Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: A randomised double-blind placebo-controlled study

Abstract

Aims/hypothesis Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. Methods Seventy-one patients (age 18-70 years), who did not reach HbA 1c 6.5% (48 mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16 week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0 mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16 weeks after randomisation (allocation by central office) to Alo (n=25), Alo/Pio (n=22) or Pbo (n=24). Blood was sampled at prespecified intervals, starting at 15 min before and ending 8 h after meal ingestion. Results At week 16, Alo (n=25) and Alo/Pio (n=21) vs Pbo (n=24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p<0.001), as well as in chylomicron TG (p<0.001) and VLDL1 TG iAUCs (p<0.001 and p=0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p=0.028), and a non-significant trend towards a decrease with Alo/Pio (p=0.213). The incidence of adverse events was low and consistent with previous studies. Conclusions/interpretation Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TGrich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells. Trial registration: ClinicalTrials.gov number NCT00655863. Funding: The study was funded by Takeda Global Research &Development. © 2012 Springer-Verlag.