Hormonal
Inhibitors of hepatic lipogenesis (including ACLY, ACC, FAS, SCD1, and DGAT2 inhibitors) reduce liver fat content in MASLD, but some (like ACC inhibitors) may increase serum triglycerides, necessitating combination therapies (e.g., ACC + DGAT2 inhibitors) to mitigate adverse lipid effects.
Several new drugs target the liver's fat-making enzymes (like ACC and FAS). While they reduce liver fat, some can raise blood triglycerides. To avoid this, doctors may combine an ACC inhibitor with a DGAT2 inhibitor. These are still largely in clinical trials and are not yet first-line treatments compared to GLP-1 agonists.
While in clinical trials, firsocostat (GS-0976) showed benefit in the improvement of liver lipid accumulation, stiffness and serum liver enzymes, but also led to an increase in serum triglycerides [69, 70]. ... co-administration of ACC inhibitor PF-05221304 and DGAT2 inhibitor PF-06865571 has a stacked efficacy and successfully overcomes the obstacle of ACC [83], although ACC inhibitors alone have obvious adverse effects of elevating serum TG and activating SREBP1c.
Why this rating
Cites animal models and early-phase human trials with mixed safety/efficacy profiles.
Source
Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics
Yuxiao Jiang et al. · Lipids in Health and Disease · 2024
DOI 10.1186/s12944-024-02092-2
More from this paper
- GLP-1 receptor agonists (including semaglutide, liraglutide, dulaglutide, and tirzepatide) significantly reduce hepatic lipid content and improve liver histology (steatosis, inflammation, and fibrosis) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), primarily through weight loss and direct metabolic modulation.Good
- Resmetirom, a selective thyroid hormone receptor beta (THRβ) agonist, significantly reduces hepatic steatosis, liver fibrosis, and serum lipid levels (LDL, TG, ApoB) in patients with MASLD, particularly those with fibrosis.Good
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →