Full text is available at the source.
The lancet. Diabetes & endocrinology···
Tirzepatide versus insulin degludec effects on liver fat and belly fat in people with type 2 diabetes
Updated
Abstract
The absolute reduction in liver fat content (LFC) at week 52 was -8.09% for tirzepatide compared to -3.38% for insulin degludec.
- Tirzepatide 10 mg and 15 mg groups showed a significant reduction in LFC compared to insulin degludec.
- The estimated treatment difference in LFC reduction versus insulin degludec was -4.71%.
- Reductions in LFC were significantly correlated with baseline LFC levels and reductions in visceral and subcutaneous fat.
- Changes in body weight were also associated with the reduction in LFC in participants treated with tirzepatide.
Simplified
BACKGROUND: Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist under development for the treatment of type 2 diabetes. The aim of this substudy was to characterise the changes in liver fat content (LFC), volume of visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT) in response to tirzepatide or insulin degludec in a subpopulation of the SURPASS-3 study.
METHODS: This substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial was done at 45 medical research centres and hospitals across eight countries (Argentina, Austria, Greece, Hungary, Italy, Romania, Spain, and the USA). Eligible participants were adults with type 2 diabetes, a baseline HbA7·0-10·5% (53-91 mmol/mol), a BMI of at least 25 kg/m, stable weight, were insulin-naive, and on treatment with metformin alone or in combination with a SGLT2 inhibitor for at least 3 months before screening. In addition to the main study inclusion criteria, substudy participants had a fatty liver index of at least 60. Participants had an MRI scan and were randomised (1:1:1:1) in the main study to subcutaneous injection once per week of tirzepatide 5 mg, 10 mg, or 15 mg, or subcutaneous injection once per day of titrated insulin degludec, using an interactive web-response system, and were stratified by country, HbA, and concomitant oral anti-hyperglycaemic medication. The primary efficacy endpoint was the change from baseline in LFC (as measured by MRI-proton density fat fraction [MRI-PDFF]) at week 52 using pooled data from the tirzepatide 10 mg and 15 mg groups versus insulin degludec. Analyses were assessed in the enrolled MRI population, which consisted of participants in the modified intention-to-treat population of the main study who also had a valid MRI at either baseline or after baseline. This is a substudy of the trial registered with ClinicalTrials.gov, number NCT03882970, and is complete. 1c1c2
FINDINGS: From April 1, 2019, to Nov 15, 2019, 502 participants were assessed for eligibility to participate in this substudy, 296 (59%) of whom were included in the enrolled MRI population and randomly assigned to treatment (tirzepatide 5 mg, n=71; tirzepatide 10 mg, n=79; tirzepatide 15 mg, n=72; and insulin degludec, n=74). Baseline demographics and clinical characteristics were similar across all treatment groups. From an overall mean baseline LFC of 15·71% (SD 8·93), the absolute reduction in LFC at week 52 was significantly greater for the pooled tirzepatide 10 mg and 15 mg groups (-8·09%, SE 0·57) versus the insulin degludec group (-3·38%, 0·83). The estimated treatment difference versus insulin degludec was -4·71% (95% CI -6·72 to -2·70; p<0·0001). The reduction in LFC was significantly correlated (p≤0·0006) with baseline LFC (ρ=-0·71), reductions in VAT (ρ=0·29), reductions in ASAT (ρ=0·33), and reductions in body weight (ρ=0·34) in the tirzepatide groups.
INTERPRETATION: Tirzepatide showed a significant reduction in LFC and VAT and ASAT volumes compared with insulin degludec in this subpopulation of patients with type 2 diabetes in the SURPASS-3 study. These data provide additional evidence on the metabolic effects of this novel dual GIP and GLP-1 receptor agonist.
FUNDING: Eli Lilly and Company.
Related papers
Apr '22
Weekly tirzepatide compared to daily insulin degludec for blood sugar control in adults with type 2 diabetes measured by continuous glucose monitoring
top 1% journal
cited by 51 papers
randomized controlled trial
Aug '21
Weekly tirzepatide compared to daily insulin as add-on treatments for type 2 diabetes with metformin, with or without SGLT2 inhibitors
top 1% journal
cited by 536 papers
randomized controlled trial
Sep '22
Tirzepatide compared to insulin glargine and their effects on kidney health in type 2 diabetes
top 1% journal
cited by 242 papers
randomized controlled trial
Oct '21
Tirzepatide compared to insulin glargine in type 2 diabetes patients with higher heart risk
top 1% journal
cited by 544 papers
clinical trial, phase iii
Apr '22
Tirzepatide compared to placebo or semaglutide on insulin production and sensitivity in adults with type 2 diabetes
top 1% journal
cited by 219 papers
randomized controlled trial
Jun '21
Effectiveness and safety of tirzepatide, a new drug activating two blood sugar control systems, in people with type 2 diabetes
top 1% journal
cited by 876 papers
randomized controlled trial
Aug '22
Effectiveness and safety of tirzepatide alone versus dulaglutide in Japanese adults with type 2 diabetes
top 1% journal
cited by 190 papers
randomized controlled trial
Feb '23
Safety and effectiveness of once-weekly long-lasting insulin in people with type 2 diabetes already using daily insulin
top 1% journal
cited by 50 papers
randomized controlled trial
Aug '22
Safety and effectiveness of tirzepatide added to one oral diabetes medicine in Japanese patients with type 2 diabetes
top 1% journal
cited by 111 papers
randomized controlled trial
Mar '24
Tirzepatide's impact on body fat distribution in people with type 2 diabetes
cited by 26 papers
comparative study