Exenatide induces an enhanced endogenous glucagon-like peptide-1 secretory response in patients receiving basal insulin.

CONTEXT: Prolonged exposure to hormonal therapy can affect endogenous hormone secretion. In type 2 diabetes (T2DM), glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly being administered in combination with therapies targeting additional hormones (including glucose-dependent insulinotropic polypeptide [GIP], glucagon, and insulin). However, little is known on how they affect endogenous GLP-1 secretion.

OBJECTIVE

We sought to evaluate the effect of exenatide b.i.d on endogenous secretion of GLP-1, GIP, and glucagon in patients treated concurrently with basal insulin.

DESIGN/SETTING/PATIENTS: In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).

OUTCOME: Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.

RESULTS

There were no differences between groups in response profiles of glucagon and GIP. While there were no differences in fasting GLP-1, Glar/Exe induced higher GLP-1 concentrations than the other treatments at 30 and 60 minutes post-challenge at 8 weeks (both P < .05). On the 8-week OGTT, baseline-adjusted GLP-1 was the highest in Glar/Exe at each of 30 minutes (P = .037), 60 minutes (P = .007), and 90 minutes (P = .039). Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar/Exe (P = .037).

CONCLUSION

When combined with basal insulin therapy, exenatide induces an enhanced post-challenge endogenous GLP-1 secretory response following its cessation, with no differential effect on glucagon and GIP secretion.