Metformin synergy is a combination of three medications/nutrients that work together to activate Sirt1, an enzyme that regulates energy and fat metabolism, as well as B12, a vitamin that increases energy, reduces fatigue, and jump-starts a sluggish metabolism.

Metformin is used to treat type 2 diabetes because it lowers the amount of sugar in the blood and keeps fat from building up in the liver.

Researchers found that taking leucine, metformin, and sildenafil together worked better than metformin alone to stimulate the 5′ adenosine monophosphate-activated protein kinase (AMPK)/Sirtuin 1 (Sirt1) pathway. This pathway controls how the liver breaks down glucose and fat. In addition, the combo boosts hepatic energy metabolism and reduces inflammation. Sirt1 is activated directly by leucine. Sildenafil inhibits phosphodiesterase 5, increasing nitric acid and blood flow. As Sirt1 is stimulated, this route interacts with the Sirtuin pathway.

Potential side effects from metformin synergy include:

Rare Metformin Synergy side effects:

Metformin is recommended as the first treatment for type 2 diabetes by the American Diabetes Association (ADA). This is because it has been studied for many years and is inexpensive. But sometimes, metformin alone is not enough.

Jardiance is not the only metformin-related medication on the market, but it is one of the few that also reduces the risk of heart and kidney problems while regulating blood sugar. Synjardy is a combination of metformin and Jardiance in a single pill.

Certain drugs might increase the chance of getting lactic acidosis when using metformin. You should inform your doctor if you are using any of the following medications:

Certain medications can also make it harder to metabolize and remove metformin from your body. Tell your doctor if you've been taking any of the following medicines before taking metformin:

Avoid drinking excessive amounts of alcohol when taking metformin. When you take metformin and drink alcohol at the same time, your chances of getting low blood sugar or lactic acidosis go up.

Metformin and sildenafil can be taken together. In fact, in one study, men who had erectile dysfunction and insulin resistance had much better erectile function once they started taking sildenafil and metformin together. Insulin resistance and diabetes can interfere with nitric oxide production in the lining of blood vessels. Sildenafil is a phosphodiesterase-5 inhibitor that prolongs the activity of nitric oxide and increases blood flow into the penis.

http://dx.doi.org/10.18535/jmscr/v7i1.06

No adverse drug interactions have been found between metformin and Viagra. Instead, researchers have found that combining metformin with a phosphodiesterase-5 inhibitor like Viagra can improve erectile function in men with diabetes.

Sulfonylureas have been around since the 1950s. They are typically used as second-line therapy following metformin since they are effective, can reduce A1C by 1-2%, and are affordable in generic form. They function by binding to adenosine triphosphate (ATP)-dependent potassium channels in pancreatic cells, resulting in insulin secretion.

https://diabetesjournals.org/clinical/article/30/2/72/31558/Management-of-Type-2-Diabetes-What-Is-the-Next

Sildenafil is a phosphodiesterase-5 inhibitor. It prolongs the activity of nitric oxide, dilating blood vessels and increasing blood flow. Sildenafil is used to treat erectile dysfunction. There is no evidence that sildenafil treatment causes any changes in metabolism or can cause weight loss.

A recent animal study indicated that sildenafil might even contribute to weight gain. The researchers recommended further research to better understand the relationship between sildenafil and metabolism.

https://www.nature.com/articles/s41387-018-0026-0

Metformin is an excellent first-line treatment for diabetes. However, if you still have signs of elevated blood sugar, this may be a sign that metformin is not working for you. Signs of persistently high blood sugar include:

Metformin can improve erectile function if insulin resistance and high blood sugar are contributing factors to erectile dysfunction (ED). Metformin can improve the activity of nitric oxide, which increases blood flow into the penis. Metformin also modulates the activity of the sympathetic nervous system. The sympathetic nervous system causes blood vessels to constrict, decreasing blood flow into the penis. By reducing sympathetic tone and increasing nitric oxide, metformin can help improve erectile function.

https://tau.amegroups.com/article/view/14362/15465

Metformin is a long-term treatment. Most people who start taking metformin continue it for the rest of their lives. If you have type 2 diabetes and obesity and lose a significant amount of weight, your blood sugar levels may return to normal.

When researchers studied metformin's activity, they found that it was able to reduce blood sugar after meals by 25% to 90%. Metformin typically starts working within the first week of use, and it takes about 2 months before it has its full effect.

https://diabetesjournals.org/care/article/29/4/759/39300/Efficacy-Tolerability-and-Safety-of-a-Novel-Once

Do not take sildenafil if you are allergic to any of its components or are taking any of the following medications:

Metformin reaches a maximum concentration in your bloodstream about 2.5 hours after you take it. About 50–60% of the dose is metabolized and active, and the rest is not absorbed from the intestines.

Once you start taking metformin regularly, it reaches a steady state in your bloodstream after about 24 to 48 hours. Food slightly reduces absorption.

Metformin is excreted by the kidneys. About half of the dose is eliminated in about 6.2 hours.

https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=281e6da6-21e0-61eb-e054-00144ff8d46c&type=display

Metformin can cause stomach upset. If you take metformin once a day, take it with your evening meal. If you take twice daily metformin, take it with your morning and evening meals. Swallow your metformin tablets whole with a full glass of water. Do not chew metformin tablets.

Metformin is typically prescribed for people with type 2 diabetes. But it is also given to people who don't have diabetes to help them lose weight and make their bodies more sensitive to insulin. When combined with a healthy diet, people taking metformin have lost five to 12 pounds over 3 years in one study and over 5% of their body weight over a 15-year period in another study.

https://www.nejm.org/doi/full/10.1056/NEJMoa012512

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829283/

About one-fourth of people taking metformin develop a vitamin B12 deficiency. Symptoms of vitamin B12 deficiency include:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867725/

Metformin can induce weight loss and help improve insulin sensitivity. This combination may help reduce belly fat. Metformin is also reported to reduce appetite levels, which can make it easier for you to follow a low-calorie diet.

Metformin side effects include:

Metformin is not known to harm the kidneys. Metformin is metabolized and excreted from the body in the urine. If you have kidney problems, be sure to let your healthcare provider know. If your kidneys don’t work effectively, you could develop a buildup of lactic acid in your body. This is a rare but potentially fatal side effect.

People with the following conditions or who meet the following criteria should not take metformin:

So that their blood sugar doesn't rise unexpectedly, people with diabetes should either avoid fruits with a high glycemic index (GI) or eat them in small amounts.

Pineapple, watermelon, mango, lychee, and banana have high GI values, making them the worst fruits for diabetics.

After talking to a nutritionist, you could add these fruits to your daily diet along with foods that help keep your blood sugar stable. As an alternative, you can eat low-GI foods like avocado, citrus fruits, berries, papaya, and apples.

Metformin can help with weight loss, especially if you have insulin resistance. Researchers found that the average weight loss is about 5 to 10 pounds. Metformin increases metabolic rate and reduces insulin resistance.

In one study, participants took 2,500 mg of metformin per day. They lost an average of 10 to 14 pounds, which was between 5.6% and 6.5% of their body weight.

Effectiveness of metformin on weight loss in non-diabetic individuals with obesity - PubMed (nih.gov)

Metformin has a positive effect on lipid metabolism. It lowers blood triglycerides and increases HDL (good) cholesterol. Metformin also increases glucose sensitivity for more efficient carbohydrate metabolism. Metformin causes weight loss by decreasing appetite and increasing fat metabolism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291441/

Yes, metformin can modulate your appetite. People who were given metformin ate less food and reported feeling less hungry than those who were not. The researchers concluded that metformin decreases caloric intake in a dose-dependent manner, which leads to a reduction in body weight.

https://pubmed.ncbi.nlm.nih.gov/9526970/

Metformin increases energy production in your body by activating the respiratory chain in the mitochondria. The mitochondria are organelles inside your body cells that produce energy. Metformin increases their ability to produce energy.

Metformin also acts on the liver. It decreases the conversion of other nutrients into glucose and increases your body’s sensitivity to insulin.

Cellular and molecular mechanisms of metformin: an overview - PMC (nih.gov)

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by increased insulin resistance. Metformin may reduce insulin resistance, help with weight management, and reduce the effects of excess androgens. Researchers conclude that more research is needed to determine whether metformin may improve long-term health for women with PCOS, including reducing their risk for diabetes, cardiovascular disease, and endometrial cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200666/

Metformin does not interact with foods, so there are no restrictions on your diet if you are taking it. However, it does interact with alcohol.

Alcohol impairs your liver’s ability to store and release blood sugar. If you drink alcohol on an empty stomach, it can cause low blood sugar, but this effect is more common in people who take insulin.

Metformin-associated lactic acidosis (MALA) is a rare but potentially life-threatening condition. This rare condition may occur more commonly in people who consume excessive alcohol.

https://pubmed.ncbi.nlm.nih.gov/26773926/

Metformin synergy combines leucine, metformin, and sildenafil to activate SIRT 1 in the body. Activating SIRT-1 is expected to support weight loss, improve cardiovascular function, and improve lipid metabolism.

Sildenafil is a phosphodiesterase-5 inhibitor that increases blood flow and dilates blood vessels. Leucine is an essential amino acid and one of the three branched-chain amino acids. Metformin is used to improve insulin resistance and lower blood sugar in people with type 2 diabetes.

Metformin-associated lactic acidosis (MALA) is a rare condition that happens in less than 5 people per 100,000 patient-years of metformin use.

Symptoms of lactic acidosis include:

https://pubmed.ncbi.nlm.nih.gov/26773926/

Metformin can induce weight loss, but it will not occur quickly. On average, most people taking metformin lose about 5 to 7 pounds over a year. However, researchers found that weight loss persisted and continued as long as the participants stayed on metformin.

Combining metformin use with a healthy diet and exercise program can increase weight loss.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308305/

Yes, people without diabetes can take metformin. It is prescribed off-label for weight management in people with type 2 diabetes. It is also prescribed for people without diabetes, though it is not FDA-approved for this purpose. If your doctor believes that the benefits of metformin outweigh the potential side effects, they may prescribe it for you.

https://link.springer.com/article/10.1007/s00228-018-2593-3?shared-article-renderer

According to a 2018 review of multiple studies in the literature that enrolled 8,461 participants, metformin use in people without diabetes led to weight loss. Adolescents lost the most weight when taking 2,000 mg per day. Adults lost weight when taking 3,000 mg per day and 1,000 mg per day.

https://link.springer.com/article/10.1007/s00228-018-2593-3?shared-article-renderer

Metformin can help you lose belly fat. In a 2017 study, metformin was found to reduce body fat, improve body composition, and reduce visceral fat.

Participants took 1,500 mg of metformin per day. The researchers commented that metformin treatment led to a significant reduction in visceral fat in the animal study arm of the experiment. Visceral fat (belly fat) is metabolically active fat. More research is needed to see the long-term effect of metformin on belly fat.

https://doi.org/10.1371%2Fjournal.pone.0171293

Sildenafil can cause low blood pressure. Watch for these signs:

Other common side effects include the following:

Sildenafil can also cause more serious side effects, such as:

In a clinical trial, men with erectile dysfunction and probably cardiovascular disease exercised at their maximal level one hour after taking sildenafil. Exercise testing was well tolerated. Sildenafil had no effect on symptoms, exercise duration, or the presence or extent of heart-related symptoms.

Sildenafil can cause a drop in blood pressure; watch for dizziness and lightheadedness, especially right after exercising.

https://jamanetwork.com/journals/jama/fullarticle/194635

Viagra is a phosphodiesterase-5 inhibitor that increases nitric oxide levels in blood vessels. This dilates blood vessels and increases blood flow. Theoretically, this should allow for increased blood flow to the heart and lungs. Further research is needed.

A 2013 study in the journal Clinical and Translational Science suggested that sildenafil could increase muscle protein synthesis and reduce muscle fatigue. More research is needed to see if Viagra gives athletes an advantage.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076819/

In a study that looked at sildenafil metabolism after drinking energy drinks, researchers found that caffeine could possibly speed up sildenafil metabolism by increasing blood flow to the liver, but the effect was small.

Another study evaluated caffeine intake and ED. Researchers found that drinking one or two cups of coffee per day could reduce your risk of ED, but not any more or less than that.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412629/

https://biomedpharmajournal.org/vol11no3/influence-of-energy-drinks-on-pharmacokinetic-parameters-of-sildenafil-in-rats/

So far, research does not support Viagra as a weight loss treatment.

Viagra is a phosphodiesterase-5 inhibitor, an enzyme that breaks down cGMP. Inhibiting PDE-5 should increase cGMP levels, which should reduce body weight. In an animal study, researchers found that sildenafil did not change the mice’s body weight or composition. However, it did cause white fat to look more like metabolically active brown fat, a promising result. Later studies found no change in brown fat but did find a promising metabolic effect that needs more research.

https://www.nature.com/articles/s41387-018-0026-0

It is best to take sildenafil on an empty stomach. A high-fat or rich meal will slow sildenafil absorption. Take sidenafil one hour before anticipated sexual activity and two hours after eating. If you are hungry, have a light snack.

Metformin is prescribed to treat type 2 diabetes. When you have high blood sugar, your kidneys are unable to resorb all the sugar, and some are lost in the urine. To properly dilute the lost sugar, more water is also excreted in the urine. Therefore, you pee a lot. Once your blood sugars are in a healthy range, you should need to go to the bathroom less often.

You may notice an increase in energy when you take metformin, as your body uses insulin more effectively. High blood sugar causes fatigue and hunger. As your body uses energy more efficiently and you lose weight, your energy levels will continue to increase, especially if you make a healthy, nutritious diet and exercise part of your weight management plan.

Eggs are high in protein and can make you feel full. They are full of healthy fats, proteins, vitamins, and minerals, many of which are antioxidants.

If you are trying to manage your weight, make eggs a part of your meal plan. They help you stay full longer and are relatively low in calories.

Peanuts have a low glycemic index. This means that they will not affect your blood sugar much after you eat them. They are also high in nutrients and protein. As long as you are not allergic to them, make peanuts part of your meal plan. However, measure your servings carefully because peanuts are relatively high in calories.

Metformin, as a treatment for weight management or diabetes, can cause a reduction in vitamin B12 and sometimes folic acid. To help compensate for this, Metformin Synergy contains vitamin B12. Metformin also contains leucine and sildenafil; together, these compounds synergistically activate the SIRT-1 pathway to support your weight loss efforts.

Hemoglobin A1C (HbA1c) is a measurement of your average blood glucose over a three-month period. When your blood sugar is high, more of it sticks to hemoglobin, increasing your HbA1c. HbA1c levels of 6.5% or above suggest that a person may have diabetes.

To reduce your HbA1c, choose a diet that follows the Mediterranean style of eating: high in fruits and vegetables, lean proteins, and healthy fats. Avoid processed foods, trans and saturated fats,

If your HbA1c is over 6.5%, this suggests that you have diabetes. To lower your HbA1c, you may need to change your diet, manage your weight, and try to incorporate physical activity into your daily schedule.

Avoid sugary and processed foods. They cause your blood sugar to spike and plummet, leaving you hungry again. Avoid processed foods. They are typically high in calories, low in nutrients, and cause blood sugar spikes as well. Instead, choose a well-balanced diet rich in fruits and vegetables and lean protein sources.

Take metformin for weight loss with your morning and evening meals. This will help you stabilize your blood sugars overnight and reduce the risk of side effects. Metformin Synergy can cause stomach upset; taking it with a meal reduces the risk of this happening. Swallow your pill whole with a glass of water.

Yes, walking can reduce your A1c and help you manage your weight. According to an analysis of clinical studies, walking lowers body mass index, HbA1c, and diastolic blood pressure. As walking becomes easier for you, try to increase your speed and add hills for more resistance and calorie burn.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201471/

A hemoglobin A1c test is unique among diabetes tests in that it can be done at any time of the day. You do not need to fast or change your diet before having the test.

The best exercise for diabetes and weight management is any that you enjoy and will do regularly. Try to set small goals to increase both aerobic and resistance training and make it a regular part of your day. You can incorporate resistance exercise into your schedule by using your body weight as resistance as you do squats, situps, and wall pushups.

Regular physical activity can help you control your blood sugar, manage your weight, prevent or delay the onset of type 2 diabetes, improve blood lipid levels, lower your blood pressure, and reduce your risk of cardiovascular disease.