An analysis of patient data from the EDICT study demonstrates the potential benefit of triple therapy in patients with new-onset type 2 diabetes.
This article was originally published on HCPLive.com.
A recent study presented at the Metabolic Institute of America's 19th Annual World Congress on Insulin Resistance, Diabetes, and Cardiovascular disease suggests a management approach involving triple therapy could lower risk of adverse hepatic outcomes in patients with new-onset type 2 diabetes.
Led by Olga Lavrynenko, MD, University of Texas Health Science at San Antonio, the study found patients in the EDICT study treated with triple therapy, which included metformin, exenatide, and pigolitazone, had less hepatic steatosis and fibrosis and significantly improved insulin sensitivity versus conventional therapy after a period of 6 years.
Background on EDICT defined the study as an ongoing randomized controlled trial taking place at the Texas Diabetes Institute, working to compare 2 therapeutic approaches for the management of patients with new-onset T2D.
Initial study protocol was designed for 3-years of follow-up and was extended to 6-years of follow-up. Measurements of FPG, FPI, HbA1c, OGTT, and body fat were measured at baseline and study end. Additionally, 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 vibration-controlled transient elastography (VCTE) measurement at the end of study to provide a measure of liver fibrosis (LSM) and hepatic steatosis (CAP).
From the LSM value, the severity of fibrosis was graded as <6 (F0, normal), 6 - 8 (F1/2), 8 - 12 (F3), and 12+ (F4, cirrhosis). Based on the CAP value (dB/m), the severity of hepatic steatosis was graded as either 100 - 233 (S0), 234 - 268 (S1), 269 - 300 (S2), and 300 + (S3).
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 diabetes duration of 4.5±1.1 months. Then, 29 patients were in triple therapy, with a mean age of 50 ± 2 years and diabetes duration of 5.4 ± 1.4 months.
Data show a total of 27 of 39 (69%) subjects receiving conventional therapy had grade 2 or 3 stenosis (S2, n = 9; S3, n = 18), while 9 of 29 (31%) had it in triple therapy (S2, n = 2; S3, n = 7), all P <.01.
In addition, 10 of 39 patients (26%) receiving conventional therapy had grade 3 or 4 fibrosis (F3, n = 7; F4, n = 3), versus 2 of 29 (7%) in triple therapy (F3, n = 2), all P = .003.
Lavrynenko and colleagues noted that triple therapy increased Matsuda index scores of insulin sensitivity 3-fold, while conventional therapy had no effect on insulin sensitivity.
The severity of steatosis, measured by CAP (r = .42, P <.001) and severity of fibrosis measured by LSM (r = -.48, P <.001) correlated inversely with Matsuda Index of insulin sensitivity. Further, the severity of steatosis by MRI-PDFF correlated with insulin resistance (r = .42, P <.05).
Two key data points showed hepatic steatosis and fibrosis were inversely correlated with insulin resistance, while antidiabetic agents that improve insulin resistance reduced hepatic fat and prevented fibrosis.
“T2DM subjects treated with triple therapy had less hepatic steatosis and fibrosis and markedly improved insulin sensitivity versus conventional therapy after 6 years,” investigators wrote.
“Hepatic Steatosis, Fibrosis, and Insulin Resistance: Implications for Therapy,” was published online by WCIRDC.