Biguanides

What exactly are Biguanides?

The name “biguanidine” frequently refers to a class of medications that act as oral antihyperglycemic agents used to treat diabetes mellitus or prediabetes. A number of biguanide compounds are utilized in pharmaceuticals. Here are several examples:

• Metformin is a medication that is commonly used to treat type 2 diabetes.
• Phenformin has been pulled from the market in the majority of nations due to hazardous side effects.
• Buformin has been taken off the market due to its hazardous consequences.

Metformin (biguanides) is an oral glucose-lowering medication used to treat non-insulin-dependent diabetic mellitus (NIDDM). Although phenformin was withdrawn in many countries due to a link with lactic acidosis, metformin does not pose the same risk when used properly. Metformin is currently frequently used as a single agent as well as in combination with a sulfonylurea. Metformin, unlike sulfonylureas, is not attached to plasma proteins, is not metabolized, and is swiftly removed by the kidney.

Biguanides reduce blood glucose levels without stimulating insulin production.

• Primarily due to increased glucose consumption.
• It promotes the consumption of glucose by the gut and muscles.
• The additional lactate produced is primarily absorbed by the liver and serves as a buffer against excessive glucose lowering while not causing clinical hypoglycemia.
• Biguanides also make the body’s cells more willing to absorb glucose already present in the bloodstream, lowering the level of glucose in the plasma.
• It does not result in weight gain.

Biguanides, unlike other hypoglycemic medications such as sulfonylureas and meglitinides, have no effect on insulin output. As a result, they are effective in Type 2 diabetics and, when combined with insulin therapy, in Type 1 diabetics.

The Evolution of Biguanides

It is a colorless solid that dissolves in water to form an extremely basic solution. These liquids gradually hydrolyze to form ammonia and urea.

The blood-glucose-lowering qualities of the herb Galega officinalis (French lilac), which has been used since the Middle Ages to cure polyuria and other ailments, were discovered to be related to galegine, a guanidine derivative found in the plant’s seeds and flowers. The first biguanides were produced from the French lilac, commonly known as goat’s rue (Galega officinalis). Beginning in the 1980s, additional research led to a re-evaluation of metformin’s usage in type 2 diabetes mellitus (T2DM), offering good evidence for its effectiveness and safety and resulting to FDA approval in 1994. French lilac is used in several herbal medicines. To avoid interactions, if you are on Metformin, do not utilize herbal remedies without first consulting your healthcare provider.

What is the Mechanism of action of Biguanides?

Biguanides act by inhibiting the liver’s ability to convert lipids and amino acids into glucose. They also activate an enzyme (AMPK), which aids cells in responding to insulin and absorbing glucose from the blood. Biguanides, such as metformin, help reduce blood sugar levels in people with Type 2 diabetes through a variety of processes. This is how they work:

1. Lowering Liver Glucose generation: One of the principal activities of biguanides is to reduce the liver’s generation of glucose (sugar). The liver can sometimes release too much glucose into the bloodstream in persons with Type 2 diabetes, contributing to increased blood sugar levels. Metformin inhibits the liver’s excessive glucose synthesis, allowing blood sugar levels to return to normal.

2. Improving Insulin Sensitivity: Biguanides, notably metformin, improve muscle cell insulin sensitivity. Insulin is a pancreatic hormone that allows glucose to enter cells and be used for energy. Insulin resistance occurs when the cells do not respond properly to insulin, making it difficult for glucose to enter and be utilised by the cells. Metformin improves sensitivity, allowing glucose to enter cells more efficiently.

3. Lowering Intestinal Glucose Absorption: Metformin can also lower glucose absorption from the intestines into the bloodstream after a meal. This technique helps to reduce post-meal blood sugar rises generally.

4. Promoting Moderate Weight Loss: Metformin may cause some people to lose a little weight. For those with Type 2 diabetes, this effect can be advantageous because decreasing excess weight can enhance insulin sensitivity and lead to better blood sugar control.

5. Improving Lipid Profiles: Metformin may have beneficial effects on lipid (fat) metabolism, such as lowering triglyceride and low-density lipoprotein cholesterol (LDL-C), which might help minimize the risk of cardiovascular problems in Type 2 diabetes patients.

6. Low Risk of Hypoglycemia: When used alone, biguanides have a low risk of causing low blood sugar (hypoglycemia) compared to other diabetic drugs. This makes them a more secure option, particularly for persons who are prone to hypoglycemic episodes.

While biguanides, such as metformin, can be useful in regulating blood sugar levels in Type 2 diabetes, they are rarely used to treat Type 1 diabetes since they do not address the underlying issue of low insulin production. Furthermore, diabetes care is generally complicated, involving additional medications, lifestyle changes (such as food and exercise), and close monitoring of blood sugar levels. A healthcare provider should select the specific diabetes treatment plan based on the individual’s unique needs and medical history.

Biguanide Side Effects and Toxicity

Diarrhea and dyspepsia are the most prevalent adverse effects, occurring in up to 30% of patients. Because lactic acidosis is the most dangerous side effect, metformin is contraindicated in advanced chronic renal disease. Before beginning metformin, the kidney function should be evaluated. Hypoglycemia and other side effects are likely when metformin is used with other medicines (combination therapy). While biguanides, such as metformin, are typically well-tolerated and successful in the treatment of illnesses such as Type 2 diabetes, they can induce negative effects in some people. It’s important to remember that not everyone may have these adverse effects, and many individuals can safely use biguanides. Here are some of the most prevalent negative effects of biguanides:

1. Gastrointestinal Disturbances: Gastrointestinal side effects are among the most common with biguanides, particularly when the medicine is first started. These could include:

• Vomiting
• Diarrhea
• Constipation
• Discomfort in the abdomen
• Appetite loss

These symptoms are frequently managed or reduced by taking the prescription with food, using extended-release formulations, or beginning with a lower dose and gradually increasing it.

2. Metallic Taste: When taking biguanides, some people may have a metallic taste in their tongue. This is usually a minor and transitory side effect.

3. Vitamin B12 Deficiency: Long-term metformin use has been linked to an increased risk of vitamin B12 deficiency. Anemia, neuropathy, and exhaustion are all indications of vitamin B12 insufficiency. Your healthcare professional may recommend regular monitoring of vitamin B12 levels and supplements if necessary.

4. Warnings: Metformin may not be appropriate for people who have certain medical conditions, such as severe kidney impairment or liver illness. Before beginning metformin or any other medicine, it is critical to address any existing medical conditions and medications with a healthcare provider.

5. Monitoring: When using biguanides, regular blood tests and check-ups are required to monitor blood sugar levels, kidney function, and any potential adverse effects.

If you encounter any negative effects while taking a biguanide medicine, it is critical that you talk freely with your healthcare provider. They can assist in determining whether the adverse effect is due to the medicine, adjusting your treatment plan as needed, and exploring alternate medications as needed.

In summary, the benefits of effective blood sugar control often outweigh the risks of drug side effects, and healthcare providers carefully consider the risks and benefits when prescribing diabetes and related conditions therapies. Always follow your healthcare provider’s instructions and report any concerns or side effects as soon as possible.

While biguanides such as metformin are beneficial in managing Type 2 diabetes, diabetes care is often multidimensional and may require other drugs, lifestyle modifications (such as diet and exercise), and frequent blood sugar monitoring.