Glp1r, the glucagon-like peptide-1 receptor, is a key component in glucose metabolism regulation. It is activated by glucagon-like peptide-1 (GLP-1), a peptide hormone released from intestinal L cells after nutrient intake. Activation of Glp1r potentiates glucose-induced insulin secretion from pancreatic beta cells, inhibits beta-cell apoptosis, promotes beta-cell neogenesis, reduces glucagon secretion, delays gastric emptying, promotes satiety and increases peripheral glucose disposal [2]. These functions link nutrient consumption with blood sugar control, making Glp1r crucial for maintaining metabolic homeostasis.

Polymorphisms in the Glp1r gene are associated with type 2 diabetes. For example, in a study, the G-risk allele at rs761387 was associated with higher total GLP-1, active GLP-1 and a trend toward higher glucose during an oral glucose tolerance test (OGTT), while during a glipizide challenge, it was associated with higher insulin levels. However, other tested variants were not associated with the outcomes. This indicates that Glp1r variation affects GLP-1 levels and incretin signaling, potentially influencing type 2 diabetes risk [1]. Also, in overweight Chinese type 2 diabetes patients, the variant allele T of rs10305420 was associated with less weight loss and lower HbA1c reduction after 6-month exenatide treatment, suggesting its potential as a biomarker for precision medicine in this patient group [3].

In conclusion, Glp1r plays a vital role in glucose metabolism and energy balance. Genetic variations in Glp1r are associated with type 2 diabetes and response to anti-diabetic drugs, highlighting its significance in understanding the pathogenesis of type 2 diabetes and developing personalized treatment strategies.