Tirzepatide Shows Significant Reduction in Liver Fat Content in Patients with T2D

Tirzepatide was associated with a significant reduction in liver fat content (LFC), volume of visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT) in patients with type 2 diabetes (T2D), according to new findings.

Data was obtained from a subpopulation of the randomized, open-label, phase 3 SURPASS-3 study to characterize the changes in LFC, VAT, and ASAT in response to the study drug or insulin degludec.

“These data provide additional evidence on the metabolic effects of this novel GIP and GLP-1 receptor agonist,” wrote study author Ángel Rodríguez, MD, Lilly Spain.

The trial was performed at 45 medical research centers and hospitals across 8 countries, including Argentina, Austria, Greece, Hungary, Italy, Romania, Spain, and the USA. Eligibility criteria included:

• baseline HbA1c 7.0 - 10.5% (53 - 91 mmol/mol)
• BMI ≥25 kg/m2
• stable weight
• Insulin-naive
• Treatment with metformin alone or in combination with SGLT2 inhibitor for ≥3 months before screening

As an addition to the main study inclusion criteria, those in the substudy had a fatty liver index of ≥60. In the main study, participants had a MRI scan and were randomized in the main study to subcutaneous injection once-weekly of tirzepatide 5 mg, 10 mg, or 15 mg, or subcutaneous injection once per day of titrated insulin degludec.

These were stratified by country, HbA1c, and concomitant oral antihyperglycemic medication. A primary efficacy endpoint was identified as the change from baseline in LFC (measured by MRI-proton density fat fraction [MRI-PDFF]) at week 52 using pooled data from the tirzepatide 10 mg and 15 mg group, in comparison to insulin degludec.

Investigators noted the analyses were assessed in the enrolled MRI population, made up of patients in the modified intention-to-treat population of the main study who had a valid MRI at baseline or after baseline.

From April 2019 to November 2019, a total of 502 participants were assessed for inclusion, of which 296 (59%) were included in the enrolled MRI population and randomized to treatment (tirzepatide 5 mg, n = 71; tirzepatide 10 mg, n = 79; tirzepatide 15 mg, n = 72; and insulin degludec, n = 74). Both baseline and clinical characteristics were found to be similar across each treatment group.

At an overall mean baseline LFC of 15.71%, data show the absolute reduction in LFC at week 52 was significantly greater for the pooled tirzepatide 10 mg and 15 mg groups (-8.09%) versus the insulin degludec group (-3.38%). As such, the estimated treatment difference compared to insulin degludec was -4.71 (95% CI, -6.72 to -2.70; P <.0001).

Additionally, the reduction in LFC was found to be significantly correlated with baseline LFC (P = -0.71), reductions in VAT (P = .29), reduction in ASAT (P = .33), and reduction in body weight (P = .34) in the tirzepatide groups.

The study, “Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes: (SURPASS-3 MRI),” was published in The Lancet Diabetes & Endocrinology.