Introduction to Metformin
Metformin is a widely prescribed oral antidiabetic medication primarily used to manage Type 2 Diabetes Mellitus (T2DM). As part of the biguanide class of drugs, metformin works by decreasing hepatic glucose production, enhancing insulin sensitivity, and increasing peripheral glucose uptake and utilization¹. Its mechanism of action involves the inhibition of gluconeogenesis and fatty acid oxidation in the liver through the activation of AMP-activated protein kinase (AMPK), resulting in lowered glucose levels without causing hypoglycemia¹.
Prevalence and Incidence of Type 2 Diabetes
Type 2 Diabetes Mellitus (T2DM) has become a global health concern, affecting more than 463 million people as of 2019, with projections estimating this number will rise to 700 million by 2045². Common risk factors include obesity, sedentary lifestyle, and genetic predisposition³.
Metformin’s Effectiveness in Various Patient Populations
Metformin is considered a first-line therapy for most patients with T2DM, offering a substantial reduction in HbA1c (by approximately 1.5% to 2%⁴). Patients who are overweight or obese particularly benefit from the drug, as metformin is weight-neutral and may even contribute to weight loss⁶.
Contraindications and Limitations
However, metformin is contraindicated in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m²) due to the risk of lactic acidosis⁸. The drug is also not recommended for individuals with liver disease, severe heart failure, or conditions that predispose them to hypoxia⁹.
Metformin’s Role Beyond Glycemic Control: Cardiovascular Benefits
Recent research has highlighted metformin’s potential role in mitigating atherosclerosis through telomere stabilization. By enhancing the phosphorylation of AMPK and PGC-1α, metformin increases telomerase activity and TERT (telomerase reverse transcriptase) protein levels in vascular smooth muscle cells (VSMCs)⁷. Studies also confirm that the absence of telomerase activity accelerates atherosclerosis and cellular aging, further emphasizing metformin’s protective role⁷.
Key Findings in Animal Models
In the ApoE knockout (KO) mouse model, metformin has been shown to reduce the progression of atherosclerotic plaques, improving plaque stability. Although it did not reduce overall plaque size, it significantly decreased markers of inflammation and enhanced cardiovascular health⁷.
Detailed Lipid Profile Improvements
Metformin’s effects on lipid levels in high-fat diet (HFD)-fed ApoE KO mice were substantial:
- Total cholesterol decreased from 485.1 ± 43.2 mg/dl to 358.6 ± 12.2 mg/dl.
- Triglycerides reduced from 103.9 ± 14.2 mg/dl to 59.4 ± 3.7 mg/dl.
- LDL cholesterol dropped from 304.2 ± 30.4 mg/dl to 235.9 ± 10.9 mg/dl⁷.
Additionally, whole-body fat mass was reduced from 485.1 ± 43.2 mg/dl to 358.6 ± 12.2 mg/dl⁷.
Anti-inflammatory Effects
Metformin also lowered plasma C-reactive protein (CRP) levels, indicating reduced inflammation and a decreased cardiovascular risk⁷.
Conclusions and Key Takeaways
- Metformin remains a cornerstone treatment for managing Type 2 Diabetes Mellitus⁶, especially in patients who are overweight or obese.
- Beyond glycemic control, metformin offers cardiovascular benefits, including reduced atherosclerosis progression and enhanced lipid profiles, supported by both in vitro and in vivo studies⁷.
- Patients with renal impairment and certain other conditions should avoid metformin due to the risk of lactic acidosis.
These findings underscore metformin’s potential not only as a diabetes treatment but also as a therapeutic agent in reducing cardiovascular risks through mechanisms like telomere stabilization and anti-inflammatory effects.
