Triple therapy in the care of T2DM linked to a decrease in the rate of hepatic steatosis and fibrosis

A recent study compared the effectiveness of triple therapy (metformin / exenatide / pioglitazone) with conventional therapy (metformin / glipizide / insulin glargine) on hepatic fat, hepatic fibrosis and insulin resistance in new patients. diagnosed with type 2 diabetes (T2DM).

Led by Olga Lavrynenko, MD, University of Texas Health Science at San Antonio, the researchers found that patients in the EDICT study treated with triple therapy had less liver steatosis and fibrosis and significantly improved insulin sensitivity compared to conventional treatment, after a period of 6 years.

The study was presented at the 19th annual meeting of the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease.


The history of the EDICT defined the study as an ongoing randomized controlled trial taking place at the Texas Diabetes Institute, aiming to compare 2 therapeutic approaches for the management of patients with recent onset T2DM.

The initial study protocol was designed for a 3-year follow-up and was extended to a 6-year follow-up.

Measurements of FPG, FPI, HbA1c, OGTT, and body fat were measured at baseline and at study end. In addition, liver function tests, AST, ALT, platelets, albumin were obtained in all subjects at baseline and annually for 6 years. Treatment failure was considered if the HbA1c was> 6.5%.

Patients received a transient vibration-controlled elastography (VCTE) measurement at the end of the study to provide a measurement of hepatic fibrosis (LSM) and fatty liver (CAP).

From the LSM value, the severity of fibrosis was classified as


The study included 68 patients who completed the 3-year follow-up and entered the 3-year extension phase. A total of 39 patients were included in the conventional therapy cohort, with a mean age of 52 ± 2 years and a diabetes duration of 4.5 ± 1.1 months. Then, 29 patients were on triple therapy, with a mean age of 50 ± 2 years and a duration of diabetes of 5.4 ± 1.4 months.

The data show that a total of 27 of 39 (69%) subjects receiving conventional treatment had grade 2 or 3 stenosis (S2, n = 9; S3, n = 18), while 9 of 29 (31% ) had it on triple therapy (S2, n = 2; S3, n = 7), all P <.01.>

In addition, 10 out of 39 patients (26%) receiving conventional treatment had grade 3 or 4 fibrosis (F3, n = 7; F4, n = 3), compared to 2 out of 29 (7%) in triple therapy (F3, n = 2), all P = .003.

Lavrynenko and his colleagues noted that triple therapy increased Matsuda insulin sensitivity index scores by 3 times, while conventional therapy had no effect on insulin sensitivity.

The severity of steatosis, measured by CAP (r = 0.42, P <.001 and the severity of fibrosis measured by lsm>P <.001 inversely correlated with the matsuda index of insulin sensitivity. in addition severity steatosis by mri-pdff was resistance>P <.05>

Two key data points showed that hepatic steatosis and fibrosis were inversely correlated with insulin resistance, while anti-diabetic agents that improve insulin resistance reduce liver fat and prevent fibrosis.

Take away food

“T2D subjects treated with triple therapy had less fatty liver and fibrosis and significantly improved insulin sensitivity compared to conventional treatment after 6 years,” the investigators wrote.

“Fatty liver disease, fibrosis, and insulin resistance: implications for therapy”, was published online by WCIRDC.