REFERENCE / THE RECORD
The semaglutide trial record, staged study by study
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 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.