Is Medication Appropriate for Prediabetes?
By Lisa Andrews, MEd, RD, LD
We’ve all likely encountered a family member, friend, or client who’s been diagnosed with prediabetes, a condition that increases the risk of type 2 diabetes and vascular complications, including heart disease.
According to the American Diabetes Association (ADA), roughly 10% of people with prediabetes progress to type 2 diabetes every year.1 Feelings of fear, shame, and guilt can be common. Patients often think it’s their fault, and the thought of taking medication can make them feel like a failure. But is medication necessary in prediabetes treatment?
According to the ADA, the most common way to define prediabetes is by HbA1c—a measure of average blood sugar over a two- to three-month window of time. A normal level is below 5.7%. Prediabetes is defined as a level between 5.7% and 6.4%, with 6.5% and above being a diagnosis of diabetes. A person doesn’t need to fast to have their HbA1c checked.2
Fasting plasma glucose (FPG) is checked after a person has been fasting for a minimum of eight hours. A normal FPG is below 100 mg/dL, while values between 100 and 125 mg/dL indicate prediabetes. A type 2 diabetes diagnosis is made if the FPG level is 126 mg/dL or higher.2
The oral glucose tolerance test (OGTT) often is completed during pregnancy to diagnose gestational diabetes but may be used to diagnose type 2 diabetes. Blood sugar levels are checked before and after consuming a super sweet beverage. A normal OGTT level is below 140 mg/dL; prediabetes is between 140 and 199 mg/dL; and readings above 200 mg/dL are diagnosed as diabetes.2
Lifestyle vs Metformin
While diet and regular physical activity are considered firstline (and ongoing) treatments for prediabetes, medication also may be recommended. The most commonly used medication for prediabetes is metformin, although it hasn’t been FDA approved for use in prediabetes treatment.3
Metformin is an oral medication that dates back to 1929, but it wasn’t officially used in the United States until 1995. It helps regulate blood sugar by limiting the amount of glucose released by the liver and making cells more responsive to insulin.3 It also improves peripheral glucose uptake and use by cells. The ADA advises the use of metformin in the following conditions:
• age younger than 60;
• both impaired fasting glucose and impaired glucose tolerance; and
• other risk factors such as HbA1c >6%, hypertension, low HDL cholesterol, elevated triglycerides, or a family history of diabetes in a first-degree relative.4
The largest randomized controlled trial of metformin in those with prediabetes is the 2002 Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP), which found that subjects using intensive lifestyle interventions (diet counseling and exercise) compared with those who received only metformin had fewer cases of diabetes within three years. However, metformin still was effective.5,6
At the end of the DPP, diabetes incidence decreased 31% in subjects who continued metformin use compared with placebo after roughly a three-year follow up. This effect was seen in those who were obese, had elevated fasting blood glucose, or had experienced gestational diabetes.6
Decreased progression to diabetes in the DPP was linked with a 28% lower risk of microvascular complications across treatment groups at 15 years. Recent data suggest metformin use in men may reduce the development of atherosclerosis.7
A more recent study of Hispanic women had similar results. In a 12-month study comparing an intensive lifestyle intervention with medication use, those who lost roughly 5% of their body weight within five months had more normal blood sugar levels compared with those taking only metformin (39% vs 25%, respectively).8
Pros of Metformin Use
In addition to lowering blood sugar, some patients may experience mild weight loss with metformin use. As obesity and overweight are risk factors for diabetes, those with prediabetes may welcome weight loss to further reduce their risk.
A recently discovered benefit to metformin use in epidemiologic studies is reduction in breast cancer incidence and mortality among patients with type 2 diabetes. Metformin reduces the development of insulin resistance in breast cancer cells, allowing chemotherapy to work along with metformin.9
In other studies, researchers have observed a decrease in cognitive decline in subjects older than 60 using metformin. A 2016 meta-analysis of studies of more than 500,000 subjects found that use of metformin or thiazolidinediones had a reduction in the incidence of dementia. However, a Mayo Clinic study on aging found the opposite. The study compared metformin use with other antidiabetes medications in more than 500 older adults with diabetes and without dementia. Over a three-year period, metformin use was associated with an increase in mild cognitive decline.10
Cons of Metformin Use
While there are benefits to using metformin, side effects may include nausea, flatulence, or diarrhea. Patients can mitigate these side effects by taking the medication with food (or after a meal). Unlike other diabetes medications, metformin doesn’t cause severe hypoglycemia or impact insulin levels. In rare cases, metformin can cause lactic acidosis, which is more commonly seen in those with progressive renal failure. Long-term use is linked with vitamin B12 deficiency.11
Diet Trends for Prediabetes
Dietary and lifestyle interventions, such as intermittent fasting, low-carbohydrate, Mediterranean, DASH, and ketogenic diets may be advised for those with prediabetes. Intermittent fasting (without weight loss) has been shown to improve metabolic parameters. In a study by Sutton and colleagues, men using early time-restricted feeding, a form of intermittent fasting that entails eating meals within six hours and dinner before 3 PM, saw improved insulin sensitivity, beta-cell responsiveness, blood pressure, oxidative stress, and appetite. Despite reduced food intake later in the day, subjects didn’t experience hunger.12
Low-carb diets, once considered a fad, are a feasible way to manage prediabetes and diabetes. In fact, the ADA accepts low-carbohydrate eating patterns to manage weight and blood sugar. Diets that reduce carb intake to 40% of calories may be considered “low carb,” though ketogenic diets are much lower in carbohydrates.13
A 2019 review study on low-carb and keto diets in those with type 2 diabetes found that while they may aid in weight management and glycemic control, these types of diets could raise CVD risk due to their high fat content. Long-term adherence to these diets also may be an issue and needs further study.14
In other research, it’s been suggested that the DASH and Mediterranean diets may aid in the prevention and reversal of prediabetes. A meta-analysis of prospective studies evaluating various diets in diabetes prevention found that the DASH and Mediterranean diets and other healthful eating patterns (ie, low saturated fat and reduced refined sugar), decrease the risk of future diabetes by 29%.15 These diets also may help with weight loss, which has shown to improve insulin resistance.
Diet modification including moderate carbohydrate restriction and regular physical activity still will remain important in the prevention and treatment of diabetes. While medication may be used safely in most patients with prediabetes, there are pros and cons for individuals to consider.
— Lisa Andrews, MEd, RD, LD, is a consultant dietitian and freelance writer with Dietitian Pros, premier nutrition staffing. Dietitian Pros provides nationwide class-leading nutrition staffing services and recruits registered dietitians to serve in temporary, part-time or full-time positions.
1. Brannick B, Dagogo-Jack S. Prediabetes and cardiovascular disease pathophysiology and interventions for prevention and risk reduction. Endocrinol Metab Clin North Am. 2018;47(1):33-50.
2. American Diabetes Association. Classification and diagnosis of diabetes. Standards of medical care in diabetes — 2018. Diabetes Care. 2018;41(Suppl 1):S13-S27.
3. The origins of metformin. Diabetes Forecast website. http://www.diabetesforecast.org/2010/dec/the-origins-of-metformin.html. Published December 2010.
4. Khardori R. Type 2 diabetes mellitus treatment & management. Medscape website. https://emedicine.medscape.com/article/117853-treatment#d25. Updated July 28, 2020.
5. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
6. Herman WH, Pan Q, Edelstein SL, et al. Impact of lifestyle and metformin interventions on the risk of progression to diabetes and regression to normal glucose regulation in overweight or obese people with impaired glucose regulation. Diabetes Care. 2017;40(12):1668-1677.
7. Aroda VR, Knowler WC, Crandall JP, et al. Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study. Diabetologia. 2017;60(9):1601-1611.
8. O’Brien MJ, Perez A Scanlan AB, et al. PREVENT-DM comparative effectiveness trial of lifestyle intervention and metformin. Am J Prev Med. 2017;52(6):788-797.
9. Roshan MHK, Shing YK, Pace NP. Metformin as an adjuvant in breast cancer treatment. SAGE Open Med. 2019;7:2050312119865114.
10. Ye F, Luo YJ, Xiao J, U NW, Yi G. Impact of insulin sensitizers on the incidence of dementia: a meta-analysis. Dement Geriatr Cogn Disord. 2016;41(5-6):251-260.
11. Aroda VR, Edelstein SL, Goldberg RB. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761.
12. Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. 2018;27(6):1212-1221.e3.
13. Hite A. American Diabetes Association endorses low-carb diet as option. Diet Doctor website. https://www.dietdoctor.com/american-diabetes-association-endorses-low-carb-diet-as-option. Published April 25, 2019.
14. Bolla AM, Caretto A, Laurenzi A, Scavini M, Piemonti L. Low-carb and ketogenic diets in type 1 and type 2 diabetes. Nutrients. 2019;11(5):962.
15. Esposito K, Chiodini P, Maiorino MI, et al. Which diet for prevention of type 2 diabetes? A meta-analysis of prospective studies. Endocrine. 2014;47(1):107-116.