Improved HbA1c in Adults with T2D Had Beneficial Impact on NAFLD, According to New Study

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Adults with type 2 diabetes (T2D) may be able to reduce their liver fat and improve their liver fibrosis stage with reductions in HbA1c, according to a retrospective analysis published in Nutrition, Metabolism, & Cardiovascular Diseases.

In a post-hoc analysis of clinical data from adults with T2D treated with an SGLT-2 inhibitor (SGLT2i), GLP-1 receptor agonist (GLP1RA), or DPP-IV inhibitor (DPP-IVi) to improve glycemic control, reducing HbA1c was associated with improvements in fatty liver index (FLI) and fibrosis-4 score (FIB-4), regardless of which glucose-lowering agent was used or body mass index (BMI) at baseline.

“There is a lack of data demonstrating the longitudinal impact of improved glucose control (in isolation) on nonalcoholic fatty liver disease (NAFLD) in patients with T2D,” wrote lead author Jeremy Tomlinson, MD, PhD, professor of metabolic endocrinology, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, United Kingdom, and colleagues.

To determine whether glucose lowering can improve NAFLD in patients with T2D, independent of weight loss, Tomlinson and colleagues conducted a retrospective study of clinical records from 637 adults with T2D (60% men; mean age, 61.6 years) attending a clinic in Italy who were prescribed a GLP-1RA, SGLT-2i, or DPP-IVi from 2014 to 2017.

Over a 12-month period, liver ultrasounds were performed routinely for all participants, and FLI and FIB-4 were calculated as surrogate markers of fatty liver and fibrosis, respectively. Participants with a ≥1% HbA1c reduction were deemed “good glycemic responders” to therapy, those with an HbA1c reduction of 0.1% to 0.9% were “moderate glycemic responders,” and those with no change or an increase in HbA1c were defined as “glycemic nonresponders.”

Among the total cohort, 44% fell into the “good glycemic responders”group, 36% into the “moderate glycemic responders” group, and 20% into the “glycemic nonresponders” group at baseline, according to researchers.

After 1 year of treatment with GLP-1RA, SGLT-2i, or DPP-IVi, good glycemic responders had a HbA1c reduction from 8.9% to 6.86%, moderate glycemic responders had a reduction from 7.89% to 7.39%, and glycemic nonresponders had an increase from 7.59% to 8.23%. BMI significantly decreased in all groups compared to baseline, with the greatest reduction observed in the “good glycemic responders” cohort. Waist circumference also significantly decreased in all groups.

Investigators noted total cholesterol was significantly decreased in good glycemic responders and moderate glycemic responders and alanine transaminase (ALT) decreased only in good glycemic responders.

At baseline, prior to new drug initiation, FLI correlated with HbA1c, even after adjusting for BMI (r=0.736, P=.001). After adjusting for change in BMI, age, class of drug, baseline HbA1c, and baseline FLI, investigators observed a positive correlation between change in HbA1c and change in FLI class at 1 year (r=0.706, P<.001). The greatest reduction in FLI was seen in participants with the largest reduction in HbA1c (P<.0001).

At baseline, no association was observed between HbA1c and FIB-4, however, at 1 year, Tomlinson and colleagues observed a positive correlation between change in HbA1c and Fib-4 after adjusting for change in BMI, sex, age, drug classes, and FIB-4 at baseline (r=0.666, P=.001). Good glycemic responders had the greatest reduction in FIB- 4 from baseline to 1 year, according to the results.

“Whilst weight loss must be the key priority in treating patients with NAFLD, these data suggest that optimization of glycemic control independently of weight should be an important part of the management of patients with NAFLD,” concluded Tomlinson et al. “However, they do not replace the need for prospective, well-designed, randomized controlled studies to specifically address the quantitative impact of optimization of glucose control in patients with NAFLD.”

Reference: Tomlinson JW, Colosimo S, Tan GD, Petroni ML, Marchesini G. Improved glycemic control in patients with type 2 diabetes has a beneficial impact on NAFLD, independent of change in BMI or glucose lowering agent. Nutr Metab Cardiovasc Dis. 2022. doi:10.1016/j.numecd.2022.12.010.