Can You Take Berberine With Metformin?

In this blog, we will thoroughly discuss Berberine and Metformin, two compounds with significant medicinal properties. We will analyze their uses, benefits, and potential side effects, as well as their role in managing disorders like type 2 diabetes and their potential in oncology. We will also discuss the implications of using Berberine and Metformin together.
Greta Daniskova

Greta Daniskova

Greta is a BSc Biomedical Science student at the University of Westminster, London.

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What is Berberine?

Berberine is an alkaloid, a naturally occurring organic compound usually found within plants and usually having at least one nitrogen atom bound to a carbon-containing ring or ring system.

It is found in plants belonging to the genus Berberis, including Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric), Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense (Amur cork tree), Coptis chinensis (Chinese goldthread), Tinospora cordifolia, Argemone mexicana (prickly poppy), Eschscholzia californica (Californian poppy), and others [1, 2].

What does Berberine do?

This compound has been used in traditional Chinese and Ayurvedic medicine for centuries to manage a broad array of disorders. Nevertheless, multiple pharmacological activities of berberine elucidated in recent years revealed that this compound plays an important role at cellular and molecular levels. Berberine displays appreciable anti-inflammatory and antioxidant activities and has also been shown to exert neuroprotective and cardiovascular protective effects [1, 2].

It has also been included in clinical trials to normalise glucose and lipid metabolism disorders, through its lipid-lowering and insulin-resistance-improving (anti-diabetic) actions. Preliminary clinical evaluations also indicate a beneficial role of berberine in improving vascular health through its action to reduce endothelial inflammation, a potential cardioprotective feature, even in patients already having suffered a cardiovascular disorder [3, 4].

Berberine also shows promise in neurological health and has been found to provide some neuroprotection from multiple neurological disorders. It also has analgesic activity against diabetic and chemotherapy-induced neuropathy (nerve pain) and sciatic nerve injury-induced pain [5].

In oncology, berberine has been found to target oncogenic cell-signalling pathways in cancers of the oesophagus, breast, prostate, lung, liver, kidney and colon. In tumour-bearing mice, berberine exhibited both anti-cancer and anti-metastatic (ie, inhibiting the spread of tumours) effects [6].

What is Metformin?

Metformin (usually known as dimethylbiguanide) has been used as an oral antihyperglycemic drug, especially for the treatment of type 2 diabetes mellitus [1, 2, 3, 4, 5]; it is normally the first choice of multiple therapeutic agents against type 2 diabetes due to its safety, efficacy and tolerability [7, 8].

Metformin (1,1-dimethylbiguanide hydrochloride) is a biguanide derivative that can correct hyperglycemia by reducing hepatic glucose production and increasing glucose uptake into skeletal muscles [9, 10, 7, 11].

What does Metformin do?

The drug acts by increasing the body’s responsiveness to the glucose regulator insulin, which is secreted by the pancreas; it decreases the production of glucose by the liver and improves the efficiency with which the muscles pick up glucose emerging from the bloodstream [10, 12, 13, 11].

Besides its action (mainly) in the liver and muscles, and its ability to reduce peripheral insulin resistance, metformin has been shown to have an array of other favourable ‘side-effects’. This includes helping to maintain normal body weight and better lipid profiles – which further reduce the risk of cardiovascular diseases – and decreased risk of cancer [9, 10, 7, 13].

Moreover, there is anticancer activity of metformin since metformin can inhibit cancer cell growth. [14] There was a also benefit for polycystic ovary syndrome, insulin resistance syndromes, [7] and prediabetes. [15, 8] There are several benefits of metformin.

Side Effects of Berberine and Metformin Usage

Berberine and metformin are both used in the treatment of type 2 diabetes and have been shown to have significant effects on blood glucose levels. However, like all medications, they can also cause side effects.

Along with just about every other treatment on the planet, berberine is likely to cause some gastrointestinal discomfort. It can induce constipation in some while triggering diarrhoea in others. A randomised controlled trial on a berberine-based treatment for eight weeks found that only five of its 31 treated subjects suffered from diarrhoea, compared with 22 out of 28 of their untreated counterparts [16, 17].

While metformin also has potential side effects, including nausea, vomiting or diarrhoea [18] with long-term use, and a small chance of ‘lactic acidosis’, a metabolic complication with metformin usage, it has not so far been shown to prevent cancer [18].

Perhaps not surprisingly, given the therapeutic possibilities of each substance, the combination of berberine and metformin is associated with drug-drug interactions. For example, berberine can inhibit the absorption of metformin, which in turn influences the pharmacokinetics of the drugs [19, 20]. This may either augment or reduce the breath-saving effect – and, at the same time, may help spike the probability of side effects.

Can you take Berberine with Metformin?

For the treatment of diabetes, berberine and metformin are commonly used together as these two drugs separate and synergistically enhance each other’s hypoglycemic and insulin-sensitization effects [19, 20]. However, recent studies have suggested several drug-drug interactions between berberine and metformin, and the consequences of altered pharmacokinetics and pharmacodynamics of berberine and metformin remained underexplored as of yet [19, 20].

Berberine significantly reduced the maximum plasma concentration and urinary and bile excretion of metformin and led to an increased accumulation of metformin in kidney tissues [20]. Further research suggested that the inhibitory effects of berberine on the pharmacokinetics of metformin were mediated by the inhibition of organic cation transporters (OCT1 and OCT2) and multidrug and toxin extrusion 1 (MATE1) in the transport of metformin [19, 20].

By contrast, other studies involving berberine given alone or together with metformin showed that the two drugs enhanced each other’s benefits as well: berberine augmented the maximum plasma concentration and area under the curve of metformin [20], while an in-vivo study in db/db mice demonstrated that dual treatment with metformin presented a synergistic therapeutic effect with berberine through reduction of the blood glucose level and modulation of the composition of the gut microbiota [21].

Nevertheless, given the promising findings from some of these studies, and given how berberine appears to mimic some aspects of metformin’s effects, it’s reasonable to imagine that the two drugs could have some synergies, possibly magnifying certain benefits apart from weight loss. Still, before starting any new medications, berberine and metformin combined or not, individuals should consult with a healthcare provider.

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Greta Daniskova

Greta Daniskova

Greta is a 2nd-year student currently pursuing her Bachelor's Degree in Biomedical Sciences at the University of Westminster in London. Currently, in her second year of undergraduate studies, she exhibits a keen interest in the dynamic field of healthcare. With a focus on understanding the intricacies of human biology and disease mechanisms, Greta is driven by a desire to contribute to advancements in medical research and patient care.