Treatment based on physiologic assessment may help prevent diabetes

In a retrospective observational study, patients with prediabetes were assigned to a risk category for diabetes based on presence and severity of insulin resistance, impaired beta-cell function, and hyperglycemia, then treated accordingly.


Patients with prediabetes may benefit from treatment based on physiologic assessment of insulin resistance and other factors, according to recent research.

Researchers performed a retrospective observational study of patients with increased risk for type 2 diabetes at a community practice in southern California. All patients received an oral glucose tolerance test and were assigned a risk category based on the presence and severity of insulin resistance, impaired beta-cell function, and hyperglycemia (defined as a one-hour plasma glucose concentration above 8.6 mmol/L [155 mg/dL]). Patients considered at high risk for type 2 diabetes were recommended to receive metformin, pioglitazone, a glucagon-like peptide-1 (GLP-1) receptor antagonist, and lifestyle therapy. Metformin, pioglitazone, and lifestyle therapy were recommended for those considered at intermediate risk. Patients in the high-risk and intermediate-risk categories who declined to take the medications were assigned to the lifestyle therapy alone and served as the comparison group. Patients found to have low risk were not included.

Follow-up visits took place every six months. Oral glucose tolerance tests were done at six months, then every two years, or sooner if patients had HbA1c levels above 6.0% or fasting plasma glucose levels above 6.11 mmol/L (110 mg/dL). The study's primary outcome was incidence of type 2 diabetes as defined by American Diabetes Association criteria during the study period. Results were published by The Lancet Diabetes & Endocrinology on Sept. 14.

From Jan. 1, 2009, through Dec. 31, 2016, 1,769 patients were evaluated for study inclusion, and 747 (42%) were categorized as being at high or intermediate risk. Four hundred twenty-two patients were stratified into a treatment group and completed adequate follow-up. Of these, 141 received the recommended intermediate-risk therapies, 81 received the high-risk therapies, and 200 (76 high risk and 124 intermediate risk) received lifestyle therapy alone. During a mean follow-up of 32 months, 28 patients progressed to diabetes. Compared to lifestyle therapy alone, the adjusted hazard ratio for progression to type 2 diabetes was 0.29 (95% CI, 0.11 to 0.78; P=0.0009) in patients taking metformin and pioglitazone (the intermediate-risk group) and 0.12 (95% CI, 0.02 to 0.94; P=0.04) in patients taking metformin, pioglitazone, and GLP-1 receptor agonists (the high-risk group). Among the variables assessed, change in beta-cell function appeared to be the strongest predictor of progression to type 2 diabetes.

The authors noted that their study was retrospective and observational, that the real-world data were derived from a single practice, that medication costs may be an issue, and that it is uncertain whether their findings indicate prevention or masking of diabetes, among other limitations. However, they concluded that targeted therapy aimed at correcting pathophysiologic abnormalities in high-risk patients appears to substantially decrease development of type 2 diabetes. They called for larger, longer, multicenter studies to help confirm their results.

An accompanying comment pointed out that the authors' approach to type 2 diabetes prevention was logical, since evidence indicates that 80% of beta-cell function is typically already lost by the time the disease is diagnosed. “Many would consider intervention with three pharmaceutical agents, one of which is an injectable, to be excessive in this population,” the comment author wrote. “However, the complications of type 2 diabetes can be devastating and anything that can be done to avoid diabetes and therefore its complications is worthy of consideration.”