# Semaglutide: The Head-to-Head Trial Ledger | Telehealth Digest > Semaglutide lost the 2025 head-to-head: -13.7% vs tirzepatide's -20.2% over 72 weeks (SURMOUNT-5). But it cut cardiovascular events 20% in SELECT (n=17,604). The numbers, cited. -13.7% against -20.2% over 72 weeks in SURMOUNT-5 — and a 20% cut in cardiovascular events in 17,604 people. A data-forward reading of the trial record, every figure traced to its study. ## The short version **Semaglutide** is a once-weekly (or once-daily pill) medicine that copies a natural gut hormone called GLP-1, which tells your brain you are full and your pancreas to handle sugar. It is FDA-approved for type 2 diabetes, long-term weight management, lowering heart-attack and stroke risk in people with heart disease, and a fatty-liver condition called MASH. In the big STEP 1 study, people lost about 15% of their body weight over roughly 16 months [2]. In a 2025 face-off called SURMOUNT-5, the newer drug **tirzepatide** beat it on the scale — about 20% lost versus 14% [1]. But semaglutide has its own deep record: it cut serious heart events by 20% in a 17,604-person trial [3]. What people report — including the downsides like nausea and "sulfur burps" — is on [the effects page](/effects). This site reads the numbers and cites every one. It is a digest, not a clinic, and it offers no doses or prescriptions. ## The head-to-head result, stated plainly In **SURMOUNT-5**, the first large head-to-head trial of the two leading incretin drugs, 751 adults with obesity were randomized to semaglutide or tirzepatide for 72 weeks. Tirzepatide produced a mean weight change of -20.2% versus -13.7% for semaglutide — a ~6.5 percentage-point gap, statistically significant at P<0.001 [1]. That is the headline, and it is worth saying without softening: on body weight, in a direct comparison, tirzepatide won. The same pattern held in type 2 diabetes a year earlier. In **SURPASS-2**, tirzepatide produced greater reductions in both HbA1c (a three-month blood-sugar average) and body weight than once-weekly semaglutide 1.0 mg [9]. The full breakdown — every comparable figure, side by side — lives on the [semaglutide vs tirzepatide](/vs-tirzepatide) page. What follows here is the rest of the ledger, because weight on the scale is one column, not the whole accounting. ## Where semaglutide's numbers are strongest Cardiovascular outcomes are semaglutide's deepest evidence. In **SELECT** (n=17,604) — adults with established cardiovascular disease and overweight or obesity but no diabetes — once-weekly semaglutide 2.4 mg cut the composite of cardiovascular death, nonfatal heart attack and nonfatal stroke by 20% versus placebo (HR 0.80; 95% CI 0.72-0.90; P<0.001) [3]. That is a hard-endpoint outcome trial, not a weight number, and tirzepatide does not yet have a published equivalent. The diabetes outcome trial came first. In **SUSTAIN-6**, semaglutide reduced the same three-point cardiovascular composite by 26% (HR 0.74; 95% CI 0.58-0.95) in people with type 2 diabetes at high risk [4]. And in **FLOW** (n=3,533), once-weekly 1.0 mg reduced major kidney-disease events — kidney failure, a ≥50% drop in kidney function, or kidney/cardiovascular death — by 24% (HR 0.76; 95% CI 0.66-0.88) [5]. Read together, the ledger reads like this: tirzepatide leads on weight, semaglutide leads on the depth and breadth of its outcome evidence. Both statements are true at once. ## What is semaglutide, structurally **Semaglutide** is a 31-amino-acid peptide — a short protein chain — engineered as a long-acting copy of human GLP-1 (glucagon-like peptide-1), the gut hormone released after a meal that signals fullness and helps control blood sugar [27]. Native GLP-1 lasts about two minutes in the body. Two design changes fix that: a swapped amino acid at position 8 blocks the enzyme DPP-4 that would chew it up, and a fatty-acid "tail" makes it stick to albumin, the most abundant protein in blood, so it clears slowly. The result is a roughly one-week half-life — the structural reason a single weekly injection works [27]. Its molecular formula is C187H291N45O59 (molecular weight ~4,114 Da; CAS 910463-68-2). It comes two ways: a once-weekly shot under the skin, and a once-daily tablet paired with an absorption helper called SNAC [17]. The [Semaglutide research](/research) page traces the mechanism in full, and the [Semaglutide effects](/effects) page covers what people report and the cited safety cautions. ## What this digest is — and is not This is an editorial digest: a data-forward reading of the published semaglutide trial record, led by the head-to-head comparison against tirzepatide. Semaglutide is a real, FDA-approved medicine, and the content here summarizes peer-reviewed studies and approved-label facts. It is not medical advice, and it recommends no doses for any individual. The word "telehealth" in the domain is editorial framing for an availability-focused reading of the record — not a service. There is no clinic here, no prescriber, and nothing is sold. Every dose figure on this site appears as a study-design or labeling fact, in the third person, never as guidance. Browse the [Semaglutide references](/references) for the full source list. --- A data-forward reading of the semaglutide trial ledger, posted head-to-head against tirzepatide — every figure reconciled to its study, with no clinic at the desk and nothing here dosed or sold.