Researchers Identify Clinical Factors That Predict Response to Glucose-Lowering Therapies

April 17, 2021
Larry Hanover

The authors said their work is an effort towards making more tailored therapy a reality.

Knowing the collective clinical factors that determine patient response can be used to predict response to glucose-lowering medication used in the treatment of type 2 diabetes (T2D), a new study found.

The combination of disease duration/age at diagnosis and glycated hemoglobin A1C (HbA1c)/serum C-peptide reactivity (CPR) ratios is a collective risk factor predicting response to diabetes medications, according to a study by researchers in Japan published in the Journal of Diabetes Investigation.

Despite greater understanding of T2D and the availability of new medications and technologies, only about half of American adults with the disease achieve control of their blood sugar levels, as measured by the percentage achieving an HbA1c level of 53 mmol/mol (7.0%), according to results from the National Health and Nutrition Survey.

In the current study, researchers wanted to create a model to predict which patients are most likely to respond to diabetes medications. The work, part of the Japan Diabetes Clinical Data Management Study Group, involved a nationwide database to involving multiple institutions across Japan. Data from 7009 patients from 2005 to 2018 met criteria for the study, which sought patients meeting criteria for severe T2D.

The study evaluated factors most likely to predict insulin treatment. It then looked to compare changes in HbA1c levels during the 6 months from the start of glucose-lowering medication and prescription content at month 6 between patients who appeared to be more severe and those who were mild.

Patients in the study were on an oral antidiabetic drug, insulin, and/or glucagon-like peptide 1 receptor agonist. One portion of the study determined that age at diagnosis, disease duration, and HbA1c level at the start of medication were associated with the probability of receiving insulin treatment, but age at the start of medication, sex, and BP were slightly associated, and BMI was not. Further analysis showed that 1/age at diagnosis, disease duration, and HbA1c levels predicted insulin treatment positivity.

A second portion of the study determined that age at diagnosis, disease duration, HbA1c level, and CPR levels were associated with the probability of receiving insulin treatment. Furthermore, these factors and 1/serum CPR predicted insulin positivity in patients. In the area-under-curve analysis, area increased for the disease duration/age at diagnosis ratio and HbA1c/serum CPR ratio.

An index was then constructed for each part of the study. In the first study, for the upper third, age at diagnosis was much lower, disease duration was far longer, and HbA1c levels were higher. For the second study, the criteria were similar except that CPR was considered; it was markedly lower in the upper third.

More patients with higher indices had higher HbA1c levels during glucose-lowering medication even though many more were on insulin than those with lower indices. In fact, many in the upper third did not achieve target HbA1c levels even though more than 4 times as many patients received insulin as those in the lower third.

The authors said greater understanding of obesity’s relationship to T2D would further help determine which patients would respond to glucose-lowering medication and make tailored therapy a reality. Although those with hypertension are nearly 2.5 times as likely to develop T2D, age at diagnosis might affect disease severity more than BP and BMI.

Those with early onset T2D diagnosed younger than age 40 showed significantly worse glycemic control than those diagnosed above 40 across all lengths of diabetes duration. Furthermore, those between 15 and 30 were more likely to be treated with insulin than those between 40 and 50.

However, poor glycemic control is related to other factors, including the disease process itself, inadequacy of therapeutic regiments, and physician and patient attitudes, the authors said.


Kanatsuka A, Sato Y, Higashi Y, et al. The combination of disease duration to age at diagnosis and hemoglobin a1c to serum c‐peptide reactivity ratios predicts patient response to glucose‐lowering medication in type 2 diabetes: A retrospective cohort study across Japan (JDDM59). J Diabetes Investig. Published online April 10, 2021. doi:10.1111/jdi.13558