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.

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 (HbA_1c) >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 HbA_1c. 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:

ClinicalTrials.gov identifier: NCT00575588.

Keywords::

• Glipizide
• Hypoglycemia
• Metformin
• Saxagliptin
• Type 2 diabetes mellitus

Transparency

Declaration of funding

This research was supported by Bristol-Myers Squibb and AstraZeneca LP.

Declaration of financial/other relationships

M.L.M. has served as a speaker for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, and Takeda, and as a consultant for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Sunovion, and Teva. G.M. is an employee of AstraZeneca LP.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank Mark Donovan PhD of Bristol-Myers Squibb for statistical assistance and critical review of the manuscript. Medical writing support for the preparation of this manuscript was provided by Stephanie Leinbach PhD and Janet E. Matsuura PhD from Complete Healthcare Communications, Inc. (Chadds Ford, PA, USA), with funding from Bristol-Myers Squibb and AstraZeneca LP.