Semaglutide: What It Is and How It Works

Semaglutide is a synthetic analogue of GLP-1 (glucagon-like peptide-1), a hormone the gut releases after a meal. It shares roughly 94% of its sequence with the human hormone. The remaining 6% is the entire point: those changes are what turn a molecule with a two-minute lifespan into one that is injected once a week.

The FDA approved it in December 2017 as Ozempic for type 2 diabetes, in September 2019 as Rybelsus in oral form, and in June 2021 as Wegovy for weight management.

How it works: one receptor, several effects

Unlike tirzepatide, which activates two receptors, semaglutide acts on the GLP-1 receptor alone. That single target produces effects in several tissues at once:

In the pancreas — it stimulates insulin secretion, but only when blood glucose is elevated, and it suppresses glucagon release. The glucose dependence is why the class carries a low intrinsic risk of hypoglycaemia.
In the stomach — it slows gastric emptying, so food stays in the stomach longer.
In the brain — GLP-1 receptors in the hypothalamus and brainstem are involved in appetite regulation and satiety signalling.

The three modifications that made it weekly

Native GLP-1 is destroyed within about two minutes by the enzyme DPP-4 (dipeptidyl peptidase-4), which cleaves it at the N-terminus. Deacon and colleagues demonstrated this degradation in humans in 1995, and it is the central obstacle to using the hormone itself as a medicine.

Semaglutide works around it with three changes:

Aib at position 8 — an unnatural amino acid at the exact site DPP-4 attacks, which blocks the cut.
A C18 diacid side chain attached through a spacer at position 26 — this binds reversibly to albumin, the most abundant protein in blood plasma.
A substitution at position 34 — so the fatty acid attaches only where intended.

Albumin behaves like a reservoir: it holds most of the circulating semaglutide and releases it slowly. The result is a half-life of roughly one week, which is what makes weekly administration practical.

What the trials found

STEP — body weight

STEP 1 followed 1,961 adults with overweight or obesity and without diabetes for 68 weeks. Mean change in body weight was approximately −14.9% on semaglutide versus −2.4% on placebo, alongside lifestyle intervention in both groups. About 86% of participants on semaglutide reached at least 5% weight loss.

SELECT — cardiovascular outcomes

SELECT enrolled 17,604 adults with established cardiovascular disease and overweight or obesity, but without diabetes, and followed them for a mean of about 40 months. The primary cardiovascular endpoint occurred in 6.5% of the semaglutide group versus 8.0% on placebo — a hazard ratio of 0.80.

This is the result that changed how the class is discussed: it separated the cardiovascular benefit from glucose control, in a population that did not have diabetes.

These are outcomes from controlled trials, run under defined protocols with medical supervision and specified eligibility criteria. They describe group averages, not an individual prediction, and they are not a basis for self-medication.

Side effects

The profile is predominantly gastrointestinal: nausea, diarrhoea, vomiting, constipation and reduced appetite. In the trials these clustered around periods of dose escalation and eased as the dose stabilised. A small proportion of participants discontinued because of adverse effects.

Contraindications, warnings and interactions — including the boxed warning on thyroid C-cell tumours observed in rodents — are set out in the official prescribing information listed under sources.

Why tracking matters

A weekly injection over a year is 52 events, each one easy to misremember. Three things repay consistent recording:

The exact date and time of each dose — so the interval is a fact rather than an estimate.
The strength used, particularly across a period of change.
Weight and subjective notes, so a trend becomes visible instead of isolated numbers.

That is what PeptCycle records: a calendar, reminders, injection history and a weight chart — stored locally on the device, with no account and no server.

Frequently asked questions

What is the difference between Ozempic and Wegovy?

Both contain semaglutide. They are different products with different approved indications and different maximum strengths — Ozempic was approved for type 2 diabetes, Wegovy for weight management. The molecule is the same.

Why is semaglutide injected once a week?

Three structural changes protect it from the enzyme DPP-4 and bind it reversibly to albumin in the blood. Albumin acts as a reservoir and releases the molecule slowly, giving a half-life of roughly one week.

Is semaglutide stronger than tirzepatide?

They act differently — semaglutide targets the GLP-1 receptor only, tirzepatide targets GIP and GLP-1. In the head-to-head SURPASS-2 trial, tirzepatide produced greater reductions in HbA1c and body weight, but the two have different profiles and were studied in different populations.

Does PeptCycle recommend semaglutide doses?

No. PeptCycle is a record-keeping and tracking tool. Every value is entered by the user, and the calculator only converts millilitres into syringe units. The app contains no recommended doses anywhere.

Sources

GLP-1IncretinsClinical researchWeight