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OBJECTIVE: A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy. RESEARCH DESIGN AND METHODS: We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study;n= 254), with replication for routinely available markers in U.K. electronic health care records (Clinical Practice Research Datalink [CPRD];n= 23,001). In CPRD, we evaluated associations between baseline markers and 3-year durability of response. To test the specificity of findings, we repeated analyses for glucagon-like peptide 1 (GLP-1) receptor agonists (PRIBA,n= 339; CPRD,n= 4,464). RESULTS: In PRIBA, markers of higher insulin resistance (higher fasting C-peptide [P= 0.03], HOMA2 insulin resistance [P= 0.01], and triglycerides [P< 0.01]) were associated with reduced 6-month HbA1cresponse to DPP-4 inhibitors. In CPRD, higher triglycerides and BMI were associated with reduced HbA1cresponse (bothP< 0.01). A subgroup defined by obesity (BMI ≥30 kg/m2) and high triglycerides (≥2.3 mmol/L) had reduced 6-month response in both data sets (PRIBA HbA1creduction, 5.3 [95% CI 1.8, 8.6] mmol/mol [0.5%] [obese and high triglycerides] vs. 11.3 [8.4, 14.1] mmol/mol [1.0%] [nonobese and normal triglycerides];P= 0.01). In CPRD, the obese, high triglycerides subgroup also had less durable response (hazard ratio 1.28 [1.16, 1.41];P< 0.001). There was no association between markers of insulin resistance and response to GLP-1 receptor agonists. CONCLUSIONS: Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP-4 inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP-4 inhibitor therapy.

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Journal article


Diabetes Care

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