Background and Objectives: Personalized management of diabetes has become an imperative
since majority of monotherapy fails within 3 years of its use. Identifying responders from nonresponders
for a certain type of therapy would reduce a period of unsuccessful treatment and minimize
health care costs. Incretin therapies, mainly glucagon-like peptide (GLP)-1 receptor agonists (GLP-
1RA) are relatively new glucose-lowering agents which increase insulin and lower glucagon response
as well as slow down glucose absorption by acting on gastric emptying. However, problem with incretin-
based therapy is distinguishing responders from non-responders and currently lack of specific
predictors of treatment response.
Discussion: Experimental data demonstrated that activation of GLP-1 and gastrin signaling induces
beta cell neogenesis, leading to glucose-dependent insulin secretion. Several studies demonstrated
better glycemic control in patients with type 2 diabetes (DMT2) co-treated with proton pump inhibitors
(PPI) and incretin based therapy agents.
Conclusion: Higher gastrin levels in patients with diabetes prior to initiation of treatment with incretin
mimetics could suggest a better potential for reversible human β-cell reprogramming with concomitant
incretin therapy. Therefore, baseline levels of endogenous gastrin could be used as a predictor of response
to GLP-1 therapy. In addition, treatment with PPI could also raise gastrin levels and in patients
treated with GLP-1RA, lead to better glycemic control by initiating β-cell neogenesis and proliferation
of pancreatic β-cells.