Researchers tested whether a natural supplement made from citrus fruits could help people with prediabetes (early warning signs of diabetes) who were already taking metformin, a common diabetes medication. Over 12 weeks, people who took the citrus supplement along with metformin showed better blood sugar control, less inflammation in their bodies, and modest weight loss compared to those taking metformin alone. The citrus supplement appeared to work by preserving helpful hormones that regulate blood sugar and reducing harmful inflammation. While these results are promising, researchers emphasize that more long-term studies are needed before making this a standard treatment recommendation.

The Quick Take

  • What they studied: Whether adding a natural citrus flavonoid supplement (a compound found in citrus fruits) to metformin therapy could improve blood sugar control and overall metabolic health in people with prediabetes
  • Who participated: Adults with prediabetes who were already taking metformin medication. The study lasted 12 weeks and used a double-blind design, meaning neither the participants nor the researchers knew who received the real supplement versus a placebo (fake pill)
  • Key finding: People taking the citrus supplement showed a 5% reduction in blood sugar levels two hours after eating, maintained healthy levels of a hormone called GLP-1 that helps control blood sugar, and experienced a 12% reduction in inflammation markers. The placebo group’s GLP-1 levels actually declined
  • What it means for you: If you have prediabetes and take metformin, a citrus-based supplement may help your body manage blood sugar more effectively and reduce inflammation. However, this is early-stage research, and you should discuss any supplement with your doctor before starting, as more long-term studies are needed to confirm these benefits

The Research Details

This was a randomized controlled trial, which is considered one of the strongest types of medical research. Participants were randomly assigned to receive either metformin plus a 250 mg daily citrus flavonoid supplement or metformin plus a placebo (inactive pill). Neither the participants nor the researchers knew who received which treatment until the study ended—this “double-blind” approach prevents bias from influencing results. The study lasted 12 weeks, and researchers measured multiple health markers including blood sugar levels, inflammation, antioxidant capacity (the body’s ability to fight harmful molecules), body weight, and blood pressure.

The citrus supplement used in this study contained bioflavonoids, which are natural compounds found in citrus fruits that have antioxidant and anti-inflammatory properties. Researchers chose to study this combination because metformin, while effective, sometimes causes side effects or becomes less effective over time. They hypothesized that adding natural compounds with anti-inflammatory properties might enhance metformin’s benefits and reduce some of its drawbacks.

Participants underwent testing at the beginning and end of the 12-week period. Blood tests measured fasting glucose (baseline blood sugar), glucose levels two hours after eating (postprandial glucose), insulin resistance, GLP-1 hormone levels, inflammation markers, and antioxidant capacity. Researchers also measured body composition, blood pressure, and dietary intake to get a complete picture of metabolic health.

This research approach is important because it tests a real-world scenario: what happens when you combine a conventional medication (metformin) with a natural supplement. The randomized, double-blind design minimizes bias and provides strong evidence about whether the supplement actually works or if improvements are just placebo effects. By measuring multiple health markers—not just blood sugar—researchers could understand how the supplement affects the whole body’s metabolism, inflammation, and oxidative stress. This comprehensive approach helps determine whether the supplement is truly beneficial or just creates the appearance of benefit

This study has several strengths: it’s a randomized controlled trial (the gold standard for medical research), it’s double-blind (preventing bias), it was published in a peer-reviewed journal (Frontiers in Nutrition), and it was registered in a clinical trials database (NCT06005142), which increases transparency. However, the sample size was not specified in the abstract, which makes it harder to assess statistical power. The 12-week duration is relatively short for evaluating long-term benefits of a supplement. The study was conducted in a controlled setting, which may not reflect real-world conditions where people have varying diets, exercise habits, and medication adherence

What the Results Show

The most important finding was that people taking the citrus supplement showed improved blood sugar control after meals. Specifically, their blood glucose levels measured two hours after eating were 5% lower than the placebo group. This is significant because high blood sugar spikes after meals are a key problem in prediabetes and diabetes.

Another major finding involved a hormone called GLP-1, which helps your body regulate blood sugar naturally. In the supplement group, GLP-1 levels stayed stable or improved, while in the placebo group, GLP-1 levels actually declined. This suggests the citrus supplement helps preserve your body’s natural blood sugar-regulating mechanisms.

The supplement also reduced inflammation throughout the body. TNF-alpha, a marker of inflammation, decreased by 12% in the supplement group. Inflammation is important because it contributes to insulin resistance (when your body doesn’t respond well to insulin) and other metabolic problems. Additionally, the supplement increased the body’s antioxidant capacity by 7.5%, meaning the body became better at fighting harmful molecules that damage cells.

Participants in the supplement group also experienced modest but meaningful improvements in body composition: small reductions in body weight, fat mass, and BMI (body mass index). Systolic blood pressure (the top number in a blood pressure reading) decreased by 4%, which researchers believe was related to improved antioxidant status and higher potassium intake from the supplement

Beyond the primary outcomes, the study found that the citrus supplement appeared to be well-tolerated with no serious adverse effects reported. The supplement’s benefits seemed to work through multiple mechanisms: reducing inflammation, improving antioxidant defenses, and preserving hormonal signals that regulate blood sugar. The modest weight loss and blood pressure reduction, while not dramatic, are clinically meaningful because even small improvements in these areas reduce the risk of developing type 2 diabetes and cardiovascular disease. The fact that multiple health markers improved simultaneously suggests the supplement has broad metabolic benefits rather than affecting just one pathway

This research builds on growing evidence that natural polyphenols (plant compounds with antioxidant properties) may help manage blood sugar and reduce diabetes risk. Previous studies have suggested that citrus flavonoids have anti-inflammatory and antioxidant effects, but this is one of the first studies to specifically test whether they enhance metformin therapy in prediabetic patients. The findings align with other research showing that combining conventional medications with targeted nutritional interventions may produce better outcomes than medication alone. However, most previous studies on citrus flavonoids were smaller or conducted in laboratory settings, so this controlled trial provides stronger evidence for human benefit

Several important limitations should be considered. First, the abstract doesn’t specify how many people participated, making it impossible to assess whether the study had enough participants to detect real effects reliably. Second, the study lasted only 12 weeks, which is relatively short for evaluating long-term benefits of a supplement—we don’t know if improvements continue, plateau, or reverse after stopping the supplement. Third, the study doesn’t describe the participants’ baseline characteristics (age, gender, ethnicity, severity of prediabetes), which could affect how well results apply to different populations. Fourth, the study measured only immediate effects; we don’t know about long-term outcomes like whether the supplement actually prevents progression to type 2 diabetes. Finally, the study was conducted in a controlled research setting where participants’ diets and behaviors were likely monitored, which may not reflect real-world conditions where people have more variable lifestyles

The Bottom Line

Based on this research, citrus flavonoid supplements may be worth discussing with your doctor if you have prediabetes and are taking metformin, particularly if you’re interested in natural approaches to enhance your treatment. However, confidence in this recommendation is moderate because the study was relatively short and we need more long-term research. Do not use a supplement as a replacement for metformin or other prescribed medications. If you decide to try a citrus supplement, work with your healthcare provider to monitor your blood sugar, inflammation markers, and overall health. The supplement appears safe based on this study, but individual responses vary

This research is most relevant for adults with prediabetes who are already taking metformin and want to optimize their blood sugar control. It may also interest people with prediabetes who haven’t started metformin yet and want to explore natural options (though they should discuss this with their doctor). People with type 2 diabetes might benefit, but this study specifically tested prediabetic patients, so results may differ. This research is less relevant for people without blood sugar problems or those not taking metformin. Anyone with kidney disease, liver disease, or those taking medications that interact with supplements should consult their doctor before starting any new supplement

Based on this 12-week study, you might expect to see improvements in blood sugar control within 4-6 weeks if the supplement works for you, with more noticeable benefits by 12 weeks. However, individual responses vary significantly. Weight loss and blood pressure improvements were modest in this study, so don’t expect dramatic changes. The anti-inflammatory benefits may take several weeks to accumulate. It’s important to note that this study only measured effects over 12 weeks, so we don’t know what happens with longer-term use. You should give the supplement at least 8-12 weeks of consistent use while monitoring your blood sugar before deciding whether it’s working for you

Want to Apply This Research?

  • Track your fasting blood glucose (morning blood sugar before eating) and postprandial glucose (blood sugar 2 hours after meals) weekly using a glucose meter or continuous glucose monitor. Record these in your app along with the date and time. This directly mirrors what the research study measured and will show whether the supplement is helping your blood sugar control. Aim to see a gradual downward trend over 8-12 weeks
  • Start taking a citrus flavonoid supplement (250 mg daily, as used in the study) alongside your metformin, with your doctor’s approval. Log each dose in your app to track adherence. Simultaneously, log your meals and note any changes in how you feel after eating (energy levels, hunger, cravings). The app can help you identify patterns between supplement use, diet, and blood sugar readings
  • Create a dashboard in your app that tracks four key metrics weekly: fasting glucose, postprandial glucose, body weight, and blood pressure. Set a 12-week goal to assess whether the supplement is working for you. If you see improvements in 2-3 of these metrics by week 12, continue the supplement and discuss long-term use with your doctor. If you see no improvement, discuss alternatives with your healthcare provider. Continue monitoring even after 12 weeks to ensure benefits persist and to catch any changes that might require adjusting your treatment plan

This research summary is for educational purposes only and should not be considered medical advice. The study shows promising results for citrus flavonoid supplements as an adjunct to metformin in prediabetic patients, but it is a single 12-week trial and more long-term research is needed. Do not start, stop, or change any diabetes medications or supplements without consulting your healthcare provider first. Individual responses to supplements vary, and supplements are not regulated by the FDA in the same way as medications. If you have prediabetes, kidney disease, liver disease, or take other medications, discuss any supplement with your doctor before use to check for interactions and safety. This summary does not replace professional medical advice, diagnosis, or treatment.