SGLT2i and GLP-1RA May Improve Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus

Investigators examined the safety and efficacy of SGLT2i and GLP-1RA on treatment of nonalcoholic fatty liver disease in type 2 diabetes mellitus.

The following article is a part of conference coverage from the Digestive Disease Week 2021 Annual Meeting , held virtually from May 21 to 23, 2021. The team at Gastroenterology Advisor will be reporting on the latest news and research conducted by leading experts in gastroenterology. Check back for more from DDW 2021.


Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) may improve hepatic steatosis in patients with concomitant type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), according to study results presented at Digestive Disease Week 2021.

NAFLD is commonly associated with T2DM. Previous studies have shown improvement in NAFLD when SGLT2i or GLP-1RA were utilized. However, evidence is currently limited on their safety and efficacy. Based on the aforementioned knowledge gaps, investigators aimed to examine existing evidence on the efficacy of SGLT2i and GLP-1RA on treatment of NAFLD in T2DM.

Researchers searched 3 electronic databases until June 21, 2020. The investigators pooled continuous outcomes by utilizing the standardized mean differences (SMD) with STATA 16.1. They determined dichotomous outcomes by risk ratio (RR) via RevMan 5.3. A total of 18 articles which involved 2009 participants were included in the meta-analysis.

The study consisted of 669 patients on GLP-1RA, 260 on SGLT2i, 188 on metformin, 152 on insulin-based therapies (consisting of insulin and insulin secretagogues), 136 on incretin-based therapies, 87 on thiazolidinediones (TZD), 15 on a combination of metformin and TZD, and 502 on conventional drugs.

Hepatic fat content was measured utilizing magnetic resonance imaging proton density fat fraction (MRI-PDFF), ultrasonography, liver to spleen (L/S) attenuation ratios examined via computed tomography (CT) scans, controlled attenuation parameter (CAP) scores, and Hepatic Steatosis Index (HSI).

According to investigators, GLP-1RA treatment significantly reduced hepatic fat content post-treatment (SMD, -1.065; 95% CI, -1.643 to -0.488; P <.001), when compared with controls (SMD, -0.548; 95% CI, -0.799 to -0.298; P <.001), metformin (SMD, -0.639; 95% CI, -1.167 to -0.111; P =.018), and insulin-based therapies (SMD, -0.674; 95% CI, -0.977 to -0.370; P <.001).

SGLT2i treatment significantly reduced hepatic fat content, as measured by MRI-PDFF (SMD, -0.789; 95% CI, -1.404 to -0.175; P =.012) and when compared with controls (SMD, -0.923; 95 % CI, -1.562 to -0.285; P =.005). SGLT2i treatment significantly improved L/S attenuation ratios (SMD, 0.456; 95% CI, 0.142 to 0.771; P =.004). This improvement was greater compared with insulin-based therapies (SMD, 0.614; 95% CI, 0.116 to 1.112; P =.016) and metformin (SMD, 1.957; 95% CI, 1.105 to 2.809; P <.001).

Compared with controls, SGLT2i treatment had a greater reduction in CAP scores (SMD, -1.376; 95% CI, -2.540 to -0.213; P =.02).

The study authors concluded that both GLP-1RA and SGLT2i show promise for the improvement of hepatic steatosis in patients with concomitant T2DM and NAFLD. However, further long-term studies are needed to assess the effects of GLP-1RA and SGLT2i on NAFLD in patients with T2DM.

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Wong C, Yaow CYL, Lee MH, et al. A meta-analysis of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Poster presented at: Digestive Disease Week Annual Meeting; May 21-23, 2021. Abstract Sa375.