TY - JOUR

T1 - A randomised, double-blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women

AU - Juhl, Christian R

AU - Burgdorf, Josephine

AU - Knudsen, Cecilie

AU - Lubberding, Anniek F

AU - Veedfald, Simon

AU - Isaksen, Jonas L

AU - Hartmann, Bolette

AU - Frikke-Schmidt, Ruth

AU - Mandrup-Poulsen, Thomas

AU - Holst, Jens J

AU - Kanters, Jørgen K

AU - Torekov, Signe S

N1 - This article is protected by copyright. All rights reserved.

PY - 2023

Y1 - 2023

N2 - AIMS: The voltage-gated potassium channel K v 11.1 is important for repolarising the membrane potential in excitable cells such as myocytes, pancreatic α- and β-cells. Moxifloxacin blocks the K v 11.1 channel and increases the risk of hypoglycaemia in patients with diabetes. We investigated glucose regulation and secretion of glucoregulatory hormones in young people with and without moxifloxacin a drug known to block the K v 11.1 channel. MATERIAL AND METHODS: The effect of moxifloxacin (800 mg/day for four days) or placebo on glucose regulation was assessed in a randomised, double-blind, crossover study of young men and women (age 20-40 years and BMI 18.5-27.5 kg/m 2 ) without chronic disease, using 6-hour oral glucose tolerance tests (OGTT) and continuous glucose monitoring (CGM). RESULTS: Thirty-eight participants completed the study. Moxifloxacin prolonged the QTcF-interval and increased heart rate. Hypoglycaemia was more frequently observed with moxifloxacin, both during the eight days of CGM and during the OGTT. Hypoglycaemia questionnaire scores were higher after intake of moxifloxacin. Moxifloxacin reduced early plasma-glucose response (AUC 0-30min ) by 7% (95%CI: -9% to -4%, p<0.01), and overall insulin response (AUC 0-360min ) decreased by 18% (95%CI: -24% to -11%, p<0.01) and plasma glucagon increased by 17% (95%CI: 4% to 33%, p=0.03). Insulin sensitivity calculated as Matsuda index increased by 11%, and MISI, an index of muscle insulin sensitivity, increased by 34%. CONCLUSIONS: In young men and women, moxifloxacin a drug known to block the K v 11.1 channel increased QT interval, decreased glucose levels, and was associated with increased muscle insulin sensitivity and more frequent episodes of hypoglycaemia. This article is protected by copyright. All rights reserved.

AB - AIMS: The voltage-gated potassium channel K v 11.1 is important for repolarising the membrane potential in excitable cells such as myocytes, pancreatic α- and β-cells. Moxifloxacin blocks the K v 11.1 channel and increases the risk of hypoglycaemia in patients with diabetes. We investigated glucose regulation and secretion of glucoregulatory hormones in young people with and without moxifloxacin a drug known to block the K v 11.1 channel. MATERIAL AND METHODS: The effect of moxifloxacin (800 mg/day for four days) or placebo on glucose regulation was assessed in a randomised, double-blind, crossover study of young men and women (age 20-40 years and BMI 18.5-27.5 kg/m 2 ) without chronic disease, using 6-hour oral glucose tolerance tests (OGTT) and continuous glucose monitoring (CGM). RESULTS: Thirty-eight participants completed the study. Moxifloxacin prolonged the QTcF-interval and increased heart rate. Hypoglycaemia was more frequently observed with moxifloxacin, both during the eight days of CGM and during the OGTT. Hypoglycaemia questionnaire scores were higher after intake of moxifloxacin. Moxifloxacin reduced early plasma-glucose response (AUC 0-30min ) by 7% (95%CI: -9% to -4%, p<0.01), and overall insulin response (AUC 0-360min ) decreased by 18% (95%CI: -24% to -11%, p<0.01) and plasma glucagon increased by 17% (95%CI: 4% to 33%, p=0.03). Insulin sensitivity calculated as Matsuda index increased by 11%, and MISI, an index of muscle insulin sensitivity, increased by 34%. CONCLUSIONS: In young men and women, moxifloxacin a drug known to block the K v 11.1 channel increased QT interval, decreased glucose levels, and was associated with increased muscle insulin sensitivity and more frequent episodes of hypoglycaemia. This article is protected by copyright. All rights reserved.

U2 - 10.1111/dom.14851

DO - 10.1111/dom.14851

M3 - Journal article

C2 - 36054143

VL - 25

SP - 98

EP - 109

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 1

ER -