How to increase metformin compliance in new diabetics

According to estimates from the Centers for Disease Control and Prevention, over 34 million people (more than 10% of the United States population) have diabetes mellitus. Another 88 million people (or 34.5% of the adult U.S. population) are pre-diabetic,[1] and will likely develop diabetes if nothing changes. Diabetes is a very common and debilitating disease that affects multiple body systems. Complications can include neuropathy, retinopathy, nephropathy, and cardiovascular disease, to name a few. As we know, diabetes can be fatal. Fortunately, however, we now have many interventions that can help decrease blood glucose levels, enhance insulin sensitivity, and improve our newly-diagnosed diabetic patients’ overall quality of life. As healthcare providers, we serve a unique role in that we can anticipate the challenges that our newly-diagnosed patients may face when implementing their treatment plans and help them avoid pitfalls (some of which I’ll mention in this article), so that they can live fulfilling lives in spite of their diagnoses.


Lifestyle Modifications: The Foundation of Optimal Glycemic Control and Wellness


In order to address diabetes mellitus type II most effectively, lifestyle modification must be at the foundation of the treatment plan. This includes optimizing sleep to 7-8 hours per day, helping each patient work toward achieving and maintaining a healthy weight, and making recommendations to help each patient choose the healthiest foods available to them and incorporate healthy movement into their daily routines. These lifestyle modifications have been demonstrated to result in reduced body weight, increased insulin sensitivity, and improved glycemic control.[2-4]

Other Minimally Invasive Non-Pharmaceutical Interventions

If these lifestyle modifications aren’t sufficient to normalize blood glucose levels, we’ll need to consider other modalities. This can include nutritional and/or botanical supplementation and pharmaceutical medication.


Here’s one example of a minimally invasive, non-pharmaceutical intervention: In a small study, an extract of the herb Gymnema sylvestre was given to participants as a supplement to conventional oral pharmaceutical medication for a total of 18-20 months.[5] At the start of the study, participants were stable on their medication; however, their blood glucose levels were incompletely controlled. By the end of the study, patients had lower blood glucose and hemoglobin a1c levels. Multiple patients were also able to decrease their medication dosages without a rebound increase in blood sugar. Five of the twenty-two patients included in the study were able to discontinue their pharmaceutical medication altogether, while still maintaining blood glucose homeostasis. Researchers concluded that these results suggest that beta cells may be regenerated/repaired in type-2 diabetic patients taking this particular extract of the Gymnema sylvestre plant.


While the results of the previously mentioned study were favorable, its methodology may cause us to question the researchers’ conclusions. In another small study, this one a randomized, double-blind, placebo-controlled trial, researchers found that Gymnema sylvestre administration in patients with impaired glucose tolerance led to improved insulin sensitivity, as demonstrated by improvements in 2-hour oral glucose tolerance and hemoglobin a1c levels. Researchers also noted improvements in patients’ lipid profiles.[6] Gymnema sylvestre is only one of multiple non-pharmaceutical agents that have been demonstrated in a growing body of research [7] to have favorable effects on glycemic control in pre-diabetic and/or diabetic patients.

Metformin as a First-line Pharmaceutical Treatment

If other modalities are not sufficient to maintain optimal glycemic control, we’ll need to progress to pharmaceutical medication. Since the 1950s, metformin has been used as the first line pharmaceutical treatment for type II diabetes. Its mechanism of action includes decreasing fasting plasma insulin concentrations, enhancing insulin sensitivity, enhancing peripheral glucose uptake, and decreasing hepatic glucose output.[8] The facts that metformin works, is fairly cost-effective, and hasn’t been found to cause weight gain all contribute to its status as a first-line therapy.

What Can We Do About Metformin Side Effects in our Newly-Diagnosed Diabetic Patients?

Unfortunately, however, the drug has a relatively high rate of discontinuation. This is due to the fact that some patients report gastrointestinal disturbances such as gastrointestinal upset, indigestion, and diarrhea on the drug. This side effect can be minimized by having patients take the drug with meals. Additionally, prescribing the extended release form of metformin instead of the immediate release form leads to a significant reduction in medication-related gastrointestinal concerns in many patients. Although the FDA has recently mandated a recall for some brands of extended release metformin due to concerns of nitrosodimethylamine contamination, they’ve also stated that the drugs involved in the recall represent only a small portion of the metformin available in the U.S. market.


Research suggests that long-term metformin therapy results in elevated homocysteine levels as well as decreased serum B12 levels and, in some cases, decreased folate.[9] Some researchers have further postulated that taking metformin for even a few months results in lower B12 and folate levels.[10] To reduce our patients’ risk of neuropathy and other unwanted effects, it may be of value to recommend that patients on metformin supplement with B12 (and potentially folate). Alternatively, B12 injections or including B12 as a part of an intravenous nutrient cocktail may be of significant value in patients with impaired nutrient absorption.


If you would like to learn more about incorporating intravenous nutrient therapy into your practice, click here.


The Importance of Education

Regardless of how you choose to manage your patients’ diabetes, I cannot stress the importance of patient education enough. Knowing that some patients experience adverse effects when starting metformin (or any therapeutic regimen), we should make sure that our patients understand why they should adhere to the treatment plans and how doing so will support their personal goals and their health and longevity. When patients understand why they’re doing something, they’re far more likely to stick with it.


1. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2020.

2. Yamanouchi, K., Shinozaki, T., Chikada, K., Nishikawa, T., Ito, K., Shimizu, S., Ozawa, N., Suzuki, Y., Maeno, H., & Kato, K. (1995). Daily walking combined with diet therapy is a useful means for obese NIDDM patients not only to reduce body weight but also to improve insulin sensitivity. Diabetes care, 18(6), 775–778. https://doi.org/10.2337/diacare.18.6.775

3. Shan, Z., Ma, H., Xie, M., Yan, P., Guo, Y., Bao, W., Rong, Y., Jackson, C. L., Hu, F. B., & Liu, L. (2015). Sleep duration and risk of type 2 diabetes: a meta-analysis of prospective studies. Diabetes care, 38(3), 529–537. https://doi.org/10.2337/dc14-2073

4. Colberg, S. R., Sigal, R. J., Fernhall, B., Regensteiner, J. G., Blissmer, B. J., Rubin, R. R., Chasan-Taber, L., Albright, A. L., Braun, B., American College of Sports Medicine, & American Diabetes Association (2010). Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes care, 33(12), e147–e167. https://doi.org/10.2337/dc10-9990

5. Baskaran, K., Kizar Ahamath, B., Radha Shanmugasundaram, K., & Shanmugasundaram, E. R. (1990). Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. Journal of ethnopharmacology, 30(3), 295–300. https://doi.org/10.1016/0378-8741(90)90108-6

6. Gaytán Martínez, L. A., Sánchez-Ruiz, L. A., Zuñiga, L. Y., González-Ortiz, M., & Martínez-Abundis, E. (2020). Effect of Gymnema sylvestre Administration on Glycemic Control, Insulin Secretion, and Insulin Sensitivity in Patients with Impaired Glucose Tolerance. Journal of medicinal food, 10.1089/jmf.2020.0024. Advance online publication. https://doi.org/10.1089/jmf.2020.0024

7. Ota, A., & Ulrih, N. P. (2017). An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes. Frontiers in pharmacology, 8, 436. https://doi.org/10.3389/fphar.2017.00436

8. Holman R. (2007). Metformin as first choice in oral diabetes treatment: the UKPDS experience. Journees annuelles de diabetologie de l'Hotel-Dieu, 13–20.

9. Sahin, M., Tutuncu, N. B., Ertugrul, D., Tanaci, N., & Guvener, N. D. (2007). Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. Journal of diabetes and its complications, 21(2), 118–123. https://doi.org/10.1016/j.jdiacomp.2005.10.005

10. Xu L, Huang Z, He X, Wan X, Fang D, Li Y. Adverse effect of metformin therapy on serum vitamin B12 and folate: short-term treatment causes disadvantages?. Med Hypotheses. 2013;81(2):149-151. doi:10.1016/j.mehy.2013.05.025

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