# Semaglutide Research: The Trial Record, Read in Full > Semaglutide research, staged by trial: STEP weight loss, SUSTAIN and SELECT cardiovascular, FLOW kidney, and the 2025 ESSENCE liver/MASH data. Cited, with semaglutide vs tirzepatide and compounded semaglutide read plainly. Liver, weight, cardiovascular, and kidney outcomes — each finding versioned to its source, with evidence status stated plainly. ## The short version Semaglutide research is unusually broad for one molecule. This page reads the big controlled trials one at a time and labels how strong each is. The headline here is the liver: a 2025 trial called ESSENCE found that in people with a serious fatty-liver disease (MASH), the liver inflammation cleared in about 63 out of 100 on the drug versus about 34 out of 100 on a dummy treatment. On top of that, large trials show real weight loss (about 15% of body weight in one study), fewer heart attacks and strokes in at-risk people, and slower kidney decline in diabetes. The semaglutide research record also includes honest comparisons — a 2025 head-to-head found a competing drug, tirzepatide, produced more weight loss. Every number below is tied to a published study you can look up. ## Liver and MASH: the ESSENCE result The leading finding in this digest is hepatic. The ESSENCE phase-3 trial (n=1,197; interim analysis n=800) enrolled adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and stage 2-3 fibrosis. MASH is an advanced form of fatty liver disease in which fat accumulation drives inflammation and progressive scarring (fibrosis). Once-weekly subcutaneous semaglutide 2.4 mg achieved resolution of steatohepatitis without worsening of fibrosis in 62.9% of participants versus 34.3% with placebo (a 28.7-percentage-point difference, P<0.001), and fibrosis improvement without worsening of steatohepatitis in 36.8% versus 22.4% (a 14.4-point difference, P<0.001) [1]. This is a controlled-human-trial result with histologic — biopsy-confirmed — endpoints, which is the strongest form of evidence for a liver-disease claim. It anchored the 2025 MASH indication. ## Semaglutide weight loss The weight evidence is anchored by the STEP program. In STEP 1, once-weekly subcutaneous semaglutide 2.4 mg produced a mean body-weight change of -14.9% from baseline to week 68 versus -2.4% with placebo in adults with overweight or obesity without diabetes — a treatment difference of roughly 12.4 percentage points [2]. STEP 5 extended this to two years, reporting sustained, clinically meaningful weight loss versus placebo [13], and STEP TEENS reported significantly greater BMI reduction than placebo in adolescents with obesity [14]. The weight evidence comes with a documented limitation: durability depends on continued treatment. In the STEP 4 randomized-withdrawal design, continuing semaglutide led to further weight loss whereas switching to placebo led to regain [15], and the STEP 1 extension reported a mean regain of roughly 11.6 percentage points of body weight within one year of stopping, with cardiometabolic improvements reverting toward baseline [16]. The record frames obesity pharmacotherapy as a chronic, not curative, intervention. ## Cardiovascular and kidney outcomes The cardiovascular record spans two populations. In SUSTAIN-6 (n=3,297), once-weekly semaglutide reduced the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.74; 95% CI 0.58-0.95) in type 2 diabetes at high cardiovascular risk; the same trial recorded significantly higher rates of diabetic-retinopathy complications (HR 1.76; 95% CI 1.11-2.78) [3]. In SELECT (n=17,604), semaglutide 2.4 mg reduced that composite by 20% (HR 0.80; 95% CI 0.72-0.90; P<0.001) in adults with established cardiovascular disease and obesity but without diabetes [4], a benefit a secondary analysis reported as independent of baseline glycemic status [17]. The kidney evidence comes from FLOW (n=3,533), where semaglutide 1.0 mg reduced major kidney-disease events — kidney failure, a 50% or greater decline in eGFR, or kidney or cardiovascular death — by 24% (HR 0.76; 95% CI 0.66-0.88) in type 2 diabetes with chronic kidney disease [5]. These are controlled-human-trial outcomes; the retinopathy finding is the one cardiovascular-trial signal that runs the other way and is documented as a caution on the [Semaglutide effects](/effects) page. ## Semaglutide vs tirzepatide On the semaglutide vs tirzepatide question, the record is direct. In the SURMOUNT-5 head-to-head trial (n=751) of adults with obesity, tirzepatide — a dual GIP/GLP-1 receptor agonist — produced greater mean weight loss than semaglutide at 72 weeks (-20.2% vs -13.7%; difference statistically significant, P<0.001) [18]. The same direction appeared earlier in type 2 diabetes: in SURPASS-2, tirzepatide produced greater reductions in HbA1c and body weight than once-weekly semaglutide 1.0 mg [19]. The honest reading is that for weight magnitude, the available head-to-head evidence favours tirzepatide, while semaglutide carries the larger and longer cardiovascular-outcomes record. The two compounds are different molecules and are not interchangeable. ## Compounded semaglutide Compounded semaglutide refers to semaglutide prepared by a compounding pharmacy rather than the approved manufactured product. During a federally declared shortage from roughly 2022 to early 2025, such compounding was permitted; the FDA documented dosing errors, adverse events requiring hospitalization, and products containing unverified or non-pharmaceutical active ingredients. Once the shortage was declared resolved in early 2025, those compounding pathways were curtailed. The distinction matters for reading this record: every trial summarized on this page used the approved manufactured product. Compounded or non-pharmaceutical sources fall outside the approved-product evidence base and carry the documented quality and safety concerns above. This site reads the published literature and does not evaluate or point to any source. --- A documentation-grade reading of the semaglutide trial record — STEP, SUSTAIN, SELECT, FLOW, and the 2025 ESSENCE liver data — each finding versioned to its source and the approved-versus-compounded line drawn in full, by a publisher that prescribes nothing and sells nothing.