Gastric Emptying Delay with Pre-Meal Administration of Metformin and Anagliptin in Type 2 Diabetes: Effects on Postprandial Glucose and Triglyceride Levels in a Two-Case Report

BACKGROUND Metformin is a treatment for type 2 diabetes and has been reported to reduce plasma triglyceride levels in addition to plasma glucose levels. We recently reported that the administration of metformin before fat loading reduces the postprandial triglyceride concentration and slows gastric emptying in an animal model. We confirmed that pre-meal administration of metformin reduces the postprandial triglyceride concentration in the pilot clinical study. Metformin is known to increase glucagon-like peptide-1 (GLP-1) secretion, and we hypothesized that its combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor, which prevents the inactivation of GLP-1 in the blood, would enhance the delayed effect of gastric peristaltic emptying. To prove this hypothesis, we initiated a clinical trial to examine the effects of pre- and post-meal administration of a combination tablet of metformin and anagliptin, a DPP-4 inhibitor, on glucose and lipid metabolism and gastric emptying measured using 13C-acetate (jRCTs051200098). However, because the trial had to be terminated due to the COVID-19 pandemic, we report the details of the 2 patients for whom data were obtained. CASE REPORT Both cases showed that pre-meal administration of metformin and anagliptin reduced the postprandial triglyceride concentrations and increased active GLP-1 levels, compared with post-meal administration. In addition, gastric emptying was delayed with pre-meal administration of metformin and anagliptin. CONCLUSIONS Pre-meal administration of metformin and anagliptin reduced postprandial glucose and triglyceride concentrations, potentially through a delay in gastric emptying. Thus, changing the timing of medication may improve their therapeutic effects.