Weight measuring.

Berberine vs Metformin: Health Benefits and Side Effects

Although they have similar mechanisms of action, there are differences between metformin and berberine. The main difference lies in the fact that metformin is registered as a medication, while berberine is a dietary supplement. To understand them better, let’s take a closer look at both substances.

Berberine vs Metformin: Discovery and Use

Berberine and metformin are both used in managing type 2 diabetes mellitus. They have diverse historical origins and similar pharmacological characteristics.

Metformin was discovered in the 17th century from the french lilac, Galega officinalis. It appeared as a medication that lowers blood sugar and gained FDA approval in 1994. Its efficacy stems from activating AMP-activated protein kinase (AMPK) and reducing macrovascular complications in diabetes.

On the other hand, berberine dates back to Chinese and Ayurvedic medicine since 3000 BC. It is extracted from the plant Berberis vulgaris and used for various ailments, including hepatitis, diarrhea and dysentery. Berberine’s alkaloid composition positions it as a promising agent for metabolic diseases, lipid metabolism, and brain health.

Despite their distinct origins, both compounds share common therapeutic features for treating obesity, cardiovascular issues, and inflammation. 

Metformin vs Berberine: Health Benefits

Both compounds have the similar ability to activate AMPK and regulate glucose and lipid homeostasis. Here is a comparison of their effects on metabolic health, weight loss, and anti-aging benefits.

Metabolic Health

Berberine and metformin exhibit similarities and differences in their mechanisms of action. Berberine enhances insulin sensitivity through stimulation of insulin-like growth factor-1 (IGF-1). Its ability to inhibit adipocyte proliferation further adds to its value in treating metabolic diseases and obesity.

Metformin shares the common mechanism of improving insulin sensitivity and glucose uptake. Its mechanism involves the activation of AMPK, an enzyme that regulates cellular energy balance.

Even though both compounds affect enhancing insulin sensitivity and glucose homeostasis, they differ in their specific actions. While berberine inhibits adipocyte proliferation, metformin’s main influence is on AMPK activation.

Weight Loss

Metformin and berberine both stimulate calorie restriction and weight loss. Shared mechanisms include the enhancement of insulin sensitivity, which increases glucose uptake and makes weight management easier. Both substances target pathways linked to metabolic regulation, which leads to better energy balance.

However, the key difference lies in their specific modes of action. Berberine possesses the unique ability to activate brown adipose tissue and promote thermogenesis. That process contributes to increased calorie expenditure. On the other side, metformin acts as an appetite suppressant, which contributes to reduced calorie intake

Anti-Aging Potential

Both compounds have attracted the attention of researchers for their promising anti-aging benefits. The activation of AMPK leads to improved mitochondrial function and cellular resilience, key factors in the aging process. Both berberine and metformin demonstrate potential for reducing oxidative stress, a major contributor to aging-related cellular damage.

The distinction in their anti-aging processes lies in berberine’s exceptional capacity to activate sirtuins. Sirtuins are longevity enzymes that regulate gene expression, DNA repair, as well as cellular stress response, and inflammation.

In contrast, metformin has the ability to modulate the gut microbiome, which may slow down the aging process.

Berberine vs Metformin Side Effects

In general, in human body berberine and metformin are well-tolerated. However, in certain cases both substances may manifest side effects. At higher doses, berberine may cause gastrointestinal discomfort, with nausea and diarrhea. As it influences lipid metabolism, there is potential for alterations in cholesterol levels.

Metformin is associated with gastrointestinal side effects such as diarrhea and abdominal discomfort, commonly observed during initial use. It has also been linked to vitamin B12 deficiency through prolonged use, which highlights the importance of monitoring nutritional status.


While both compounds are effective in treating metabolic conditions and weight control, research show that berberine exhibits fewer side effects. Before choosing which one to use, we advise you to consult your physician.


Frequently Asked Questions


Can you take berberine and metformin together?

Taking berberine and metformin together warrants careful consideration. Berberine and metformin have the same pathways in enhancing insulin sensitivity and regulating glucose metabolism. However, combining these compounds may potentiate their individual effects and lead to hypoglycemia.

The combination of berberine and metformin with other medications may reduce their effectiveness or result in adverse effects. Therefore, it is important to use both berberine and metformin under the supervision of a physician.


How to use berberine for weight loss?

To ensure sustained blood levels, you can take a daily dosage of 500 to 1500 mg divided between meals. It is advisable to begin with a lower dose and gradually increase, monitoring tolerance and gastrointestinal reaction. Combining berberine supplementation with a balanced diet and regular exercise can amplify its weight loss effects. 


Can I take berberine and metformin together for PCOS?

Combining berberine and metformin may be a great therapeutic approach to managing Polycystic Ovary Syndrome, especially in addressing weight gain caused by insulin resistance. Berberine and metformin individually contribute to improved insulin sensitivity, the most important aspect of PCOS management.

Berberine’s unique potential to activate brown adipose tissue and influence sirtuins complements metformin’s function in activating AMPK. This combined action can enhance glucose regulation and mitigate insulin resistance, which is an element of PCOS pathophysiology.


Is it safe to replace metformin with berberine?

Berberine has been recognized as a safe alternative to metformin. While both compounds exhibit potent effects on insulin regulation, berberine’s lower incidence of adverse reactions makes it a more attractive option. 


Can you take berberine forever?

The long-term safety of sustained berberine supplementation remains an area of ongoing clinical trials. Berberine has shown promise in managing weight and metabolic health. Extended and continuous use of berberine, however, raises questions about its impact on tolerance development and any unforeseen effects. 


Does berberine mess with hormones?

Research suggests that berberine may contribute to lower androgen hormone levels, which could be relevant in treating PCOS. Apart from androgens, berberine increases levels of leptin, a hormone that controls appetite and energy regulation.