Not losing weight on a GLP-1: questions for your clinician

A small loss happens in trials too

Trial results are averages, and the spread around them is wide. In STEP 1, semaglutide 2.4 mg with lifestyle support produced an average change of −14.9% over 68 weeks, yet 13.6% of people on it had not reached a 5% loss by the end ^[6]. That is the Wegovy® trial on its own terms.

SURMOUNT-1, the main Zepbound® weight trial, tells a similar story inside its own design: on 5, 10 and 15 mg of tirzepatide, 85%, 89% and 91% of participants reached at least 5% over 72 weeks, so a smaller group on each dose did not ^[7]. The two trials differ in length, population and design, and these figures are not a comparison between the medicines. NIDDK sums it up simply: results vary by medicine and by person ^[8].

Where you are in the dose schedule

GLP-1 doses are raised in steps, mainly to reduce stomach side effects. The Zepbound® label says its 2.5 mg starting dose is for beginning treatment and is not approved as a maintenance dose, and each later step comes no sooner than 4 weeks into the current one ^[4]. The Saxenda® label says its lower daily doses are for titration only ^[1]. In SURMOUNT-1, the period of stepping up lasted 20 weeks ^[7].

This is why the first weeks are not when results are judged. The Zepbound® and Wegovy® labels ask prescribers to weigh both treatment response and tolerability when choosing a maintenance dose, so side effects that hold the dose lower are part of that conversation too ^[4][5].

Review points in the labels, the EU documents and NIDDK

The table restates when each source asks for response to be checked. It explains the documents; it is not a timetable to apply to yourself, and the review is your prescriber’s.

How the medicine is being taken

• Missed or late doses: the Zepbound® label allows a missed dose within 4 days and otherwise skips it; the Wegovy® label restarts the dose climb at a lower dose after 2 or more weekly doses in a row are missed ^[4][5]. Gaps can change the schedule your prescriber planned.
• Tablets: the Wegovy® tablet is taken on an empty stomach in the morning with a little plain water, followed by at least 30 minutes before food, drinks or other tablets. The label’s pharmacology section reports higher absorption after a longer fast following the dose ^[5].
• Injection site: both labels ask you to rotate sites with each dose, and the Wegovy® label says the site can change without any dose adjustment ^[4][5].
• Appearance and storage: the Zepbound® label asks you to check that the solution is clear and colourless to slightly yellow and to follow its refrigeration and room-temperature limits ^[4]. Ask your pharmacist if a pen or vial may have been stored outside them.

Other things that can hold weight up

• Medicines: MedlinePlus names birth control pills, corticosteroids, some medicines for bipolar disorder, schizophrenia and depression, and some diabetes medicines ^[9]. NIDDK says a clinician may change other medicines that might be causing weight gain ^[8].
• Hormones and health conditions: an underactive thyroid, Cushing syndrome, polycystic ovary syndrome, menopause and pregnancy ^[9].
• Fluid: swelling from fluid in the tissues can add weight; it can come with menstruation, heart or kidney failure or some medicines ^[9].
• Age: MedlinePlus notes that metabolism slows with age ^[9].
• Daily life: NIDDK lists eating triggers and short sleep among things a lifestyle programme can work on ^[8].
• MedlinePlus is clear: do not stop a medicine you suspect of adding weight without talking to your provider ^[9].

What a clinician may do next

When weight loss is not enough, says the NIDDK, one of the US National Institutes of Health, a health care professional may change the treatment plan or try a different medicine, suggest a different lifestyle, activity or eating programme, change other medicines that might be adding weight, or refer you to discuss weight-loss surgery ^[8].

It also notes that most weight loss with these medicines takes place within the first 6 months ^[8]. A clinician may want to look at blood tests or hormone levels too; MedlinePlus lists both among the tests that unexplained weight gain can prompt ^[9].

What not to do on your own

An extra dose, a shorter gap between injections or an early step up can seem tempting. The Saxenda® label tells patients to follow the escalation schedule and not to exceed the recommended dose, and every label sets its own steps and maximum ^[1][4][5]. The same applies to stopping.

The FDA has adverse event reports from people prescribed compounded semaglutide or tirzepatide at doses beyond the approved labels, including faster increases, and it lists offers at deep discounts or prices that seem too good to be true among warning signs when buying online ^[10]. Our article on compounded GLP-1s covers this in more detail.

Questions to bring to your appointment

• Am I on a starting dose, still stepping up, or on a maintenance dose?
• When will we judge the response, and against what amount of loss?
• Could any of my other medicines or health conditions be playing a part, and is a blood test worth doing?
• Am I taking my medicine in the way the label describes, including tablets and missed doses?
• Would a dietitian or a structured lifestyle programme help?
• If this medicine is not working well enough, what are the other options?

Saxenda® and Wegovy® are registered trademarks of Novo Nordisk A/S. Zepbound® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Novo Nordisk or Eli Lilly and Company.

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