Impact of insulin glargine and lixisenatide on β-cell function in patients with type 2 diabetes mellitus: A randomized open-label study.

It is known that β-cell function can be enhanced by direct stimulation of insulin secretion or by induction of β-cell rest, but whether both strategies can complement each other has not yet been examined. A total of 28 people with type 2 diabetes (glycated haemoglobin 7.8% ± 0.5%) were treated with either lixisenatide or titrated insulin glargine, followed by their combined administration, each over 4 weeks. First- and second-phase insulin secretion during an intravenous glucose challenge were calculated. First- and second-phase insulin secretion were not increased with glargine alone, but increased after addition of lixisenatide ( P  < .001). Lixisenatide alone increased first- and second-phase insulin secretion ( P  < .01). Addition of insulin glargine tended to further increase first-phase insulin secretion (P = .054), as well as insulin and C-peptide concentrations ( P  < .05). Second-phase insulin secretion was not affected by the addition of glargine. The sequence of initiating lixisenatide or glargine had no effect on the final measures of glycaemia or insulin secretion. Thus, lixisenatide and, to a lesser extent, insulin glargine, increase glucose-stimulated insulin secretion in an additive manner.