In addition to blood sugar control, may glimepiride have potent antioxidant, anti-inflammatory and angiogenic properties?

Type 2 diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia due to progressive defects in insulin secretion against the background of insulin resistance, which often leads to absolute insulin deficiency, which leads to complex phenomena and is exacerbated by central obesity and increases the risk of
atherosclerosis and related cardiovascular diseases.
Therefore, hypoglycemic therapy, in addition to providing good glycemic control, can help prevent diabetic complications
.
Glimepiride is a second-generation sulfonylurea that stimulates the release of insulin
from β cells of the pancreas.
This drug mainly stimulates insulin secretion, but has been shown to have other extrapancreatic effects
in animal models.

An article published by Saga University in Japan in Cardiovasc Diabetol revealed that glimepiride may have other effects besides blood sugar control in patients with type 2 diabetes.
The purpose of this study was to elucidate the effect of
glimepiride on cardiovascular system-related biomarkers in patients with diabetes.

Research Methods:

Study population: 45 patients who agreed to participate in the study were selected
.
Inclusion criteria included: 1) age> 30 years, 2) type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) > 6.
5%, and 3) being treated with diet, exercise, α-glucosidase inhibitors (α-GIs), and/or first-generation sulfonylureas such as glibenclamide (<5 mg/day) or gliclazide (<80 mg).

。 Exclusion criteria are: 1) serious diabetic complications such as stage > 3A nephropathy or stage >B retinopathy; 2) Liver dysfunction, such as AST>80IU/l or ALT>80IU/l; 3) cancer; 4) renal insufficiency (serum creatinine> 2.
0 mg/dl); 5) Oral treatment
with glimepiride, metformin or pioglitazone.

Study protocol: All patients were treated
with glimepiride upon study entry.
Glimepiride was originally intended as: 1) a new drug for diabetics who received diet/exercise therapy but did not have anti-diabetic medications; 2) the use of α-GIS for additional treatment in patients with poor glycemic control; or 3) exchange for first-generation sulfonylureas such as glibenclamide or gliclazide
in patients with poor glycemic control.
The dose of glimepiride starts with 1 mg per day and increases to 6 mg per day until HbA1c < 6.
5%
in patients receiving new drugs or adjuvant therapy with glimepiride as α-GIs.
If glimeclamide or gliclazide is replaced with glimeride, the initial amount of glimepiride is determined with reference to previous reports, i.
e.
1 mg of glimepiride is equivalent to 1.
5 mg of glibenclamide or 20 mg of gliclazide
.
Adverse events
were recorded continuously.
In all enrolled patients, various blood biomarkers associated with cardiovascular pathophysiology were detected at baseline before starting glimepiride therapy and 24 weeks after starting glimepiride
.

Outcome:

1.
Changes in various blood glucose indicators after administration After starting glimepiride, HbA1c and fasting blood glucose (FPG) levels decreased, and HOMA-β values increased
significantly.
Plasma insulin levels and HOMA-R values were comparable before and after treatment
.
After 24 weeks, HbA1c < 6.
5%
in 23 patients.
At 24 weeks, the average dose of glimepiride was 2.
6 mg, and 13 patients (38%) treated with only 1 mg of glimepiride had HbA1c < 6.
5% (Figure 1).

Six patients (17%) developed mild hypoglycaemia but recovered without intensive assistance, and none developed severe hypoglycaemia
requiring active third-party intervention during the study.

Compared with pre-treatment*p < 0.
05, **p < 0.
01 HbA1c = hemoglobin A1c, HOMA = steady-state model assessment
.

Fig.
1 Changes in fasting blood glucose (a), glycated hemoglobin (b), fasting plasma insulin (c), HOMA-R (d) and HOMA-β (e) levels after glimepiride treatment

2.
Changes in biomarkers after glimepiride administration The levels of hsCRP, PTX3 and most inflammatory cytokines, including IL-1β, IL-6, TNF-α, IFN-γ and MCP-1, did not change after glimepiride treatment
, while BNP levels decreased significantly.
Eotaxin, FGF-2 and toxic AGE levels decreased
significantly after treatment.
In addition, G-CSF and GM-CSF levels showed an upward trend, while VEGF, soluble CD40 ligands, chemokines, MIP-β, and soluble RAGE levels decreased
.

Hollow columns mean "before treatment" and solid columns mean "after treatment"
.
*P < 0.
05 compared to
before treatment.
G-CSF = granulocyte colony-stimulating factor, GM-CSF = granulocyte macrophage colony-stimulating factor, FGF = fibroblast growth factor, VEGF = vascular endothelial growth factor, MIP = macrophage inflammatory protein, glycer-AGE = glyceraldehyde-derived advanced glycosylation end product, sRAGE = soluble receptor of advanced glycosylation end product

Fig.
2 Biomarkers after glimepiride treatment Changes in serum or plasma levels

The results of this study confirm that glimepiride may have angiogenic properties and that the results are not related to lowering blood glucose levels or HbA1c levels, and these results may depend on the uniqueness of the drug itself, unfortunately the study did not assess the effect of treatment on diabetic retinopathy because there were no patients with diabetic retinopathy, but based on this study, in future studies, it can be further explored whether glimepiride can improve or prevent diabetic complications, including macro and micro
。