Prediabetes FAQs

(Updated September 21, 2021)

“Prediabetes” is the term used for individuals with a slightly elevated A1C, impaired fasting glucose, and/or impaired glucose tolerance and indicates an increased risk for the future development of diabetes and cardiovascular disease.1,2 The chart below answers common questions about identifying and managing adults with prediabetes. See our diabetes resources (U.S. subscribers; Canadian subscribers) for more on potential side effects associated with prediabetes meds.

Question

Answer/Pertinent Information

What are risk factors for developing diabetes?

 

Examples of risk factors for developing DM may include:1,2,5,10,19

  • metabolic syndrome (considered a prediabetes equivalent)
  • physical inactivity or sedentary lifestyle
  • history of cardiovascular disease or a first-degree relative with type 2 DM
  • high-risk ethnicity (e.g., African American, Asian American, Aboriginal, Latino, Native American, Pacific Islander)
  • history of gestational DM, having a baby >9 pounds (4 kg), or polycystic ovary syndrome (PCOS)
  • hypertension or on medication for high blood pressure
  • low HDL cholesterol (ADA and AACE: HDL <35 mg/dL [0.9 mmol/L], CDA: HDL (males) <39 mg/dL [1 mmol/L]; HDL (females) <50 mg/dL [1.3 mmol/L])
  • high triglycerides (ADA and AACE: triglycerides >250 mg/dL [2.82 mmol/L];
    CDA: triglycerides >150 mg/dL [1.7 mmol/L])
  • A1C of >5.7% (≥6% Canada), IGT, or IFG (See definitions for IGT and IFG below.)
  • conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
  • taking medications associated with hyperglycemia (e.g., glucocorticoids, atypical antipsychotics, antiretrovirals)

 

How do experts differ regarding ADULT screening, diagnosis, and drugs of choicea for prediabetes?


ADA1

CDA2

AACE10,19

USPSTF5

Who to screen for prediabetes.

All adults 45 years and older

Adults at any age who are overweight or obese (BMI ≥25 kg/m2 or
≥23 kg/m2 in Asian Americans) with
≥1 risk factor.

Repeat screening at least every 3 years.

All adults 40 years and older

Can consider screening younger adults with risk factors for DM.

Repeat screening at least every 3 years.

All adults 45 years and older

Can consider screening younger adults with risk factors for DM.

Repeat screening at least every 3 years.

Adults between the ages of 35 and 70 years who are overweight or obese.

Consider screening younger adults with a lower BMI in high risk racial/ethnic groups, with a family history of DM, or a personal history of gestational DM or PCOS.

Repeat screening at least every 3 years.

 

Definition of prediabetes.

IFG: FPG between
100 and 125 mg/dL
(5.6 and 6.9 mmol/L)

OR

IGT: 2-h PG during
75-g OGTT between
140 and 199 mg/dL
(7.8 and 11 mmol/L)
OR

A1C: 5.7% to 6.4%

 

IFG: FPG between
110 and 125 mg/dL
(6.1 to 6.9 mmol/L)

OR

IGT: 2-h PG during
75-g OGTT between
140 and 199 mg/dL
(7.8 and 11 mmol/L)
OR

A1C: 6% to 6.4%

 

IFG: FPG between
100 and 125 mg/dL
(5.6 and 6.9 mmol/L)

OR

IGT: 2-h PG during
75-g OGTT between
140 and 199 mg/dL
(7.8 and 11 mmol/L)
OR

A1C: 5.5% to 6.4% (for screening only, must be confirmed with IFG or IGT for diagnosis)

 

 

IFG: FPG between
100 and 125 mg/dL
(5.6 and 6.9 mmol/L)

OR

IGT: 2-h PG during
75-g OGTT between
140 and 199 mg/dL
(7.8 and 11 mmol/L)
OR

A1C: 5.7% to 6.4%

 

 

Recommended drug of choice for prediabetes.

metformin

metformin

metformin

acarbose

Can consider a TZD or GLP-1 agonist with caution.

metformin

 

What is the role of diet and exercise in the treatment of prediabetes?

Encourage lifestyle and dietary changes including at least 150 minutes/week of moderate exercise (e.g., brisk walking).1,2,10

  • Lifestyle intervention resulting in weight loss of 5% to 10% and maintained for about three years prevented or delayed DM diagnosis (NNT = 7) compared to placebo [Evidence Level A-1].6,7
  • Patients with prediabetes adhering to a lifestyle intervention with goals of weight loss >5%, reduction in total fat intake to <30% of daily calories, saturated fat intake of <10% of daily calories, fiber intake of ≥15 g per 1,000 kcal daily, and exercise >4 hours per week over about three years prevented a diagnosis of DM (NNT ~8) [Evidence Level A-1].8

There are data to support recommending the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) diet, or Alternate Healthy Eating Index (AHEI) diet to delay or prevent the progression to DM. These diets differ from one another, but share dietary concepts such as eating whole grains, fruits, vegetables, nuts, legumes, olive oil, white meat, seafood, little or moderate alcohol, and limiting red meat, processed meats, and sugar-sweetened beverages.1,2

Diet and lifestyle interventions can prevent or delay progression to type 2 DM.5 Some experts try lifestyle interventions alone for three to six months before adding medications, while others may add medication right away.2

In the U.S., to find a registry of DM prevention programs in your area go to https://dprp.cdc.gov/Registry.

What is the role for metformin in the treatment of prediabetes?

Consider metformin for most patients with prediabetes to prevent progression to DM, especially in younger patients (<60 years old) with a history of gestational DM or with a BMI ≥35 kg/m2.1-3,5,10-12

  • Metformin 850 mg twice daily taken for about three years may prevent or delay DM diagnosis compared to placebo (NNT = 14) [Evidence Level A-1].6,7
  • Metformin at doses between 250 and 850 mg twice a day may delay or prevent type 2 DM in patients with IGT or IFG compared to placebo over a three-year period (NNT ranges from about 7 to 14 patients) [Evidence Level B-2].4

Preventing progression to DM with metformin seems sustainable with continued long-term therapy (e.g., 15 years).3

The effect of other doses in preventing progression to type 2 DM is not known, but start metformin at low doses and titrate slowly to improve tolerability.4

 

What is the role for acarbose in the treatment of prediabetes?

Consider acarbose in patients with prediabetes to prevent progression to DM.10

  • Treating about 12 patients who have IGT with acarbose for about three to 3.5 years prevents one case of DM.13,14
    • Of note, 31% of patients treated with acarbose discontinued therapy due to adverse effects, most commonly severe gastrointestinal effects (e.g., flatulence, diarrhea).13,14

 

What is the role for a thiazolidinedione in the treatment of prediabetes?

Rosiglitazone and pioglitazone appear to be effective at reducing the risk of developing DM.10,15,16

Safety concerns such as weight gain, heart failure and fracture risk, and a possible link to bladder cancer (pioglitazone) limit their use in the treatment of prediabetes.10

Experts who support the use of TZDs (e.g., pioglitazone, rosiglitazone) in the treatment of prediabetes, recommend saving them for patients who fail lifestyle changes, metformin, and acarbose due to safety concerns with their use.10

 

What is the role for glucagon-like peptide-1 agonists in the treatment of prediabetes?

GLP-1 agonists such as exenatide and liraglutide have been shown to reduce the prevalence of prediabetes over a one to two-year follow-up period.17,18

GLP-1 agonists require an injection and are much more expensive than other options, such as metformin.

Experts who support the use of GLP-1 agonists (e.g., exenatide, liraglutide) in the treatment of prediabetes, recommend saving them for patients who fail lifestyle changes, metformin, and acarbose due to a lack of long-term data supporting their use in prediabetes.10

 

Does screening for and treating prediabetes reduce cardiovascular disease?

Although screening for and treating prediabetes has been shown to delay progression to DM, this has NOT been shown to reduce cardiovascular mortality.5,9

  • There is NOT direct evidence that SCREENING for type 2 DM, IFG, or IGT among asymptomatic adults improves health outcomes.5,9
  • Data from at least 38 trials indicate behavioral and pharmacological interventions for prediabetes have no impact on all-cause mortality or cardiovascular events, though follow-up duration may have been too short to detect [Evidence Level B-2].5

 

  1. At the time of publication, there are not any FDA- or Health Canada-approved drugs for treating prediabetes.

Abbreviations: AACE = American Association of Clinical Endocrinologists; ADA = American Diabetes Association; CDA = Canadian Diabetes Association; DM = diabetes mellitus; FPG = fasting plasma glucose; GLP-1 = glucagon-like peptide-1; HDL = high-density lipoprotein; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; OGTT = oral glucose tolerance test TZD = thiazolidinedione; USPSTF = U.S. Preventive Services Task Force; 2-h PG = two-hour plasma glucose.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level

Definition

Study Quality

A

Good-quality patient-oriented evidence.*

  1. High-quality randomized controlled trial (RCT)
  2. Systematic review (SR)/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study

C

Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. http://www.aafp.org/afp/2004/0201/p548.pdf.]

References

  1. American Diabetes Association. Standards of Medical Care in Diabetes—2021. Diabetes Care 2021;44(Suppl 1):S1-S232.
  2. Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2018;42(Suppl 1):S1-S325.
  3. Diabetes Prevention Program Research Group. Long-term effects of metformin on diabetes prevention: identification of subgroups that benefited most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care 2019;42:601-8.
  4. Lily M, Goodwin M. Treating prediabetes with metformin: systematic review and meta-analysis. Can Fam Physician 2009;55:363-9.
  5. US Preventive Services Task Force, Davidson KW, Barry MJ.  Screening for prediabetes and type 2 diabetes:  US Preventive Services Task Force recommendation statement. JAMA 2021;326:736-43.
  6. Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
  7. Hamman RF, Wing RR, Edelstein SL, et al. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care 2006;29:2102-7.
  8. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among patients with impaired glucose tolerance. N Engl J Med 2001;344:1343-50.
  9. Selph S, Dana T, Blazina I, et al. Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive Services task force. Ann Intern Med 2015;162:765-76.
  10. Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes algorithm – 2020 executive summary. Endocr Pract 2020;26:107-39.
  11. The Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care 2012;35:723–30.
  12. Ratner RE, Christophi CA, Metzger BE, et al. Diabetes Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008;93:4774-9.
  13. Chiasson JL, Josse RG, Gomis R, et al. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002;359:2072-7.
  14. Chiasson JL, Josse RG, Gomis R, et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003;290: 486-94.
  15. DeFronzo RA, Tripathy D, Schwenke DC, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med 2011;364:1104-15.
  16. Zinman B, Harris SB, Neuman J, et al. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet 2010;376:103-11.
  17. Rosenstock J, Klaff LJ, Schwartz S, et al. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care 2010;33:1173-5.
  18. Astrup A, Rössner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009;374:1606-16.
  19. American Association of Clinical Endocrinologists. AACE diabetes resource center. Screening and monitoring of prediabetes. https://pro.aace.com/disease-state-resources/diabetes/depth-information/screening-and-monitoring-prediabetes. (Accessed February 17, 2021).

Cite this document as follows: Clinical Resource, Prediabetes FAQs. Pharmacist’s Letter/Prescriber’s Letter. March 2021. [370307]

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