Undertreating Prediabetes Comes at a Cost

Problems include excessive costs, increased risk for complications later and more.

NEW ORLEANS — It may be time to rethink management of prediabetes, according to some experts.

Currently, there are no agents approved by the Food and Drug Administration (FDA) for treating prediabetes. Yet, an estimated 79 million people in the U.S. have prediabetes and 40% to 50% of those will progress to type 2 diabetes.

Consequently, endocrinologists and other health care providers may want to be more aggressive in managing prediabetes once it is diagnosed, researchers said at AADE 2015, the annual meeting of the American Association of Diabetes Educators.

“We have interacted with many providers in the past who did not see management of prediabetes as a patient-care priority. They felt that there wasn’t much to do until the formal diagnosis of diabetes was made. It is important to appreciate the continuum of diabetes,” clinical pharmacist Jeremy Johnson, PharmD, MBA, of the Southwestern Oklahoma State University College of Pharmacy in Waterford, said during a presentation.

“Once a patient has prediabetes, the pathophysiologic process that builds to what we have defined as ‘diabetes’ has begun. Prevention or delay, of disease progression is the goal.”

Johnson along with clinical pharmacist Katherine O’Neal, PharmD, MBA, BCACP, CDE, BC-ADM, AE-C, of the University of Oklahoma College of Pharmacy and School of Community Medicine in Tulsa, discussed the importance of addressing prediabetes early.

With prediabetes, many of the pathophysiologic abnormalities already exist, O’Neal said, and upon diagnosis, approximately 10% to 15% of patients show signs of microvascular complications.

Currently, the American Diabetes Association (ADA) recommends lifestyle changes as first-line therapy for prediabetes

“While lifestyle modifications are extremely important, at times, drug therapy may be of benefit or necessary,” Johnson told Endocrinology Advisor. “While many providers may be familiar with lifestyle recommendations and use of metformin as recommended by the American Diabetes Association, other options are often needed.”

Johnson and O’Neal presented a review of the current literature on the effectiveness of non-traditional agents in the management of prediabetes. They said it is now the responsibility of health care providers to share with patients who have prediabetes all available options to help delay the progression to diabetes.

Underdiagnosing and undertreating prediabetes is having an enormous economic, clinical and humanistic impact, Johnson said.

In 2012, the U.S. economic burden of diabetes exceeded $322 billion in excess medical costs and lost productivity. From 2007 to 2012, the cost of prediabetes increased to $44 billion, representing a 74% increase, according to O’Neal.

She said clinicians need to tailor therapy to individual patients and their needs. It is important to take into consideration whether lifestyle changes are working and whether a medication has the proper characteristics to best fit the needs of the patient. Additionally, clinicians need to address issues of drug tolerability, costs and whether a patient has a strong family history of diabetes.

Studies show that patients with prediabetes have an increased risk for developing type 2 diabetes, heart disease and stroke. Currently, the national prevalence of diabetes is estimated to be 11.3% (25.6 million) in adults over the age of 20 and 26.9% (10.9 million) in adults over the age of 65. 

The national prevalence of prediabetes is estimated to be 35% (estimated 79 million) in adults aged 20 years and older, and 50% in adults aged 65 years and older.

During early progression of prediabetes, there tends to be an increase in visceral fat deposition as well as an increase in fat in the liver, muscle and pancreas. Johnson said increased fat in these areas will lead to more lipolysis and a generation of free fatty acids (FFAs).

The effects of excessive FFAs harm the liver, and FFAs act as precursors to glucogenesis and a host of other problems that lead to impaired insulin secretion, according to Johnson. Insulin resistance begins when the pancreas compensates by producing enough extra insulin to achieve normoglycemia. Eventually, the beta cells can no longer compensate and hyperglycemia is the result.

Johnson said prediabetes is often not diagnosed until complications present and approximately one-fourth are undiagnosed. Therefore, he suggests that clinicians should consider screening asymptomatic adults if they are overweight (BMI of at least 25) or have one or more risk factors.

He also recommends women be screened if they delivered a baby weighing more than 9 lb, had gestational diabetes or have polycystic ovary syndrome (PCOS).

At present, the ADA recommends weight loss if necessary, increasing physical activity to at least 150 minutes per week of moderate physical activity and the addition of metformin if the patient:

  • Has impaired glucose tolerance or impaired fasting glucose
  • Has an HbA1c between 5.7% and 6.4%
  • Has a BMI greater than 35
  • Is younger than 60 years old
  • Is a woman over the age of 60
  • Has had gestational diabetes

However, when looking at individual patients, clinicians must consider thiazolidinediones (TZDs), alpha glucosidase inhibitors, glucagon-like peptide-1 (GLP-1) antagonists, dipeptidyl peptidase-4 (DPP-4) inhibitors and weight loss drugs like orlistat (Xenical, Alli) and phentermine/topiramate (Qsymia).

O’Neal said it is possible to reduce the risk for progression and reduce adverse effects with dual or triple treatment approaches. Some combination therapies include low-dose rosiglitazone (2 mg/day) plus metformin (1000 mg/day) or low-dose pioglitazone (15mg/day) plus metformin (850 mg/day). 

Some clinicians are also using low-dose pioglitazone (15 mg/day) plus metformin (850 mg/day) plus exenatide (10 mcg twice daily).

“While dual/triple therapy options reduce adverse effects, it increases pill burden on the patient. Clinicians and patients must work together to come up with a therapeutic plan that the patient tolerates and accepts while at the same time, takes the patient’s risk profile into consideration to delay the progression to diabetes,” said O’Neal.


  1. O’Neal K, Johnson J. T07 – Pathophysiology of Prediabetes and Early Treatment Considerations. Presented at: AADE 2015; Aug. 5-8, 2015; New Orleans.