# Genetic variants associated with glycemic and weight loss response to vildagliptin as add-on therapy to metformin in Egyptian obese type 2 diabetic patients: potential consequences on cardiac risk factors

## TL;DR

This study finds that genetic variants in certain genes influence how well Egyptian obese type 2 diabetic patients respond to vildagliptin and metformin treatment in terms of blood sugar and weight loss.

## Contribution

The study identifies specific genetic variants linked to treatment response and their impact on cardiac risk factors in a specific population.

## Key findings

- The GG genotype of DPP4, GLP1R, and KATP genes is associated with better glycemic response to vildagliptin and metformin.
- The AA genotype of GLP1R is associated with better weight loss response.
- Lower baseline weight and BMI correlate with better treatment outcomes, while gender does not affect response.

## Abstract

This study aims to identify the genetic and clinical characteristics that affect the glycemic and weight loss responses to vildagliptin (Vilda) plus metformin (Met) among Egyptian obese type 2 diabetic (T2DM) patients. Furthermore, these responses were linked to homocysteine (Hcy) level as another cardiovascular risk factor.

One hundred twenty-six obese newly diagnosed T2DM Egyptian patients (38.9% male and 61.1% female) fulfilling the inclusion criteria and signing the consent form were treated with Met plus Vilda for 12 months and genotyped for rs6741949 in the DPP4, rs6923761 in the GLP1R, and rs2285676 in the KATP (KCNJ11) genes. At 12 months post-treatment, the glycemic and weight loss-responses were defined as a reduction of the baseline HbA1c by more than 1% and a reduction of the baseline weight by more than 3% respectively.

The GG genotype of the DPP4, GLP1R, and KATP had the significant highest distribution and glycemic response to Vilda/Met than other genotypes [odds ratio (OR) = 3.55, 8.56 & 4.89; 95% confidence interval (CI) 1.13–9.51, 1.32–92.4 & 1.2–22.2; p = 0.033, 0.021 & 0.03, respectively]. However, the AA genotype of rs6923761 in the GLP1R had a significantly higher weight loss response than GA and GG genotypes (OR = 0.39 & 0.17; 95% CI 0.65–0.44 & 0.22–0.67, p = 0.84). Further analysis showed that lower baseline weight and BMI were associated with better glycemic and weight loss responses to Vilda/Met, while gender had no effect. Of note, glycemic and body weight loss responders show a higher reduction in Hcy level than non-responders.

Glycemic control and body weight loss, and hence amelioration of Hcy level by Vilda as add-on therapy to Met in Egyptian T2DM obese patients are subjected to genetic variation in one or more of the DPP-4, GLP1R and KATP genes involved in Vilda's modes of action. The GG genotype for the three genes is associated with better glycemic response; however, the AA genotype of GLP1R is associated with better weight loss response. Gender has no effect; however, lower initialbody weight results in better glycemic and weight loss response.