The GLP-1 analogue liraglutide improves first-phase insulin secretion and maximal beta-cell secretory capacity over 14 weeks of therapy in subjects with Type 2 diabetes

Aims: We investigated the clinical effect of liraglutide, a long- acting GLP-1 analogue, on insulin secretion in Type 2 diabetes. Methods: Thirty-nine subjects (28 completed) from a randomised trial received a hyperglycaemic clamp (20 mM) with intravenous arginine stimulation, and an insulin modified frequently sampled intravenous glucose tolerance test (FSIGTT), to test maximal- and first-phase insulin secretion, respectively, before and after 14 weeks’ liraglutide (0.65, 1.25 or 1.9 mg/day) or placebo treatment. Twelve healthy, untreated matched subjects were also tested. Results: Compared with placebo, the 1.25 and 1.9 mg/day doses of liraglutide increased maximal beta-cell secretory capacity with 6.3 pM (95% CI: 2.9–9.6) B114%, and 7.2 pM (95% CI: 3.3–11.0)
B97%, respectively. These doses also increased first-phase insulin secretion relative to placebo by 11.0 pMh (95% CI: 6.6–15.4) B124% and 9.5 pMh (95% CI: 3.5–15.5) B107%, respectively. 1.25 mg/day liraglutide significantly increased second-phase insulin secretion (Po0.01). There was no effect on glucose effectiveness or insulin sensitivity (minimal model). Insulin secretion was greater
(except second-phase secretion) in the control group. Conclusion: In subjects with Type 2 diabetes, 14 weeks’ once-daily liraglutide (1.25 and 1.9 mg/day) markedly improves beta-cell function, significantly increases first-phase insulin secretion and maximal beta-cell secretory capacity.