Among a cohort of patients with type 2 diabetes, those with markers for higher insulin resistance responded poorly to DPP-IV inhibitor therapy compared with those with less insulin resistance, according to researchers in the United Kingdom.
“We currently have a wide choice of glucose-lowering treatments for type 2 diabetes,” John Dennis, a PhD student at the University of Exeter Medical School, told Endocrine Today. “While most guidelines agree that metformin is the optimum first-line treatment, after that there is no clear ‘best treatment,’ with choice left open to the clinician and mainly guided by cost and side-effect profile.”
Dennis and colleagues conducted a prospective study of patients with type 2 diabetes who were not being treated with insulin to assess the relationship of insulin resistance and insulin secretion with 6-month glycemic response to DPP-IV inhibitors (n = 254). The researchers also used electronic medical records (n = 23,001) to evaluate possible links between patients’ markers at baseline and 3-year response, and tested the specificity of their results by repeating the analysis with GLP-1 receptor agonists.
Several markers of higher insulin resistance were associated with a reduced 6-month HbA1c response to DPP-IV inhibitors, the researchers reported, including higher fasting C-peptide (P = .03), HOMA2 insulin resistance (P = .01) and triglycerides (P < .01).
In the review of medical records, Dennis and colleagues wrote that higher BMI and higher levels of triglycerides were both associated with response to DPP-IV inhibitors (P < .01 for both).
In the prospective study, patients with high triglycerides and obesity had a reduced 6-month response compared with those without obesity and normal triglycerides (5.3 mmol/mol; 95% CI, 1.8-8.6 vs. 11.3 mmol/mol; 95% CI, 8.4-14.1), the researchers wrote. The review of patient records also showed a less durable response in patients with obesity and high triglycerides (HR = 1.28; 95% CI, 1.16-1.41).
Dennis and colleagues reported that markers of insulin resistance were not associated with response to GLP-1 receptor agonists.
“While there is a lot of excitement about the potential of precision medicine to improve treatment, relatively few robust predictors of response to glucose-lowering treatment have been identified. Our study is the first to robustly identify simple markers associated with response to DPP-IV inhibitor therapy,” Dennis said. “The next step is to replicate these findings in data from existing trials of DPP-IV inhibitors and look at predictors of response for other type 2 diabetes drugs, both of which are ongoing.”
– by Andy Polhamus
Dennis reports no relevant financial disclosures. Please see the study for a list of all other authors’ relevant financial disclosures.