Better glucose utilization improves carbohydrate metabolism
Activates key pathways in the body that regulate glucose and fat metabolism in the liver
Metformin is in the class of medications called biguanides. Metformin helps control the amount of glucose in the blood and the amount released by the liver. It is used along with lifestyle modifications to lower blood sugar in people diagnosed with type 2 diabetes. It is considered a first-line treatment because it is effective, safe, and low-cost.
Metformin also facilitates weight loss. Proposed mechanisms of action for metformin’s weight loss effect include:
Leucine, metformin, and sildenafil synergistically work to reduce weight and triglycerides by activating SIRT1, according to a phase 2 clinical trial. Weight loss during the 16-week study period was linear, which suggests it will continue at the same rate. Activating Sirt1 is expected to support weight loss, improve cardiovascular function, and improve lipid metabolism.
Methylcobalamin or cyanocobalamin is a human-made form of vitamin B12. Vitamin B12 is a water-soluble vitamin naturally found in some foods and added to others. B12 supplements are available in both oral and injectable forms. B12 deficiency is fairly common, affecting 6% of people under age 60 and nearly 20% of those over age 60. Restoring B12 levels can help with weight-loss efforts.
Metformin is used to decrease blood glucose and fat deposition in the liver and to treat type 2 diabetes. Metformin decreases glucose production in the liver, decreases glucose absorption from the intestines, and improves insulin sensitivity. Metformin lowers blood glucose by about 25% to 30%, with a low risk for hypoglycemia. Metformin also improves the body’s response to insulin, a hormone that shuttles glucose from the bloodstream into cells.
Researchers found that combining leucine, metformin and sildenafil worked better than metformin alone at activating the 5′ adenosine monophosphate-activated protein kinase (AMPK)/Sirtuin 1 (Sirt1) pathway, which regulates glucose and fat metabolism in the liver.
The combination also increases liver energy metabolism and decreases inflammation. Leucine is a direct Sirt 1 activator. Sildenafil inhibits phosphodiesterase 5 which increases nitric acid and increases blood flow. This pathway also interacts with the Sirtuin pathway, as it stimulates Sirt 1.
Obesity, insulin resistance, dyslipidemia, and cardiovascular disease have all been linked to low B12 levels. B12 is involved in the regulation of DNA coding for proteins (epigenetics) as well as many metabolic processes in the cell. There is mounting evidence that B12-DNA interactions regulate lipid metabolism and play a role in fat deposition.
The weight-loss potential for metformin has long been recognized and has been leveraged to treat type 2 diabetes. More recent clinical trials have demonstrated that sildenafil and leucine potentiate metformin’s weight loss potential. Together these medications work together on glucose metabolism through the AMPK/Sirt 1 pathways, important pathways involved in glucose and fat metabolism.
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Metformin has been used for decades to manage blood sugar in type 2 diabetes. Metformin decreases the amount of glucose absorbed through your intestines and the amount produced in your liver. Metformin also improves your body’s sensitivity to insulin, making it easier for cells to transport glucose from the blood into cells where it can be used for energy.
The most serious potential side-effect of metformin is lactic acidosis. Lactic acidosis can be life-threatening, so it is important to let your healthcare provider know if you have a history of kidney disease. Other risk factors for lactic acidosis include being over age 65 or having a history of:
Some medications can also increase your risk of metabolic acidosis, so it’s important to tell your healthcare provider about every medication you are taking.
Metabolic acidosis is a serious potential side-effect of metformin that may occur in some high-risk patients. Symptoms associated with lactic acidosis include:
Let your healthcare provider and pharmacist know if you are taking any medications (over-the-counter or prescriptions) to ensure that any medications you are taking do not interact with metformin. Prescription medications that have the potential to increase lactic acid are a concern, including some anticancer, antimicrobial, and HIV medications.
Excess alcohol consumption is a risk factor for lactic acidosis, the most serious (though uncommon) potential side-effect of taking metformin. If you drink alcohol in excess, generally defined as more than one drink per day for women or two drinks per day for men, let your healthcare provider know.
Researchers found that combining leucine, sildenafil, and metformin worked better than metformin alone at activating the SIRT 1 pathway. The SIRT 1 pathway is a key pathway that regulates glucose and fat metabolism in the liver. Leucine directly stimulates the SIRT1 pathway, and sildenafil increases nitric oxide, which increases blood flow.
Weight loss from metformin alone is a gradual process. The average weight loss is 5 to 6 pounds. This is why metformin is combined with leucine, vitamin B12, and sildenafil. It is also important to consume a healthy diet and engage in physical activity. Metformin synergy supports your weight loss efforts.
Yes, metformin can cause nausea and upset stomach. However, for most people, these symptoms improve within two weeks. It is important to let your healthcare provider know about any symptoms you may be experiencing.
Yes, sildenafil (Viagra, Revatio) is used to treat erectile dysfunction. Sildenafil is a type of phosphodiesterase inhibitor. By inhibiting the breakdown of phosphodiesterase, nitric acid is active longer. Nitric oxide relaxes smooth muscle and dilates blood vessels which increases blood flow. In addition, sildenafil was found to help metformin activate the SIRT 1 pathway.