Pharmacogenomics of Type 2 Diabetes Treatment Response
Critical Evidence Gap
The provided evidence does not contain specific pharmacogenomic data linking individual gene variants (with rsIDs) to treatment responses for type 2 diabetes medications. While the evidence discusses genetic associations with diabetes risk (TCF7L2, KCNJ11, PPARG) and mentions that pharmacogenetic research exists for oral antidiabetics, it does not provide the structured variant-level data requested 1, 2, 3.
Available Genetic Information from Evidence
Diabetes Risk Variants (Not Treatment Response)
The evidence identifies genetic variants associated with diabetes susceptibility in Sub-Saharan African populations, but these relate to disease risk rather than drug response:
| Gene | Variant | Population | Association | Evidence Quality |
|---|---|---|---|---|
| TCF7L2 | rs7903146 (T allele) | European & African | Diabetes risk (shared signal) | Replicated, meta-analysis [4] |
| TCF7L2 | rs17746147 | Sub-Saharan African | Diabetes risk (African-specific) | Meta-analysis (n=4347) [4] |
| AGMO | rs73284431 | Sub-Saharan African | Diabetes risk (African-specific novel locus) | Meta-analysis [4] |
| KCNJ11 | Lys23 variant | Multiple populations | Diabetes risk | Replicated [1,3] |
| PPARG | Pro12Ala | Multiple populations | Diabetes risk | Replicated [1,3] |
| ZRANB3 | Not specified | African (AADM cohort) | Diabetes risk (novel African locus) | Single GWAS [4] |
Pharmacogenetic Mentions Without Specific Variants
The research evidence acknowledges that genetic polymorphisms affect treatment response but does not provide the specific rsIDs or detailed response data requested 1, 2, 3:
- Metformin (Biguanides): OCT1 and OCT2 transporter variants mentioned as affecting pharmacokinetics, but no specific rsIDs provided 1, 2
- Sulfonylureas: KCNJ11 (Kir6.2) and ABCC8 (SUR1) variants mentioned for KATP channel function, relevant to neonatal diabetes treatment switching from insulin to oral agents 1, 3
- Thiazolidinediones: PPARG variants mentioned, with hepatosteatosis risk variants noted but not specified 1
- SGLT2 inhibitors: Evidence states data are "just starting to emerge" with no specific variants identified 2
- GLP-1 receptor agonists: No pharmacogenetic data provided in evidence 2
African Population-Specific Considerations
Critical limitation: Most pharmacogenetic studies have been conducted in European populations, with African populations severely underrepresented 4. Key points:
- African populations harbor far greater genetic diversity with ~3 million variants missing from public databases 4
- Africans display lower linkage disequilibrium and shorter haplotype blocks, which aids fine-mapping but requires population-specific studies 4
- African Americans (who comprise most "African" genetic studies) are admixed (~20% European ancestry) and differ environmentally from Sub-Saharan Africans 4
- Only recent initiatives (AADM, DDS, H3Africa) have begun GWAS in Sub-Saharan African populations 4
- No pharmacogenetic treatment response data specific to Sub-Saharan African populations is provided in the evidence
Current Treatment Guidelines (Not Pharmacogenomic)
The evidence emphasizes that current treatment decisions prioritize cardiovascular and renal outcomes over pharmacogenetic considerations 4:
- First-line: Metformin unless contraindicated 4
- Add-on therapy: SGLT2 inhibitors or GLP-1 RAs for patients with established ASCVD, heart failure, or CKD 4, 5
- Insulin: Reserved for severe hyperglycemia (glucose ≥300 mg/dL or A1C ≥10%) or catabolic features 4
- Sulfonylureas: Mentioned as option but with hypoglycemia risk requiring dose reassessment when combined with insulin 4
Recommendation for Obtaining Requested Data
To obtain the structured pharmacogenomic table requested, you would need to access:
- Dedicated pharmacogenomics databases (PharmGKB, CPIC guidelines)
- Systematic reviews specifically focused on pharmacogenetic variants with rsIDs for each drug class
- Population-specific pharmacogenetic studies in African populations (currently very limited) 4
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for diabetes medications
The current evidence base demonstrates that while pharmacogenetic research exists for diabetes medications, comprehensive variant-level data—especially for African populations—remains a critical research gap 4, 1, 2.