Hypoglycaemic and Antidiabetic Sulphonamides

Young, F. G.

doi:10.1136/bmj.2.4990.431

Cited by 12 publications

(1 citation statement)

References 6 publications

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“…The hypoglycaemic potential of SU compounds was first recognised in 1942 based on observations that patients prescribed a sulphonamide antibiotic (para-amino-benzene-sulfamido-isopropylthiodiaz ol, 2254 RP), while treating Salmonella typhi infection, developed very low blood glucose [19]. Four years later it was reported that this group of antibiotic compounds, now known as SU, stimulate insulin release from beta-cells [20]. Since then, three generations of SU class drugs have been developed and prescribed worldwide to hundreds of millions of patients with T2D [21].…”

Section: Discussionmentioning

confidence: 99%

OZ101, an oligofructose prebiotic, may prolong sulphonylurea efficcy in patients with type 2 diabetes: a pilot study: OZ101 and sulphonylurea-mediated glycaemic control

Gorgani¹

2022

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Aims: The sulphonylurea class of anti-diabetes drugs lose efficacy over time due to progressive beta-cell failure. Their long-term use may exacerbate gut microbial dysbiosis as they are derivatives of sulphonamide antibiotics. We conducted a pilot study to test the hypothesis that OZ101, administered as adjunctive prebiotic therapy, improves beta-cell function and glycaemic control in sulphonylurea-treated patients.Materials and Methods: Subjects with type 2 diabetes on sulphonylurea monotherapy (n=30) were randomized in a 24-week parallel dose range-finding study to either continue receiving their usual sulphonylurea-only treatment or add a thrice-daily regimen of 13.5 or 27 g/d doses of OZ101. HOMA-B, glycaemic parameters after 12 hours fasting, and glucose area under the curve (AUC; over 240 minutes) after intake of a pre-defined calorie milkshake were collected at baseline and 24 weeks.Results: Over 24-weeks, control subjects on sulphonylurea-only showed a decline in beta-cell function (35.54% decrease in HOMA-B from baseline, p = 0.01), whereas subjects taking sulphonylurea+13.5 g/d OZ101 improved (22.9% increase in HOMA-B from baseline, p = 0.031). There was a 0.95% (10mmol/mol) difference in HbA1c (p = 0.047) and 607 mmol/l*240min AUC (p = 0.039) in favour of the sulphonylurea +13.5g/d OZ101 compared with control group. HbA1c and AUC were not altered in subjects treated with sulphonylurea+27 g/d OZ101 compared with the control group. Microbiome profiling suggested reciprocal relationships in beneficial versus detrimental bacteria between control and treatment groups.Conclusions: Adjunctive intake of 13.5g/d OZ101 in patients on sulphonylurea therapy was safe, well-tolerated and associated with improved beta-cell function and stabilization of glycaemic control over 24 weeks. Absence of similar response for the 27 g/d OZ101 group may relate to changes in gut microbiome profiles. Future studies will determine the mechanistic link between OZ101 therapy, changes in gut microbiome, and metabolic responses.

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Section: Discussionmentioning

confidence: 99%