Genetics
CETP TaqIB genotype shows no association with the effect of dulaglutide on HbA1c or hepatic steatosis, unlike PNPLA3 (Endocrine 2024)
Original title: The effect of dulaglutide on glycated hemoglobin is associated with PNPLA3 Ι148Μ gene polymorphism in patients with type 2 diabetes mellitus
This retrospective study evaluated the effect of 6 months of weekly dulaglutide 1.5 mg on glycated hemoglobin (HbA1c) and non-invasive hepatic steatosis indices across genotypes of PNPLA3 I148M (rs738409) and CETP TaqIB (rs708272) in 80 patients with type 2 diabetes and NAFLD. HbA1c, fatty liver index, and hepatic steatosis index all significantly decreased after treatment. Homozygotes for the reference PNPLA3 allele (CC) showed a 2.4-fold greater HbA1c decrease and heterozygotes (CG) a 1.6-fold greater decrease than GG homozygotes, an effect largely limited to female patients, though this pattern was not seen for the hepatic steatosis indices. No association was observed between the CETP rs708272 genotype and any of the parameters studied. The authors conclude that PNPLA3, but not CETP, was associated with the effect of dulaglutide on HbA1c, with sex-specific effects also noted.
Original abstract
Purpose: The evaluation of the effect of dulaglutide on glycated hemoglobin (HbA1c) and non-invasive indices of hepatic steatosis among different genotypes of the PNPLA3 I148M (rs738409) and CETP Taq1B (rs708272) polymorphisms in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).
Methods: Relevant data from patients with inadequately controlled T2DM, also displaying NAFLD, administered 1.5 mg dulaglutide weekly for 6 months were retrospectively retrieved. The non-invasive indices, fatty liver index (FLI) and hepatic steatosis index (HSI), were calculated. Genotyping for rs738409 and rs708272 were performed with polymerase chain reaction.
Results: Data from 80 patients (39 females), aged 64.4 ± 9.5 years and displaying a baseline BMI of 34.5 ± 5.8 kg/m2, were retrieved at baseline and after 6 months (endpoint) of dulaglutide treatment. Glycated hemoglobin (HbA1c; -0.72 ± 1.10%; p < 0.001), FLI (-5.8 ± 9.8; p < 0.001) and HSI (-1.18 ± 3.51; p = 0.004) significantly decreased after treatment. Lipid profile and liver function tests also improved after treatment. Overall, homozygotes for the reference rs738409 allele (CC) displayed a 2.4-fold decrease (p = 0.002) and heterozygotes (CG) an 1.6-fold decrease (p = 0.013) compared to GG homozygotes after treatment, but the effect was largely limited to female patients. No similar effect was observed in FLI, HSI and other relevant parameters. No association was observed between rs708272 and any of the parameters studied.
Conclusions: rs738409, but not rs708272, was associated with the effect of dulaglutide on HbA1c, but not on presumed hepatic steatosis or other relevant parameters. Sex-specific effects were also noticed.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.