Volume 20, Issue 6P2 p. 76S-86S

Effect of Multiple-Dose Gatifloxacin or Ciprofloxacin on Glucose Homeostasis and Insulin Production in Patients with Noninsulin-Dependent Diabetes Mellitus Maintained with Diet and Exercise

Dr. Diptee A. Gajjar B. Pharm., Ph.D.

Corresponding Author

Dr. Diptee A. Gajjar B. Pharm., Ph.D.

Departments of Clinical Pharmacology/Experimental Medicine, Bristol-Myers Squibb Pharmaceutical Research Institutes, Princeton, New Jersey.

Department of Clinical Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institutes, Route 206 and Provinceline Road, Princeton, NJ 18543-4000, USA.Search for more papers by this author
Dr. Frank P. LaCreta Ph.D.

Dr. Frank P. LaCreta Ph.D.

Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institutes, Princeton, New Jersey

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Dr. Georgia D. Kollia Ph.D.

Dr. Georgia D. Kollia Ph.D.

Biostatistics and Data Management, Bristol-Myers Squibb Pharmaceutical Research Institutes, Princeton, New Jersey

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Dr. Randall R. Stolz M.D.

Dr. Randall R. Stolz M.D.

GFI Pharmaceutical Services, Inc., Evansville, Indiana.

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Dr. Sheldon Berger M.D.

Dr. Sheldon Berger M.D.

Chicago Center for Clinical Research, Chicago, Illinois.

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Dr. William B. Smith M.D.

Dr. William B. Smith M.D.

New Orleans Center for Clinical Research, New Orleans, Louisiana.

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Ms. Mary Swingle R.N.

Ms. Mary Swingle R.N.

Departments of Clinical Pharmacology/Experimental Medicine, Bristol-Myers Squibb Pharmaceutical Research Institutes, Princeton, New Jersey.

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Dr. Dennis M. Grasela Pharm.D., Ph.D.

Dr. Dennis M. Grasela Pharm.D., Ph.D.

Departments of Clinical Pharmacology/Experimental Medicine, Bristol-Myers Squibb Pharmaceutical Research Institutes, Princeton, New Jersey.

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First published: 17 January 2012
Citations: 51

Abstract

Study Objectives. To compare the effects of gatifloxacin and ciprofloxacin on glucose homeostasis, including glucose tolerance test (GTT), pancreatic β-cell function, and insulin production and secretion in patients with noninsulin-dependent (type 2) diabetes mellitus (NIDDM) maintained with diet and exercise; and to evaluate the pharmacokinetics, safety, and tolerability of gatifloxacin.

Design. Randomized, double-blind, placebo-controlled, multiple-dose study.

Setting. GFI Pharmaceutical Services, Inc., Evansville, Indiana; Chicago Center for Clinical Research, Chicago, Illinois; and New Orleans Center for Clinical Research, New Orleans, Louisiana, USA.

Patients. Forty-eight men and women with NIDDM.

Interventions. Patients were assigned sequentially at enrollment to receive gatifloxacin 400 mg/day orally, ciprofloxacin 500 mg twice/day orally, or placebo for 10 days. Oral GTTs were performed on specific days throughout the study, as well as measurements of serum glucose, serum insulin, and C-peptide levels. Physical examinations, electrocardiograms, spirometry, and clinical laboratory tests were performed before dosing and on selected dosing days.

Measurements and Main Results. Gatifloxacin had no significant effect on glucose tolerance and pancreatic β-cell function, as shown by oral GTT results and insulin and C-peptide levels. Fasting glucose levels 0–6 hours after gatifloxacin administration on days 1 and 10 showed a downward trend, but it was not significant compared with placebo; results were similar with ciprofloxacin. Gatifloxacin also lacked a long-term effect on fasting insulin levels, but this was not shown for a short-term effect, suggesting a modest, transient effect on insulin release. On the other hand, ciprofloxacin had no short-term effect but produced a more sustained effect on insulin release and production. The pharmacokinetics of gatifloxacin in patients with NIDDM were similar to those in healthy subjects. Overall, subjects tolerated treatment well. All reported drug-related adverse events were mild to moderate in intensity. The frequency of adverse events was similar in gatifloxacin- and ciprofloxacin-treated patients, and only slightly higher than in placebo-treated patients.

Conclusion. Gatifloxacin was well tolerated in patients with NIDDM controlled by diet and exercise. It had no significant effect on glucose homeostasis, β-cell function, or long-term fasting serum glucose levels, but it did cause a brief increase in serum insulin levels.