Saxagliptin versus glipizide as add-on therapy to metformin: assessment of hypoglycemia

• Published in: Current medical research and opinion Vol. 30; no. 5; pp. 761 - 770
• Main Authors: Mintz, Matthew L., Minervini, Gianmaria
• Format: Journal Article
• Language: English
• Published: Colchester Informa UK Ltd 01-05-2014; Taylor & Francis; Informa
• Subjects: Adamantane - administration & dosage; Adamantane - analogs & derivatives; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Dipeptides - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dose-Response Relationship, Drug; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glipizide; Glipizide - administration & dosage; Humans; Hypoglycemia; Hypoglycemia - blood; Hypoglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Male; Medical sciences; Metformin; Metformin - administration & dosage; Middle Aged; Pharmacology. Drug treatments; Saxagliptin; Type 2 diabetes mellitus; Dipeptidyl-peptidase IV; Endocrinopathy; Type 2 diabetes; Evaluation; Enzyme; Enzyme inhibitor; Metabolic diseases; Glipizide; Type 2 diabetes mellitus; Hypoglycemia; Peptidases; Hypoglycemic agent; Biguanides; Treatment; Sulfonamides; Gliptine derivatives; Sulfonylureas; Hydrolases; Dipeptidyl-peptidase IV inhibitor; Metformin; Comparative study; Saxagliptin
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/03007995.2014.880674

Abstract
Objective:
To compare characteristics of hypoglycemic episodes in patients with type 2 diabetes receiving saxagliptin or glipizide add-on therapy to metformin.
Patients and 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.
Conclusion:
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.