Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar;33(3):640-648.
doi: 10.1016/j.numecd.2022.12.010. Epub 2022 Dec 21.

Improved glycaemic control in patients with type 2 diabetes has a beneficial impact on NAFLD, independent of change in BMI or glucose lowering agent

Santo Colosimo  1 , Garry D Tan  2 , Maria Letizia Petroni  3 , Giulio Marchesini  3 , Jeremy W Tomlinson  4
Affiliations

Improved glycaemic control in patients with type 2 diabetes has a beneficial impact on NAFLD, independent of change in BMI or glucose lowering agent

Santo Colosimo et al. Nutr Metab Cardiovasc Dis. 2023 Mar.

Abstract

Background and aim: The current focus of the treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) is lifestyle intervention with the aim of significant weight loss alongside aggressive cardiovascular risk reduction. NAFLD is tightly associated with type 2 diabetes (T2D) and obesity. In patients with T2D, glucose lowering agents that promote weight loss have shown a beneficial impact on NAFLD. However, it remains unclear as to whether glucose lowering can improve NALFD in patients with T2D, independent of weight loss.

Methods and results: In a retrospective analysis of data from 637 people with T2D, we examined the longitudinal impact of optimizing glycaemic control with DPP-IV inhibitors, GLP-1RAs and SGLT2 inhibitors on Fatty liver index (FLI) and Fibrosis score 4 (Fib-4) adjusting for changes in BMI and choice of glucose lowering regimen over a 12-month period. Multiple linear regression analysis demonstrated a significant correlation between the change in glycated haemoglobin and change in FLI after adjustment for change in BMI, age, sex, and drug class (R = 0.467, p = 0.031). The greatest reduction in FLI was observed in patients with the largest reduction in glycated haemoglobin (p < 0.0001). The probability of improvements in FLI with optimization of glycaemic control was similar with all 3 glucose lowering agents, despite differences in weight reduction. Similar relationships were observed examining the changes in glycaemic control and Fib-4.

Conclusions: Improvements in glucose control that are independent of weight loss are associated with improvement in NAFLD and should form an integral part of the management patients with co-existent NAFLD and T2D.

Keywords: DPP-IVi; Fatty liver Index; Fib-4; GLP-1RA; Glucose control; NAFLD; SGLT2i; T2DM.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(a) Positive correlation between fatty liver index (FLI) and glycated haemoglobin (corrected for body mass index, BMI) at baseline. The change in both FLI (b) and FIB-4 (d) are associated with the change in glycated haemoglobin after correcting for change in BMI. Correlation between Fi-4 and HbA1c at baseline (c). Grey shaded area is 95% C.I.
Figure 2
Figure 2
The greatest improvement in FLI was observed in the good responders (ΔHbA1c > 11 mmol/mol) compared to the moderate (11 < ΔHbA1c < 0 mmol/mol) and non-responders (ΔHbA1c < 0 mmol/mol) (a–c).
Figure 3
Figure 3
(a) BMI decreased significantly in those patients treated with GLP-1RA and SGLT2i, but not DPP-IVi. (b) Multiple logistic regression demonstrated that the probability of FLI improvement was highest in the good-responders and that this was similar across all 3 classes of glucose lowering agent.
See this image and copyright information in PMC

References

    1. Younossi Z.M., Henry L. Epidemiology of non-alcoholic fatty liver disease and hepatocellular carcinoma. JHEP Rep. 2021;3(4) - PMC - PubMed
    1. Musso G., Cassader M., Rosina F., Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia. 2012;55(4):885–904. - PubMed
    1. Mantovani A., Petracca G., Csermely A., Beatrice G., Targher G. Sodium-glucose cotransporter-2 inhibitors for treatment of nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Metabolites. 2020;11(1) - PMC - PubMed
    1. Newsome P.N., Buchholtz K., Cusi K., Linder M., Okanoue T., Ratziu V., et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384(12):1113–1124. - PubMed
    1. Hartman M.L., Sanyal A.J., Loomba R., Wilson J.M., Nikooienejad A., Bray R., et al. Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes. Diabetes Care. 2020;43(6):1352–1355. - PMC - PubMed

Publication types

MeSH terms