Metformin − A Proven Helper That Effectively Protects the Heart of Diabetics
Metformin is one of the first-line medications for patients with type 2 diabetes. In addition to lowering blood glucose levels, it also affects other metabolic processes in the human body. Its antitumor, neuroprotective, and especially cardioprotective effects have been extensively studied, which can be advantageously utilized in the diabetic population.
XR form as a way to improve patient compliance
Metformin suppresses hepatic gluconeogenesis and glycogenolysis and increases the absorption and utilization of glucose in peripheral tissues. It does not increase insulin secretion, so hypoglycemia does not occur during its use.
Therapy usually starts with a dose of 500 mg per day, which can gradually be increased up to 2000 mg per day. Metformin is available in immediate-release or extended-release tablet forms (Glucophage XR). The significant advantage of the XR form is primarily the reduction in the occurrence of gastrointestinal side effects (nausea, vomiting, diarrhea) related to smaller fluctuations in the concentration of the active substance in the body. The reduced frequency of drug administration also positively influences patient compliance.
Reduction of cardiovascular complications incidence
Cardiovascular (CV) complications are among the most common causes of death in patients with type 2 diabetes. Up to 70% of diabetics die due to coronary or cerebrovascular diseases. According to randomized controlled trials (primary evidence comes from the UK Prospective Diabetes Study), the use of metformin can reduce the incidence of cardiovascular complications.
Mechanisms of cardiovascular system protection
Impact on lipid metabolism
Administering metformin supports weight reduction. This effect can be utilized not only in diabetics but also in patients with gestational diabetes or polycystic ovary syndrome. In addition to weight loss, there is also a redistribution of body fat. In patients with metabolic syndrome, fat is stored viscerally, but metformin shifts it to the subcutaneous area. A slight improvement can also be observed in the lipid profile, where LDL cholesterol and triglyceride levels decrease, while HDL cholesterol levels increase.
Anti-atherogenic effect
Atherogenesis begins with the binding of monocytes to activated endothelium and their transformation into macrophages after migrating into the vessel wall. Metformin slows the conversion of monocytes to macrophages, thereby preventing inflammatory infiltration of the vessel wall and reducing the production of pro-inflammatory cytokines. Metformin also reduces the expression of endothelial activators, increases the vascular response to vasodilatory stimuli, and improves the regulation of the coagulation cascade. These changes retard atherogenesis and thrombus formation and accelerate thrombolysis. However, the exact mechanism of endothelial function and atherogenesis influence remains under investigation.
Glycation of proteins and formation of AGEs
Chronic hyperglycemia leads to the intensive binding of glucose to proteins, resulting in non-enzymatic glycation of proteins and the subsequent formation of advanced glycation end products (AGEs). The interaction of AGEs with their receptor leads to inflammation development and increased oxidative stress. Complications also develop when the proteins of the vessel wall are modified and AGEs accumulate in neurons. Metformin reacts with the intermediates of chemical reactions occurring during protein glycation, partially preventing the formation of AGEs.
Reduction of blood glucose levels
Strict glucose control has been shown to reduce the risk of cardiovascular events by approximately 15%. Lowering glycated hemoglobin (HbA1c) level also has a protective effect.
Still a promising drug after half a century
Metformin has been globally used for over 50 years. Many studies have examined its properties, effectiveness, and potential indications. During this long period, it has been necessary to update some studies' results or conduct meta-analyses. Confirming the cardioprotective effect of metformin has supported its use as a first-line drug for patients with type 2 diabetes. Dosage individualization based on the patient's needs is possible when using it. Additionally, metformin can safely be combined with other antidiabetic drugs without requiring its discontinuation or significant dose adjustments.
(kali)
Sources:
1. Zilov A. V., Abdelaziz S. I., AlShammary A. et al. Mechanisms of action of metformin with special reference to cardiovascular protection. Diabetes Metab Res Rev 2019; 35 (7): e3173, doi: 10.1002/dmrr.3173.
2. Wang Y. W., He S. J., Feng X. et al. Metformin: a review of its potential indications. Drug Des Devel Ther 2017; 11: 2421−2429, doi: 10.2147/DDDT.S141675.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
