lower with saxagliptin + metformin versus glipizide + metformin through weeks 52 (1.5 [SD 0.88] vs 4.8 [SD 4.9], respectively) and 104 (1.6 [SD 0.99] vs 5.4 [SD 5.8]). Most patients receiving glipizide + metformin with hypoglycemia had multiple events (124/165 patients [75%]). Confirmed hypoglycemia, major events, and severe events occurred only with glipizide + metformin. Time to first hypoglycemic event was shorter with glipizide versus saxagliptin. Limitations of this analysis include its post hoc nature, a high rate of study discontinuation, and exclusion of patients with serious comorbidities and complications.
  
  
  CONCLUSIONS
  Saxagliptin + metformin was associated with fewer patients reporting hypoglycemia and fewer and less severe hypoglycemic events in those experiencing hypoglycemia compared with glipizide + metformin. ClinicalTrials.gov registration number: NCT00575588.
authors.affiliation: George Washington University School of Medicine , Washington, DC , USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Mintz
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Minervini
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005913:Glipizide / Q000008:administration & dosage*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane; D005913:Glipizide