Berberine has a legacy that spans more than 2,200 years1 — this bitter, golden compound has been a cornerstone of traditional medicine across China, India, and the Middle East.2 Initially prized for its ability to combat infections and inflammation, berberine’s blood sugar-lowering effect was first noted in 500 AD, and was rediscovered in 1988 when diabetic patients given berberine to treat diarrhea experienced improved blood sugar control.3
This plant-derived alkaloid’s unique ability to impact everything from metabolic health to immune defenses has turned it into a subject of growing global interest, inspiring researchers to uncover even more of its wide-reaching benefits.
The Common Thread Behind Berberine’s Benefits
Before we look at the clinical studies, it helps to understand one well-established biological pathway that explains why berberine is so often discussed in metabolic research. In particular, alkaloids like berberine are capable of activating the AMP-activated protein kinase (AMPK) signaling pathway.4
The AMPK pathway is widely described in scientific literature as the body’s internal energy sensor. Its role is to monitor cellular energy levels and help regulate how the body uses and stores fuel. When cellular energy is low, AMPK becomes activated. Once turned on, it helps the body:
• Increase glucose (sugar) uptake into cells
• Promote fat burning over fat storage
• Reduce glucose production in the liver
• Lower inflammation and oxidative stress
This shared pathway is frequently highlighted in research on berberine and other natural compounds for their ability to support metabolic balance. If you want to know how this happens, read “The Neuroprotective Benefits of Berberine,” where I go into detail on the whole process of AMPK activation.
Berberine Safely Lowers Blood Sugar
A 2022 systematic review and meta-analysis published in Frontiers in Pharmacology examined 37 randomized controlled trials involving 3,048 patients with Type 2 diabetes to evaluate the glucose-lowering effects and safety of berberine.5 Researchers assessed berberine’s impact on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and two-hour postprandial blood glucose (2hPBG), as well as its safety profile compared to standard oral hypoglycemic agents (OHAs).
• Berberine significantly lowered blood sugar markers — Across all studies, berberine reduced FPG by an average of 0.82 mmol/L, HbA1c by 0.63%, and 2hPBG by 1.16 mmol/L. These improvements were statistically significant and consistent across subgroups with different baseline glucose levels.
• Effectiveness linked to baseline glucose — Patients with higher starting FPG and HbA1c saw greater reductions, suggesting berberine’s benefits are most pronounced in individuals with poorly controlled diabetes.
• Safety profile was favorable — Berberine did not increase the risk of adverse events or hypoglycemia. In fact, the risk of hypoglycemia was lower compared to some conventional drugs, likely because berberine’s insulin-stimulating effect is glucose-dependent.
Berberine Reduces Cholesterol and Has Protective Qualities
A separate earlier review in Acta Pharmaceutica Sinica B examined how berberine helps manage Type 2 diabetes and related metabolic complications. Researchers analyzed clinical trials, animal studies, and lab experiments to uncover its effects and mechanisms.6 They reviewed data from newly diagnosed Type 2 diabetes patients, individuals with poorly controlled diabetes, and animal models of both Type 1 and 2 diabetes.
• Berberine lowers blood sugar as effectively as metformin — In clinical studies, patients taking 0.5 grams of berberine two to three times daily showed significant drops in fasting blood glucose and A1c levels.
• It also improves cholesterol and lipid profiles — Multiple trials showed berberine reduced triglycerides by up to 35%, total cholesterol by 29%, and low-density lipoprotein (LDL) cholesterol by 25%. It also decreased fat buildup in the liver, helping patients with fatty liver disease.
• Berberine reduces sugar absorption in the gut — Acting as an alpha-glucosidase inhibitor, berberine slows carbohydrate breakdown and limits sugar spikes after meals. This gut-level action further helps with post-meal blood sugar control.
• May repair damaged insulin-producing cells or islets — In early-stage diabetes, berberine lowers insulin levels by improving sensitivity. In later stages, it may help restore beta-cell function, offering hope for patients with poor insulin production.
• Protects organs and reduces complications — In animal studies, berberine improved blood flow and reduced irregular heart rhythms by increasing nitric oxide (NO) production. It also lowered markers of kidney damage, suggesting protective effects against diabetic nephropathy.
Berberine Supports Weight Management
A 2023 review published in Biology examined how berberine influences fat storage. The study details mechanisms that could explain berberine’s potential to promote healthy weight management and enhance insulin sensitivity.7
• Berberine boosts GLP-1, a hormone linked to appetite and blood sugar — This alkaloid increases levels of glucagon-like peptide-1 (GLP-1), a gut hormone that helps the pancreas release insulin after meals and may promote feelings of fullness. Higher GLP-1 levels are associated with better blood sugar control and appetite regulation.
• It blocks new fat cell formation — Berberine reduces the activity of key transcription factors that normally turn precursor cells into fat cells. By interrupting this process, berberine may help prevent excess fat buildup, especially in organs like the liver.
• Calms inflammation from visceral fat — Excess belly fat releases inflammatory signaling molecules such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). These substances interfere with how insulin works. Berberine helps suppress their release, improving insulin response and metabolic balance.
• Slows fatty acid production — Berberine reduces the expression of enzymes like fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), which are involved in making new fat. This supports healthier lipid metabolism and may also help reduce fat accumulation in the liver.
For more insights on how berberine can be a helpful tool for reducing your weight, read “Is This a Natural Option for Harmful ‘Skinny’ Injections?”
A Promising Natural Berberine Derivative
In a randomized phase 2 trial published in JAMA Network Open in March 2025, researchers tested a compound, berberine ursodeoxycholate (HTD1801), for its ability to control blood sugar in overweight or obese adults with Type 2 diabetes. The study compared two doses of HTD1801 with placebo over a 12-week period.8
• High-dose HTD1801 lowered blood sugar significantly — The participants were randomly assigned to receive either a placebo, low-dose HTD1801 (500 milligrams twice daily), or high-dose HTD1801 (1,000 mg twice daily). The researchers found that patients taking 1,000 milligrams twice daily saw HbA1c drop by 1 percentage point, fasting glucose fall by about 20 mg/dL, and after-meal glucose decrease by about 23 mg/dL.
This effect was significantly greater than placebo and approached the efficacy of common diabetes drugs like metformin.
• More patients reached treatment targets — 55.9% of patients in the high-dose group achieved A1c below 7.0%, compared with just 15.2% in the placebo group. Nearly 30% of treated patients reached below 6.5%, a target often associated with remission thresholds. The participants given HTD1801 also had better insulin sensitivity and reduced total and LDL cholesterol levels, pointing to wider metabolic benefits beyond glucose control.
• An ideal solution for patients seeking natural options — HTD1801 combines berberine with ursodeoxycholate, a bile acid that helps absorption and supports liver health. If confirmed in larger studies, it may be recommended to people who prefer plant-based therapies or can’t tolerate metformin.
Metformin vs. Berberine — Similarities and Differences
In a pilot clinical study published in Metabolism (2008), researchers from Shanghai Jiaotong University and Pennington Biomedical Research Center investigated how berberine compares to metformin, one of the most common diabetes drugs prescribed today.9 Researchers enrolled 84 adults with Type 2 diabetes: 36 who were newly diagnosed and received either berberine or metformin, and 48 whose blood sugar remained high despite existing treatments and received berberine as an add-on.
• Berberine matched metformin in lowering blood sugar — Among the newly diagnosed group, berberine led to significant improvements: HbA1c dropped from 9.5% to 7.5%, fasting glucose from 10.6 to 6.9 mmol/L, and post-meal glucose from 19.8 to 11.1 mmol/L — nearly identical to the reductions seen with metformin.
• Insulin resistance improved dramatically — In a second group of 48 patients with poorly controlled diabetes, adding berberine to their existing treatments lowered fasting insulin by 28% and improved insulin sensitivity (HOMA-IR) by 45%, suggesting berberine enhances how well the body uses insulin.
• Comparable safety profile with some GI side effects — About one-third of patients reported mild digestive issues like bloating or diarrhea, mostly in the first few weeks. No liver or kidney damage was observed. The researchers noted that reducing the dose from 500 to 300 mg per dose helped most patients tolerate it better.
• A potential new class of oral anti-diabetic agents — Unlike metformin and sulfonylureas, berberine is chemically distinct and works through different mechanisms. The authors suggest berberine may improve glucose metabolism by increasing glycolysis and reducing sugar absorption in the gut — offering a complementary or alternative approach to current drugs.
Berberine and metformin both help lower blood sugar, but they work in slightly different ways. This table breaks down how they compare — from how well they lower A1c and cholesterol, to side effects and regulatory status:
| Feature | Berberine | Metformin |
|---|---|---|
| How it works | Helps cells burn sugar and fat (AMPK); affects gut and sugar breakdown | Reduces liver sugar production; also activates AMPK and affects the gut |
| Average A1c drop | About 0.6% on average; larger drops in newly diagnosed patients | About 1.0% to 2.0%, depending on the dose |
| Cholesterol effects | Can lower triglycerides and total cholesterol in some people | Modest drops in triglycerides and LDL cholesterol |
| Digestive side effects | Some people report bloating or constipation; newer forms cause fewer issues | Nausea and diarrhea are common at first, but often improve with gradual dosing |
| Evidence strength | Many small to medium studies; new versions still in development | Backed by decades of strong clinical trials and real-world data |
Although metformin remains the most commonly prescribed oral medication for managing Type 2 diabetes today, there’s emerging research about its side effects, some of which are concerning. For example, long-term use has been associated with vitamin B12 deficiency. Recent research has also demonstrated how taking metformin can reduce the benefits of exercise.
What the Research Says So Far
Across the discussed studies, berberine has consistently showed its ability to lower blood sugar, improve insulin sensitivity, and reduce LDL cholesterol and triglycerides — benefits that rival some prescription drugs. While not yet a mainstream therapy in Western medicine, it holds strong appeal for those exploring plant-based alternatives or complementary treatments.
The table below summarizes key outcomes from five major studies evaluating berberine’s impact on blood sugar, insulin resistance, lipids, and safety profile:
| What was measured | Study type and details | Results (effect size and timeframe) | Source |
|---|---|---|---|
| HbA1c (long-term blood sugar control) | Meta-analysis of 37 RCTs (3,048 patients) | Average drop of 0.63% in HbA1c; stronger effects in people with higher baseline levels | Frontiers in Pharmacology (2022)10 |
| Fasting and post-meal blood sugar | Same meta-analysis as above | Fasting glucose dropped by 0.82 mmol/L (~15 mg/dL); post-meal sugar by 1.16 mmol/L | Frontiers in Pharmacology (2022)11 |
| Newly diagnosed Type 2 diabetes | 13-week RCT; 500 mg berberine 3x/day | HbA1c dropped by 2%; fasting glucose by 3.8 mmol/L; post-meal glucose by 8.8 mmol/L | Metabolism Journal (2008)12 |
| Berberine derivative (HTD1801) | 12-week Phase 2 RCT; 1,000 mg twice daily | HbA1c dropped by 1.0%; fasting glucose dropped ~20.5 mg/dL; improved cholesterol; fewer GI side effects | JAMA Network Open (2025)13 |
| Cholesterol and triglycerides | Clinical reviews and human trials | Triglycerides ↓ up to 35%; LDL ↓ 25%; total cholesterol ↓ 29%; less liver fat (NAFLD improvement) | Acta Pharmaceutica Sinica B14 |
How To Take Berberine
Berberine can be an effective aid for controlling blood sugar and cholesterol, but to achieve optimal results, proper intake is important. Like any supplement, the way you take it and the brand you select can significantly impact its effectiveness.
1. Don’t take it on an empty stomach — Studies recommend taking berberine three times daily with meals — breakfast, lunch, and dinner. Consuming it with food can help lessen digestive discomfort and enhance absorption.15
2. Titrate slowly for better gut tolerance — If you’re new to berberine, begin with a small dose, such as 300 to 500 mg once daily, and gradually increase to two or three times per day as tolerated.16
3. Look for third-party testing — Select supplements that show the United States Pharmacopeia (USP) or NSF International certification or provide a Certificate of Analysis (COA) from an accredited laboratory. These documents verify the product’s purity, potency, and absence of contaminants like lead and harmful bacteria.17
4. Talk to your doctor — Even though berberine is generally safe, it can interact with medications, especially those used to treat blood sugar, blood pressure, or cholesterol. If you’re currently taking prescription drugs or managing a condition like diabetes, kidney disease, or liver issues, talk to your doctor before adding berberine to your routine.18
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4 safety tips when taking berberine |
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Is Berberine Safe for Everyone?
Berberine can offer big benefits, but just like any supplement, it’s not one-size-fits-all. Before you add it to your daily routine, here are a few things to watch out for to make sure it’s the right fit for your body.19
• Digestive issues are the most common side effect — Many people notice common symptoms like nausea, bloating, constipation, or diarrhea when they begin.
• Avoid if pregnant, breastfeeding, or very young — Berberine isn’t recommended for pregnant or nursing women, as it may cross the placenta or enter breastmilk. It should also not be used in infants or young children, due to possible safety concerns in developing systems.
• Be careful if you take other medications — Berberine can interact with drugs like metformin, blood thinners, cyclosporine, and statins. It uses some of the same liver enzymes as these medications, which can alter their processing.
Berberine Offers Promise for Diabetes Care
Berberine may play a valuable role in supporting Type 2 diabetes, however, many trials to date have been short-term, typically lasting no longer than 12 weeks.20 To understand how berberine works over the long run, scientists are calling for larger, longer clinical trials.
Improved absorption is another research priority. Some newer formulations, such as HTD1801, combine berberine with bile acids to increase bioavailability and reduce side effects. Early trials show encouraging results, but these need confirmation in larger studies.21 Once more research has been conducted, berberine could evolve from a niche supplement into a meaningful part of Type 2 diabetes management.22
Frequently Asked Questions (FAQs) About Berberine and Diabetes
Q: Does berberine lower A1c in people with Type 2 diabetes?
A: Yes. In a 2022 meta-analysis of 37 randomized controlled trials, berberine lowered HbA1c (hemoglobin A1c) by an average of 0.63 percentage points. People with higher starting A1c saw even greater drops.
Q: How does berberine work to improve insulin resistance?
A: Berberine activates AMPK (AMP-activated protein kinase), an enzyme that helps cells burn sugar and fat for energy. It also reduces liver sugar production and improves the function of your gut and mitochondria.
Q: Berberine vs. metformin — Which is more effective for blood sugar?
A: Metformin is the most widely used diabetes medication approved by the U.S. Food and Drug Administration (FDA). It usually lowers HbA1c by 1 to 2%. Berberine may show similar results in some cases — especially in newly diagnosed patients.
Q: What dose was used in studies, and how should it be taken?
A: Most clinical trials used 500 milligrams of berberine, taken three times a day with meals. If side effects like gas or diarrhea occurred, the dose was reduced to 300 mg per meal.
Q: How quickly does berberine start working?
A: Changes in FPG and HbA1c were often seen by weeks 4 or 5. Most studies saw full benefits after 12 to 13 weeks of consistent use.
Q: Can you combine berberine with prescription diabetes drugs?
A: Some studies added berberine to existing medications and saw extra benefits. But because it can further lower blood sugar, always speak with your doctor to avoid hypoglycemia or low blood sugar.
Q: Does berberine help with weight loss or cholesterol?
A: Berberine lowered LDL, triglycerides, and total cholesterol in many studies. While weight-loss effects varied, it reduced fat buildup and inflammation in some trials.
