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GLP-1 · Hub

Starting a GLP-1: what to know before the first injection

People start a GLP-1 by one of three routes: a prescription for an approved pen, a compounded version from a pharmacy, or a vial sold online as a research chemical. The risks differ a lot between them. This hub explains each route, then covers what all three share: the first weeks, protecting muscle, what happens when you stop, and the warnings on the labels.

Last updated November 3, 2026 · Reviewed by Grey Peptides Editorial Board · ✓ Every claim sourced · No products sold, no seller named

Track
Track 1: a prescribed GLP-1
Wegovy, Ozempic, Zepbound and Mounjaro: the labelled dose steps, the side-effect timeline, and when to call a doctor.
Track
Track 2: a compounded GLP-1
What compounding is, what FDA did after the shortages ended, and the dosing errors it has reported.
Track
Track 3: grey-market "research" GLP-1s
Retatrutide and other vials sold for research: no approved product, what published tests found, and what to read first.
📋 Key takeaways

Three routes, three levels of risk. An approved pen is made under an FDA-reviewed application and comes with a label. A compounded version is not FDA-approved: FDA does not review compounded drugs for safety, effectiveness or quality before they are sold. A vial sold "for research purposes" is, in FDA's words, of unknown quality and may be harmful.11

The first weeks are mostly about the stomach. In the semaglutide weight trials, nausea, diarrhoea, vomiting and constipation were the common side effects; most were mild to moderate, short-lived, and came during or just after the weeks when the dose was being raised.12 That is why every label starts low and steps up slowly.910

Some of the weight lost is lean mass. In a tirzepatide trial that scanned 160 people, about 75% of the weight lost was fat and 25% lean mass.5 Resistance training and enough protein are the best-supported ways to keep more of it.68

Most of the weight comes back if you stop. A year after semaglutide ended in STEP 1, people had regained about two-thirds of what they lost;1 in SURMOUNT-4, people switched from tirzepatide to placebo regained 14% of their body weight in a year.2

On this page

  1. The three tracks
  2. First time? Read in this order
  3. The first weeks: what to expect
  4. Protein and lean mass
  5. Stopping and weight regain
  6. Long-term risks the labels warn about
  7. Frequently asked questions
  8. Related on Grey Peptides
  9. Sources

The three tracks

A GLP-1 drug copies a gut hormone, glucagon-like peptide-1, that slows the stomach and turns down appetite. The ones people mean when they say "a GLP-1" are semaglutide (sold as Wegovy for weight and Ozempic for type 2 diabetes) and tirzepatide (Zepbound and Mounjaro), which also acts on a second hormone, GIP. Liraglutide is an older drug of the same class. Retatrutide and cagrilintide have no approved product: FDA says neither is a component of an approved drug, neither has been found safe and effective for any condition, and neither may be used in compounding.11

How you get the drug decides most of the risk, so this section is split into three tracks. Pick the one you are on, or the one you are weighing up:

  • Track 1: prescribed. A branded pen or vial from a pharmacy, on a prescription. The label sets the starting dose, the steps up and the warnings, and the page lays them out as the label prints them.910
  • Track 2: compounded. A pharmacy mixes its own version. These are not FDA-approved, and FDA says they should be used only by patients whose needs an approved drug cannot meet.11 The page covers what changed when the shortages ended and the dosing errors FDA has reported.
  • Track 3: grey-market "research" GLP-1s. Powder in a vial, bought online with no prescription and labelled for research. FDA calls these labels false when the products are sold for people.11 The page covers what published tests found inside such vials and what to read before you go further.

Whatever the track, the drug in the body works the same way, so the sections below apply to all three.

First time? Read in this order

Start with your track's page, then the shared sections on this page, then the tools and guides that go with them.

  1. Track 1: a prescribed GLP-1. Wegovy, Ozempic, Zepbound and Mounjaro: the labelled dose steps, the side-effect timeline, and when to call a doctor.
  2. Track 2: a compounded GLP-1. What compounding is, what FDA did after the shortages ended, and the dosing errors it has reported.
  3. Track 3: grey-market "research" GLP-1s. Retatrutide and other vials sold for research: no approved product, what published tests found, and what to read first.
  4. GLP-1 titration planner. Lays the labelled dose steps out on a calendar.
  5. GLP-1 pens, vials and dose math. How pens, vials and syringe marks relate.
  6. GLP-1s and muscle loss. The body-composition trials in more depth.
  7. Stopping a GLP-1 and weight regain. The withdrawal trials in more depth.
  8. GLP-1 drug interactions. Oral medicines, contraceptives, insulin and sulfonylureas.
  9. Reconstitution calculator. Vial, water and dose in; the syringe mark out.
  10. Syringes for first-timers. Buying syringes, sizes and units, injecting, disposal.

The first weeks: what to expect

The side effects people notice first are in the gut. Pooling three semaglutide weight trials (2,117 people on the drug), nausea was reported by 43.9% on semaglutide against 16.1% on placebo, diarrhoea by 29.7% against 15.9%, vomiting by 24.5% against 6.3%, and constipation by 24.2% against 11.1%.12 The same analysis found 98.1% of these events were mild to moderate, and that they were transient and came most often during or shortly after dose escalation; 4.3% of people stopped the drug because of them.12 The tirzepatide obesity trial reported the same pattern: gastrointestinal events, mostly mild to moderate, mainly while the dose was being raised.13

Put simply: the hardest stretch tends to be the start and each step up, not the months on a steady dose. That is the reason the labels begin with a low starting dose and step up no faster than every four weeks. The Wegovy label says to consider waiting another four weeks before a step that is not tolerated, and the Zepbound label to consider a lower maintenance dose.910 The prescribed track has the full timeline and the label's advice on nausea, constipation and dehydration.

Protein and lean mass

When anyone loses a lot of weight, some of it is lean mass, not fat. The clearest GLP-1 measurement comes from a substudy of SURMOUNT-1, in which 160 people had DXA body scans at the start and after 72 weeks. On tirzepatide, body weight fell 21.3%, fat mass 33.9% and lean mass 10.9%; on placebo the figures were 5.3%, 8.2% and 2.6%. In both groups about 75% of the weight lost was fat and 25% lean mass.5

Across 20 randomised trials with 15,782 people, a 2026 meta-analysis put lean mass at 35.2% of the weight lost on semaglutide, 25.4% on tirzepatide and 26.8% on liraglutide, close to the 26.2% seen with diet and lifestyle programmes. Lifestyle programmes that included resistance training did best, at 17.5%.6 Those drug figures come from different trials, not a head-to-head comparison.

Lean mass is not the same as muscle. It also counts organs, bone, fluids and the water held in fat tissue, and a 2024 review judged the muscle changes seen on MRI to be largely in line with the weight lost.7 Even so, older people and those already frail have more to lose.7

What helps: in a meta-analysis of 18 studies, eating more protein than the recommended minimum of 0.8 g per kg of body weight a day kept an average of 0.36 kg more lean mass during calorie restriction.8 Resistance training had the strongest effect in the incretin meta-analysis.6 Appetite falls on these drugs, so planning protein into smaller meals is the practical step (our reasoning). The muscle-loss guide goes further.

Stopping and weight regain

These drugs work while you take them. Three trials stopped the drug on purpose and watched what happened:

  • STEP 1 extension (semaglutide). After 68 weeks, treatment and the lifestyle programme stopped. In the 327 people followed for another year, those who had taken semaglutide had lost 17.3% of their weight and regained 11.6 percentage points of it by week 120, leaving a net loss of 5.6%: about two-thirds regained. Blood pressure, blood sugar and other improvements also drifted back toward where they started.1
  • STEP 4 (semaglutide). After 20 weeks on the drug (an average loss of 10.6%), 803 people were randomised to keep taking it or switch to placebo. Over the next 48 weeks those who continued lost a further 7.9%; those switched to placebo regained 6.9%.3
  • SURMOUNT-4 (tirzepatide). After 36 weeks at the highest tolerated dose, 670 people had lost 20.9%. Over the next 52 weeks, those who continued lost another 5.5%; those switched to placebo regained 14.0% of their weight. At week 88, 89.5% of the continuing group had kept at least 80% of their earlier loss, against 16.6% of the placebo group.2

Pooling 37 studies of weight-loss medicines, a 2026 BMJ meta-analysis found an average regain of 0.4 kg a month after stopping, faster than after diet and behaviour programmes, with heart and metabolic markers projected back at baseline within about 1.4 years.4 The STEP 1 authors' conclusion is the plain one: obesity behaves as a chronic condition, and keeping the benefit seems to need ongoing treatment.1 Anyone planning to stop, or forced to by cost or supply, should plan it with a prescriber; the stopping guide covers what has been tried.

Long-term risks the labels warn about

These warnings sit on the approved labels. They describe the molecule, so they apply whether a vial came from a pharmacy or anywhere else (our reasoning: compounded and grey-market products contain the same molecule or claim to, with no label of their own).

  • Thyroid C-cell tumours (boxed warning). Semaglutide and tirzepatide caused thyroid C-cell tumours in rodents. Whether they do so in people is unknown. Both drugs must not be used by anyone with a personal or family history of medullary thyroid carcinoma or with MEN 2. The labels list a lump in the neck, trouble swallowing, shortness of breath and persistent hoarseness as symptoms to report.910
  • Pancreatitis. Acute pancreatitis, including fatal cases, has been seen with these drugs. The warning sign is persistent, severe stomach pain, sometimes going through to the back, with or without vomiting; the labels say to stop the drug if pancreatitis is suspected.910
  • Gallbladder. Gallstones and gallbladder inflammation were more common on the drugs. In the Wegovy injection weight trials, gallstones were reported by 1.6% on Wegovy against 0.7% on placebo; in the Zepbound weight trials, gallbladder inflammation by 0.7% against 0.2%.910 Rapid weight loss raises the risk, but the Wegovy label says the excess remained after allowing for the amount lost.9
  • Kidneys, through dehydration. Kidney injury, some needing dialysis, has been reported, mostly in people who became dehydrated from nausea, vomiting or diarrhoea.910
  • Surgery and sedation. The drugs slow the stomach, and rare cases of food being breathed into the lungs under anaesthesia have been reported. Tell whoever is sedating you that you take one.910

The prescribed track turns these into a list of when to call a doctor.

Frequently asked questions

Which GLP-1 route is safest?

An FDA-approved product from a pharmacy on a prescription. It is the only one made under an application FDA reviewed, with a label giving its doses and warnings. FDA says compounded drugs are not reviewed for safety, effectiveness or quality before they are sold, and calls products labelled for research of unknown quality.11

Will I lose muscle on a GLP-1?

Some lean mass, yes. In a tirzepatide trial with body scans, about a quarter of the weight lost was lean mass, the same share as on placebo. Resistance training and protein above 0.8 g per kg a day help keep more of it.568

What happens when I stop?

Most people regain much of the weight. In the STEP 1 extension, people regained about two-thirds of their loss in the year after stopping semaglutide. In SURMOUNT-4, people switched to placebo regained 14% of their body weight in a year.12

Does Grey Peptides recommend a pharmacy, telehealth service or seller?

No. The site names no seller, sells nothing and rates no one.

Track 1: a prescribed GLP-1 Track 2: a compounded GLP-1 Track 3: grey-market "research" GLP-1s GLP-1 titration planner GLP-1 pens, vials and dose math GLP-1s and muscle loss Stopping a GLP-1 and weight regain GLP-1 drug interactions Reconstitution calculator Syringes for first-timers

Sources

Labels are cited by their DailyMed set and version; studies by PMID, checked on PubMed; FDA pages with the date they show. All read November 3, 2026.

  1. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. PMID 35441470. Read November 3, 2026. Source
  2. Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38-48. PMID 38078870. Read November 3, 2026. Source
  3. Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414-1425. PMID 33755728. Read November 3, 2026. Source
  4. West S, et al. Weight regain after cessation of medication for weight management: systematic review and meta-analysis. BMJ. 2026;392:e085304. PMID 41500720. Read November 3, 2026. Source
  5. Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025;27(5):2720-2729. PMID 39996356. Most authors worked for Eli Lilly, tirzepatide's maker. Read November 3, 2026. Source
  6. Eisa N, Barood O. Lean Mass Changes With Incretin Therapy Versus Lifestyle Intervention: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Diabetes Obes Metab. 2026;28(6):4818-4827. PMID 41877354. Read November 3, 2026. Source
  7. Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab. 2024;26 Suppl 4:16-27. PMID 38937282. Read November 3, 2026. Source
  8. Hudson JL, Wang Y, Bergia RE, Campbell WW. Protein Intake Greater than the RDA Differentially Influences Whole-Body Lean Mass Responses to Purposeful Catabolic and Anabolic Stressors: A Systematic Review and Meta-analysis. Adv Nutr. 2020;11(3):548-558. PMID 31794597. Read November 3, 2026. Source
  9. Wegovy injection (semaglutide) US prescribing information (Novo Nordisk; DailyMed set ee06186f, version 19, effective June 18, 2026): sections 2 (dosage), 5 (warnings: thyroid C-cell tumours, pancreatitis, gallbladder, kidney injury, aspiration) and the boxed warning. Read November 3, 2026. Source
  10. Zepbound (tirzepatide) US prescribing information (Eli Lilly; DailyMed set 487cd7e7, version 40, effective August 28, 2026): sections 2 and 5 and the boxed warning. Read November 3, 2026. Source
  11. U.S. Food and Drug Administration. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. Content current as of October 1, 2026; read November 3, 2026. Source
  12. Wharton S, Calanna S, Davies M, et al. Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Diabetes Obes Metab. 2022;24(1):94-105. PMID 34514682. Read November 3, 2026. Source
  13. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216. PMID 35658024. Read November 3, 2026. Source

This section explains GLP-1 medicines in plain words; it is not medical advice, and it does not replace the prescriber or pharmacist who knows your history. Grey Peptides sells nothing, links to no seller and rates none. If you feel unwell after an injection, contact a clinician or Poison Help (1-800-222-1222 in the US); in an emergency call 911.