Metformin hydrochloride
[CAS# 1115-70-4]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Pancreatic hormones and other blood sugar regulating drugs
• Name: Metformin hydrochloride
• Synonyms: 1,1-Dimethylbiguanide hydrochloride
• Molecular Formula: C₄H₁₁N₅.HCl
• Molecular Weight: 165.62
• CAS Registry Number: 1115-70-4 (15537-72-1)
• EC Number: 214-230-6
• SMILES: CN(C)C(=N)N=C(N)N.Cl

Properties

• Solubility: 50mg/mL (DMSO)
• Melting point: 223-226 °C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335-H412
• Safety Statements: P261-P264-P270-P271-P273-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P312-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Reproductive toxicity	Lact.	-	H362
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	2	H312
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H412

Discovery and Applications

Metformin hydrochloride is a widely used oral medication primarily prescribed for the treatment of type 2 diabetes mellitus. It is known for its effectiveness in controlling blood glucose levels and its role in managing insulin resistance. The discovery and development of metformin marked a significant advancement in diabetes care, offering a safer and more effective treatment option compared to earlier drugs.

The roots of metformin’s discovery can be traced back to the use of a plant called *Galega officinalis* (goat's rue or French lilac), which had been traditionally used in folk medicine for centuries. In the early 20th century, researchers identified a compound called guanidine in this plant, which had blood sugar-lowering properties. However, guanidine itself was found to be too toxic for therapeutic use. This led to the synthesis and testing of related compounds, one of which was metformin, first described in the scientific literature in the 1920s.

Metformin was initially overshadowed by the introduction of insulin and other antidiabetic agents, and it wasn't until the 1950s that its potential was recognized. The French physician Jean Sterne conducted clinical trials that demonstrated metformin’s ability to lower blood sugar without causing severe side effects. Following these successful trials, metformin was introduced in Europe in the 1950s and later in the United States in 1995.

Metformin hydrochloride works by reducing the amount of glucose produced by the liver, increasing the sensitivity of muscle cells to insulin, and slowing the absorption of glucose from the intestines. Unlike some other antidiabetic medications, metformin does not cause significant weight gain or hypoglycemia, making it a preferred first-line treatment for type 2 diabetes. Its efficacy in reducing HbA1c levels, a marker of long-term blood glucose control, has been well-documented, contributing to its widespread use.

Beyond its primary role in diabetes management, metformin hydrochloride has also been explored for its potential benefits in other areas of health. Studies have suggested that metformin may have a protective effect against cardiovascular diseases, which are a common complication of diabetes. Additionally, there is growing interest in its possible role in cancer prevention, particularly for certain types of cancer such as breast and colorectal cancer, although more research is needed to confirm these effects.

Another area of active research is the potential use of metformin in delaying the onset of type 2 diabetes in individuals with prediabetes. Clinical trials have shown that metformin can significantly reduce the risk of developing diabetes in high-risk individuals, which has led to its consideration as a preventive treatment in certain populations.

Metformin’s relatively low cost, safety profile, and effectiveness have made it one of the most prescribed medications worldwide. It is typically taken in tablet form, with immediate-release and extended-release versions available to suit different patient needs. Despite its widespread use, metformin is not without side effects. The most common side effects include gastrointestinal issues such as nausea, diarrhea, and abdominal discomfort. Rarely, metformin can cause a serious condition called lactic acidosis, particularly in individuals with kidney or liver impairment, which is why proper patient selection and monitoring are essential.

In recent years, metformin has also been studied in the context of aging and longevity. Some research suggests that metformin may have anti-aging properties and could potentially extend lifespan by mimicking some of the effects of calorie restriction, a known intervention for increasing lifespan in various organisms. This has led to ongoing studies to evaluate metformin’s potential as a geroprotective drug, although it is not currently approved for this purpose.

In summary, metformin hydrochloride is a cornerstone in the treatment of type 2 diabetes, with a history rooted in traditional medicine and decades of clinical research. Its applications continue to expand beyond diabetes, highlighting its potential as a multifaceted therapeutic agent.

References

2024. Formulation Optimization of Metformin-Loaded Propyl Moringa Gum Beads. Journal of Pharmaceutical Innovation.
DOI: 10.1007/s12247-024-09897-9

1998. Efficacy and Metabolic Effects of Metformin and Troglitazone in Type II Diabetes Mellitus. The New England Journal of Medicine.
DOI: 10.1056/nejm199803263381303

1998. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. European Journal of Endocrinology.
DOI: 10.1530/eje.0.1380269