Three different clocks
Asking whether a GLP-1 medicine is "working yet" mixes three timelines. One is pharmacology: how quickly the drug builds up in the blood. One is the dose schedule: most labels start low and raise the dose over weeks or months. The last is the outcome a trial measured, such as weight or HbA1c, checked at fixed time points.
Keeping them apart makes trial results easier to read and conversations with your prescriber clearer.
Drug levels: hours to peak, weeks to settle
Each label’s pharmacokinetics section gives the time to the highest level after a dose and, for most, how long regular dosing takes to reach a steady level. A steady level only means the ups and downs repeat in a stable pattern at that dose; each increase starts the climb again.
Feeling a difference is a separate matter. In its section on diabetes, MedlinePlus says it may take 4 weeks or longer before people feel the full benefit of tirzepatide [8].
| Medicine | Peak after a dose | Steady level | Half-life | Source |
|---|---|---|---|---|
| Ozempic® injection (semaglutide) | 1 to 3 days | after 4 to 5 weeks of weekly doses | about 1 week | [5] |
| Rybelsus® and Ozempic® tablets (semaglutide) | about 1 hour | after 4 to 5 weeks of daily tablets | about 1 week | [9] |
| Wegovy® tablets (semaglutide) | 1 hour | not stated as a time | about 1 week | [3] |
| Zepbound® (tirzepatide) | median 24 hours (8 to 72) | after 4 weeks of weekly doses | about 5 to 6 days | [4] |
| Trulicity® (dulaglutide) | 24 to 72 hours, median 48 | between 2 and 4 weeks | about 5 days | [10] |
| Saxenda® (liraglutide) | 11 hours | not stated as a time | about 13 hours | [6] |
| Foundayo™ (orforglipron) | 4 to 8 hours | after about 1 week of daily tablets | about 29 to 49 hours | [11] |
The dose climbs for months
The labels describe a step-by-step increase, mainly to reduce stomach side effects. The Wegovy® injection starts at 0.25 mg and moves up every 4 weeks, so its escalation table reaches the maintenance stage at week 17; the tablets move up every 30 days and reach 25 mg on day 91 [3]. The Zepbound® label starts at 2.5 mg for 4 weeks and allows 2.5 mg increases once each dose has been used for 4 weeks or more [4]. Foundayo™ also steps up no sooner than every 30 days, and Saxenda® reaches 3 mg in week 5 [6][11].
In SURMOUNT-1 escalation lasted up to 20 weeks, and in STEP 1 the first 16 weeks, so much of the first months is spent below the doses the trials were built around [2][3]. Your prescriber sets the actual pace.
When side effects tend to appear
The early weeks are also when stomach side effects are most likely. In the Ozempic® trials, most reports of nausea, vomiting and diarrhea came during dose escalation, and the Zepbound® label says the same, adding that they decreased over time [4][5].
The tirzepatide and orforglipron labels add a related detail: the slowing of stomach emptying is largest after the first dose and becomes smaller with time [4][11]. Neither label gives a time for appetite changes, so we do not either.
What STEP 1 measured with semaglutide
STEP 1 enrolled 1,961 adults with overweight or obesity and without diabetes, and compared weekly semaglutide 2.4 mg with placebo for 68 weeks, alongside a lifestyle programme. At week 68, average body weight had changed by −14.9% with semaglutide and −2.4% with placebo; 86.4% versus 31.5% of participants had lost at least 5% [1].
The Wegovy® label shows the time course for this trial (Study 2) in a figure. Average weight falls steadily through most of the trial and levels off over the final months, while the placebo line stays close to its starting point [3].
What SURMOUNT-1 measured with tirzepatide
SURMOUNT-1 assigned 2,539 adults with obesity, or overweight with a weight-related condition, and without diabetes, to weekly tirzepatide 5 mg, 10 mg, 15 mg or placebo for 72 weeks. At week 72 the average change was −15.0%, −19.5% and −20.9% for the three doses and −3.1% with placebo [2].
The Zepbound® label figure for this trial shows the tirzepatide curves separating from placebo at the first visits, falling most steeply during the first half of the trial and flattening over the last months. The label notes that results were assessed after 72 weeks, with at least 52 weeks at the maintenance dose [4].
The tablets on their own timelines
- Wegovy® tablets: in Study 7 the dose was raised to 25 mg over 12 weeks and then held for 52, and weight was measured at week 64. The average change was −13.6% against −2.4% on placebo, and 76.3% against 31.3% lost at least 5% [3].
- Foundayo™: in Trial 1, people without diabetes were followed for 72 weeks. On the highest dose, 17.2 mg, the average change was −11.1% against −2.1% on placebo, and the label plots the change over time in its Figure 1 [11].
- A tablet’s faster peak does not mean a faster result in these trials: both programs judged weight after more than a year, as the injection trials did [3][11].
Beyond the end of the main trials
The 68- and 72-week time points are not where weight change stops in every case. In a prespecified analysis of SELECT, which ran for several years in people with heart disease and without diabetes, weight on semaglutide kept falling over about 65 weeks and the reduction was sustained for up to four years; at 208 weeks the mean change was −10.2% against −1.5% on placebo [12].
SELECT enrolled a different population from STEP 1, adults with existing heart disease and overweight or obesity, so its numbers should not be compared directly with the obesity trials [12].
Blood sugar runs on its own timeline
For type 2 diabetes, the glycemic trials in the Ozempic® label measured HbA1c, a blood test that reflects average glucose over recent months. In the monotherapy trial, HbA1c fell by 1.4 and 1.6 percentage points with 0.5 mg and 1 mg at week 30, compared with 0.1 with placebo [5].
Its pharmacodynamic tests, such as 24-hour glucose profiles, were done after 12 weeks of treatment including dose escalation [5]. In SURPASS-2, which compared tirzepatide with semaglutide 1 mg, HbA1c was measured at week 40 and fell by 2.01 to 2.30 points with tirzepatide against 1.86 with semaglutide [13]. Which measure to look at, and when, is for your care team.
Checkpoints in labels and guidance
Some sources name a review point. The US Saxenda® (liraglutide) label tells prescribers to evaluate weight change 16 weeks after starting and to stop if the person has not lost at least 4% of baseline weight; the EU document instead counts 12 weeks on the 3.0 mg dose and uses 5% [6][14]. NIDDK, part of the US National Institutes of Health, says most weight loss with these medicines takes place within the first 6 months [7].
NIDDK also describes a 12-week review once you reach the full dose: if weight has dropped by less than 5% by then, your health care professional is likely to suggest stopping or changing the plan [7]. Your clinician applies these checkpoints; results vary by medication and by person.
Ozempic®, Wegovy®, Rybelsus® and Saxenda® are registered trademarks of Novo Nordisk A/S. Zepbound® and Trulicity® are registered trademarks and Foundayo™ is a trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Novo Nordisk or Eli Lilly and Company.
