More Uniform Diurnal Blood Glucose Control and a Reduction in Daily Insulin Dosage on Addition of Glibenclamide to Insulin in Type 1 Diabetes Mellitus: Role of Enhanced Insulin Sensitivity

Abstract

Combination therapy with insulin and sulphonylurea has gained acceptance in management of subjects with Type 2 (non-insulin-dependent) diabetes mellitus. However, its role in management of Type 1 (insulin-dependent) diabetes mellitus remains controversial. In this study, the effect of combination therapy with insulin and glibenclamide on metabolic control, daily insulin dosage, and insulin sensitivity was assessed in subjects with Type 1 diabetes mellitus. Ten men with Type 1 diabetes mellitus participated in a randomized, double-blind, crossover, clinical trial with three treatment regimens, namely (1) insulin alone, (2) insulin and placebo, (3) insulin and glibenclamide, each lasting 3 months. Combination therapy induced: (1) reduction in daily insulin dosage; (2) more uniform blood glucose control as reflected by a lower average 24 h blood glucose level, a smaller difference between mean preprandial and 2 h postprandial blood glucose concentrations, decreased 24 h urine glucose excretion, and a decline in number of hypoglycaemic events; (3) improved insulin sensitivity as expressed by more rapid plasma glucose disappearance rate, without a significant alteration in fasting plasma glucagon and 1h postprandial serum C-peptide levels; when compared with treatment with either insulin alone or with insulin and placebo. Therefore, it is apparent that the addition of glibenclamide to insulin reduces daily insulin dosage and renders a greater uniformity to diurnal blood glucose control, most probably secondary to enhancement of insulin sensitivity.

Anti-Hyperglycemic Effects of Refined Fractions from Cyclocarya paliurus Leaves on Streptozotocin-Induced Diabetic Mice

“…C. paliurus is enriched with flavonoids, triterpenoids, and polysaccharides. So far, over 200 compounds have been isolated and identified from C. paliurus [43], including 27 polysaccharides [44], 137 flavonoids [45], and 43 triterpenoids [18,46]. These isolates showed various pharmacological activities including anti-inflammation, anti-oxidation, anti-microbial, anti-cancer, and anti-diabetes activities [47][48][49].…”

“…After 3 days, the mice with fasting blood glucose level between 11-28 mmol/L were considered as diabetic mice. The diabetic mice were then randomly divided into nine groups, including STZ (model), CPE (ethanol extract from C. paliurus leaves), CPW (water extract from C. paliurus leaves), CPF (flavonoids fraction from C. paliurus leaves), CPP (polysaccharide fraction from C. paliurus leaves), CPT (triterpenoids fraction from C. paliurus leaves), CPF + CPP (flavonoids and polysaccharide fractions from C. paliurus leaves), CPC (flavonoids, polysaccharide, and triterpenoids fractions from C. paliurus leaves), and Glibenclamide (INN) used as a positive control [43,[56][57][58]. The mice were orally administrated the same volume of 60% PEG400 solution (control and STZ), 15 mg/kg INN (INN), 2500 mg/kg CPE (CPE), 1500 mg/kg CPW (CPW), 300 mg/kg CPF (CPF), 180 mg/kg CPP (CPP), 650 mg/kg CPT (CPT), 300 mg/kg CPF + 180 mg/kg CPP (CPF + CPP), and 300 mg/kg CPF + 180 mg/kg CPP + 650 mg/kg CPT (CPC), respectively, once a day (Figure 2A).…”

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

“…However extrapancreatic effects, hypothetically increasing the number of cellular insulin receptors, were speculated [86]. Glibenclamide has been the only SU which was investigated in T1D and the studies were all of a small sample size [30][31][32][33][34] with the largest trial including 40 participants [33]. While some positive effects on HbA 1c , in particular in people with preserved insulin secretion, were observed, with a neutral effect on hypoglycemia, research in this field has petered out in the last decades and SUs do not play a role in people with T1D.…”

Contributions to glucagon and pramlintide pharmacokinetics and pharmacodynamics modeling for multi-hormone artificial pancreas systems

“…Used for T2D to prevent its progression (Blonde et al, 2022). Reduces total daily insulin in T1D, might increase insulin sensitivity (McCoy et al, 1995).…”