Insulinotropic Potential of Moxifloxacin and Gemifloxacin: An In Vivo Rabbits Model Study Followed by Randomized Phase I Clinical Trial

Abstract

Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic patients. However, diabetic patients are usually on polypharmacy, so we cannot attribute the dysglycemia specifically to FQs. To answer the question as to whether Moxifloxacin and Gemifloxacin influence blood glucose levels and serum insulin levels or otherwise, rabbits were used as experimental animals in an in vivo model followed by a phase I randomized clinical trial in euglycemic healthy volunteers. The effects on the serum insulin and blood glucose levels in the Moxifloxacin and Gemifloxacin treated groups were, respectively, determined on the fifth day in both the in-vivo rabbits model and in the test subjects of the phase I clinical trial. The effects of these drugs were also checked on the histomorphology of the pancreas in the rabbits. The findings of our study suggest that Moxifloxacin and Gemifloxacin significantly (p < 0.05) reduced the blood glucose levels via a subsequent significant shift in the serum insulin levels both in the in vivo animal model and in the test subjects of the phase I clinical trial. No prominent effects on the beta cells histomorphology were noted in this study. Moxifloxacin showed a more significant effect than Gemifloxacin. The insulinotropic effect was comparable to the effect of Glibenclamide. It is concluded that Moxifloxacin and Gemifloxacin have a significant blood glucose lowering effect mediated through insulinotropic action. (Clinical Trials.gov identifier: NCT04692623).

The Effects of Moxifloxacin and Gemifloxacin on the ECG Morphology in Healthy Volunteers: A Phase 1 Randomized Clinical Trial

“…However, overall, no substantial QT prolongation was seen in our research investigations with gemifloxacin as compared to moxifloxacin. The same weak effect was reported for gemifloxacin as compared to moxifloxacin in our previous study on potassium channels in pancreatic beta cells [ 41 ]. The results of our study compared well with the effects of moxifloxacin reported previously, where a retrospective analysis of pooled data from QT studies with moxifloxacin as a single 400 mg dose in healthy volunteers was studied [ 42 ].…”

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“…The precise mechanism of sitafloxacin-induced dysglycemia is not fully understood; it might be fluoroquinolones'direct effect of the on glucose metabolism or the result of the combined action of multiple factors [7]. Animal studies show that the mechanism of fluoroquinolone induced hypoglycemia is to promote insulin secretion by blocking ATP sensitive potassium channels in pancreatic beta cells [8,9]. According to clinical research, levofloxacin and ciprofloxacin may contribute to aberrant blood glucose levels by impairing cells' GLUT1 and glucose transport mechanisms [10].…”

The Research Status, Potential Hazards and Toxicological Mechanisms of Fluoroquinolone Antibiotics in the Environment

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