What you carry at this position in your DNA and what research says about it.
Type 2 Diabetes Risk: 8/10 evidence, 9 publications.
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Sample genotype (not yours): G/G
Typical Type 2 Diabetes Risk
Standard blood sugar regulation and typical risk of developing type 2 diabetes are expected. Standard response to GLP-1 receptor agonist medications is typical, with a lower likelihood of gastrointestinal side effects.
What this genotype means: Typical blood sugar levels; Standard response to GLP-1 agonists; Lower risk of nausea from liraglutide.
Sample genotype (not yours): A/A
Lowest Type 2 Diabetes Risk
Optimal blood sugar regulation and the lowest risk of type 2 diabetes are associated with this genotype. While highly responsive to DPP-4 inhibitors, there is a significantly increased risk of nausea from GLP-1 agonists.
What this genotype means: Lowest fasting blood glucose; Highly reduced risk of type 2 diabetes; Excellent response to DPP-4 inhibitors.
Sample genotype (not yours): G/A
Lower Type 2 Diabetes Risk
Enhanced insulin sensitivity and lower blood glucose levels contribute to a reduced risk of type 2 diabetes. Response to certain diabetes medications may differ, with a higher chance of mild digestive side effects from GLP-1 agonists.
What this genotype means: Lower fasting blood glucose; Reduced risk of type 2 diabetes; Better response to DPP-4 inhibitors.
Gene function and biological role
Gene Function: The GLP1R gene encodes the glucagon-like peptide-1 receptor, a key player in insulin secretion and blood sugar regulation [1]. When blood sugar rises, GLP-1 hormones bind to this receptor on pancreatic beta cells, triggering insulin release to lower glucose [1]. Beyond the pancreas, this receptor influences appetite, gastric emptying, and cardiovascular health [2]. It is the primary target for modern weight-loss and diabetes medications like semaglutide and liraglutide [3]. Understanding variations in this gene helps predict metabolic health and drug responses.
Variant Impact: A missense mutation in the GLP1R gene, rs3765467, changes the amino acid arginine to glutamine at position 131 of the receptor protein [2]. This structural change alters the receptor's signaling efficiency, making it a gain-of-function variant that produces more cAMP upon activation [2]. Consequently, the altered receptor provides enhanced protection to pancreatic beta cells and improves insulin secretion [2]. This molecular shift directly impacts blood sugar levels, diabetes susceptibility, and how the body responds to various diabetes medications [1].
Key Insight: The minor A allele is a rare gain-of-function variant that makes the GLP-1 receptor more active, protecting pancreatic cells and lowering diabetes risk.
Location: GLP1R. Chromosome 6 · 6p21.2 · 39.1 Mb
Estimated prevalence by population
Global 97.0%; European 99.4%; African 99.5%; East Asian 61.3%; South Asian 82.8%; Americas 93.7%; Ashkenazi 99.5%; Finnish 99.9%; Middle Eastern 98.6%; Amish 90.2%.
Estimated GG genotype frequency.
Global 2.8%; European 0.6%; African 0.5%; East Asian 34.0%; South Asian 16.4%; Americas 6.2%; Ashkenazi 0.5%; Finnish 0.1%; Middle Eastern 1.4%; Amish 9.6%.
Estimated GA genotype frequency.
Global 0.2%; European < 0.1%; African < 0.1%; East Asian 4.7%; South Asian 0.8%; Americas 0.1%; Ashkenazi < 0.1%; Finnish < 0.1%; Middle Eastern < 0.1%; Amish 0.3%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 34594039. Typical Risk.
Blood Glucose. Evidence: 10/10. Source: PMID 29403010. Typical Levels.
Pharmacogenomics
Diabetes Medication Response
DPP-4 Inhibitor Response. Evidence: 6/10. Source: PMID 27858848. Typical Response.
GLP-1 Agonist Response. Evidence: 5/10. Source: PMID 35034150. Stronger Response.
Showing effects for A/A genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 34594039. Lowest Risk.
Blood Glucose. Evidence: 10/10. Source: PMID 29403010. Lowest Levels.
DPP-4 Inhibitor Response. Evidence: 6/10. Source: PMID 27858848. Stronger Response.
GLP-1 Agonist Response. Evidence: 5/10. Source: PMID 35034150. Higher Side Effects.
Showing effects for G/A genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 34594039. Lower Risk.
Blood Glucose. Evidence: 10/10. Source: PMID 29403010. Lower Levels.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Standard GLP-1 receptor function maintains typical blood glucose levels and metabolic health [1]. Pancreatic beta cells secrete insulin normally in response to blood sugar rises [1]. Clinical studies show that glucose levels remain within the expected average range for the general population [1]. When treated with GLP-1 receptor agonists like liraglutide, standard therapeutic benefits are achieved with a lower risk of nausea or vomiting [2]. Response to DPP-4 inhibitors like sitagliptin is typical and may not be as pronounced as in carriers of the minor allele [3]. Lifestyle factors such as diet and exercise play the primary role in determining overall metabolic outcomes.
Typical blood sugar levels; Standard response to GLP-1 agonists; Lower risk of nausea from liraglutide.
Sample genotype: AA (Homozygous)
Inheriting two copies of the protective A allele maximizes the signaling efficiency of the GLP-1 receptor [1]. This genetic profile is strongly associated with the lowest fasting blood glucose levels and a highly reduced risk of type 2 diabetes [2]. Pancreatic beta-cell function is better preserved over time, supporting long-term metabolic health [1]. If diabetes treatment is ever required, DPP-4 inhibitors like sitagliptin show exceptional efficacy [3]. However, GLP-1 receptor agonists like liraglutide are much more likely to cause gastrointestinal side effects, including nausea and vomiting [4]. These side effects are linked to the heightened sensitivity of the altered receptors in the digestive tract. These insights allow for highly personalized approaches to metabolic wellness and medical treatment.
Lowest fasting blood glucose; Highly reduced risk of type 2 diabetes; Excellent response to DPP-4 inhibitors.
Sample genotype: GA (Heterozygous)
Possessing one copy of the protective A allele alters the GLP-1 receptor structure, enhancing its signaling efficiency [1]. This gain-of-function change leads to lower fasting blood glucose levels and a reduced risk of developing type 2 diabetes [2]. Pancreatic beta cells are better protected from stress, helping to preserve insulin-producing capacity over time [1]. When managing diabetes, there is an increased likelihood of a highly favorable response to DPP-4 inhibitors like sitagliptin [3]. Conversely, treatment with GLP-1 receptor agonists like liraglutide may trigger more frequent gastrointestinal side effects, such as nausea or diarrhea [4]. These side effects are often mild but can influence how well a medication is tolerated. Monitoring metabolic markers and discussing medication options with a healthcare provider can help optimize treatment plans.
Lower fasting blood glucose; Reduced risk of type 2 diabetes; Better response to DPP-4 inhibitors.
Variants with shared genetic architecture
rs10305420 · GLP1R Gene · Chr 6 · Type 2 Diabetes Risk
rs6923761 · GLP1R Gene · Chr 6 · GLP-1 Medication Response
rs10830963 · MTNR1B Gene · Chr 11 · Type 2 Diabetes Risk
A cross-population atlas of genetic associations for 220 human phenotypes.
Content updated August 2026.
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