What is the maximum dose of semaglutide for weight loss?

The maximum FDA-approved dose of semaglutide for weight management (Wegovy) is 2.4 mg administered subcutaneously once weekly. This dose was used in the STEP clinical trial program and was associated with approximately 15–17% mean body weight reduction over 68 weeks. Compounded formulations may be dosed up to 2.5 mg weekly in some clinic protocols, though this exceeds the studied branded dose.

How long does the semaglutide titration take?

The standard weight management titration from 0.25 mg to 2.4 mg takes 16 weeks when escalating every 4 weeks (0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg). For type 2 diabetes dosing, reaching the 1.0 mg maintenance dose takes 8 weeks. If gastrointestinal side effects are significant, dose escalation may be delayed, extending the titration timeline.

Does semaglutide need to be injected at the same time each day?

Semaglutide is a once-weekly injection, not daily. It should be injected on the same day each week, but the time of day does not need to be consistent. If the scheduled day is missed, the injection can be administered within 5 days of the missed dose. If more than 5 days have passed, skip the missed dose and resume on the next scheduled day.

What happens when you stop taking semaglutide?

Data from the STEP 1 trial extension show that participants who discontinued semaglutide after 68 weeks regained approximately 11.6 percentage points of body weight over the following year, recovering about two-thirds of the initial loss. Metabolic improvements in blood pressure, lipids, and glycemic markers also partially reversed. This finding is consistent across GLP-1 agonist trials and has informed the clinical consensus that obesity pharmacotherapy is a long-term treatment.

Can oral semaglutide be used for weight loss?

Oral semaglutide (Rybelsus) at the 14 mg dose is currently approved only for type 2 diabetes. However, higher oral doses (25 mg and 50 mg daily) were evaluated in the OASIS 1 trial for weight management and demonstrated significant weight reduction (15.1% with 50 mg at 68 weeks). An oral formulation for obesity is being pursued for regulatory approval, but as of the current date, off-label use of Rybelsus for weight loss involves a lower dose than what clinical trials suggest is optimal.

How do you reconstitute compounded semaglutide?

Compounded semaglutide arrives as a lyophilized powder. Add the specified volume of bacteriostatic water (typically 2 mL) slowly along the vial wall — do not shake vigorously. Gently swirl or roll the vial until the powder is fully dissolved and the solution is clear. Refrigerate the reconstituted vial and use within 28 days. Always clean the vial stopper with an alcohol swab before each draw.

Semaglutide Dosage Chart & Titration Guide

Overview

Semaglutide is a GLP-1 receptor agonist that mimics the incretin hormone glucagon-like peptide-1, promoting insulin secretion, suppressing glucagon release, and slowing gastric emptying. It was initially developed and approved for type 2 diabetes (Ozempic, 2017) and subsequently for chronic weight management (Wegovy, 2021) after the landmark STEP clinical trial program demonstrated mean body weight reductions of 14.9% to 17.4% at 68 weeks. An oral formulation (Rybelsus) is also available for type 2 diabetes, using a novel absorption enhancer (SNAC) to enable GI absorption of the peptide. Compounded injectable semaglutide, supplied as lyophilized powder, has become widely available through telehealth clinics and requires reconstitution before use. As with all GLP-1 agonists, a gradual dose titration schedule is considered essential to minimize the well-documented gastrointestinal side effects.

Dosing Protocols

Weight Management Titration (Wegovy Protocol)

Route: Subcutaneous injection (abdomen, thigh, or upper arm)

Dose: 0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg

Frequency: Once weekly (same day each week), escalating every 4 weeks

Duration: 16 weeks to reach maintenance dose of 2.4 mg; ongoing thereafter

The 0.25 mg dose is for initiation only and is not considered therapeutic for weight loss. In the STEP 1 trial, the 2.4 mg weekly maintenance dose produced a 14.9% mean body weight reduction at 68 weeks versus 2.4% for placebo. If dose escalation is not tolerated, holding at the current dose for an additional 4 weeks before reattempting escalation is a commonly discussed approach.

Type 2 Diabetes (Ozempic Protocol)

Route: Subcutaneous injection

Dose: 0.25 mg → 0.5 mg → 1.0 mg (→ 2.0 mg if additional glycemic control needed)

Frequency: Once weekly, escalating every 4 weeks

Duration: Ongoing as part of diabetes management

For type 2 diabetes, the standard maintenance dose is 0.5 mg or 1.0 mg weekly. The 2.0 mg dose was added later for patients requiring additional glycemic control. All doses demonstrated statistically significant HbA1c reductions compared to placebo in the SUSTAIN trial program.

Oral Semaglutide (Rybelsus Protocol)

Route: Oral tablet — taken on empty stomach with no more than 4 oz plain water

Dose: 3 mg → 7 mg → 14 mg

Frequency: Once daily, at least 30 minutes before first food, drink, or other oral medications

Duration: 30 days at each dose level before escalation; ongoing

Oral semaglutide uses sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) to enhance absorption. Bioavailability is approximately 1% and is highly dependent on fasting conditions. Taking the tablet with food or more than 4 oz of water significantly reduces absorption. The 3 mg dose is for initiation only.

Compounded Injectable (Typical Clinic Protocol)

Route: Subcutaneous injection

Dose: 0.25 mg → 0.5 mg → 1.0 mg → 1.5 mg → 2.0 mg → 2.5 mg

Frequency: Once weekly, escalating every 4 weeks

Duration: 20–24 weeks to reach maximum dose; ongoing

Compounded semaglutide dose steps may differ slightly from branded products. Concentration depends on reconstitution volume. Always verify concentration (mg/mL) before drawing dose to avoid errors. Some compounded formulations include B12 or other additives.

Reconstitution & Storage

Vial sizes	2 mg, 5 mg, and 10 mg lyophilized vials (compounded forms vary)
Recommended water volume	Typically 2 mL bacteriostatic water (BAC water) per vial. A 5 mg vial reconstituted with 2 mL yields 2.5 mg/mL — draw 0.1 mL for a 0.25 mg dose, 0.2 mL for 0.5 mg, etc.
Storage	Refrigerate reconstituted solution at 36–46 °F (2–8 °C). Protect from light. Do not freeze.
Stability once reconstituted	Reconstituted compounded semaglutide is generally considered stable for up to 28 days when properly refrigerated. Branded pre-filled pens (Ozempic, Wegovy) may be stored at room temperature for up to 56 days after first use per prescribing information.

Use our reconstitution calculator to determine exact syringe units for your dose.

Cycle Guidance

Semaglutide is not cycled in clinical practice — it is used continuously for as long as the therapeutic benefit is desired. The STEP 1 trial extension data and the STEP 5 trial (104-week data) demonstrated that continued use was associated with sustained weight loss, while the STEP 1 trial extension showed that participants who discontinued semaglutide at 68 weeks regained approximately two-thirds of their lost weight over the following year. This has led researchers and clinicians to characterize obesity treatment with GLP-1 agonists as a chronic, ongoing therapy rather than a time-limited course. For individuals who wish to discontinue, a gradual taper (reverse titration over 8–12 weeks) has been discussed in clinical practice settings, though controlled data on tapering protocols are limited.

Stacking Considerations

Do not combine with other GLP-1 receptor agonists (tirzepatide, liraglutide, dulaglutide) — overlapping mechanisms increase adverse event risk without established additional benefit.
Semaglutide has been studied in combination with metformin, SGLT2 inhibitors, and sulfonylureas in the SUSTAIN trial program for type 2 diabetes. Sulfonylurea dose reduction may be needed to reduce hypoglycemia risk.
Gastric emptying delay caused by semaglutide may alter absorption of oral medications. Levothyroxine, oral contraceptives, and warfarin are commonly cited examples where monitoring is advised.
Some practitioners discuss combining semaglutide with naltrexone or topiramate for weight management, though robust clinical trial data supporting these specific combinations are limited.
Concurrent use with insulin requires caution — insulin dose reduction is commonly recommended when initiating semaglutide to mitigate hypoglycemia risk.

Potential Side Effects

Nausea (reported in 44% of participants at the 2.4 mg dose in STEP 1, most common during dose escalation, typically diminishing over time)
Diarrhea (reported in approximately 30% of participants in weight management trials)
Vomiting (reported in approximately 25% of participants at the 2.4 mg dose)
Constipation (reported in 24% of participants in STEP 1)
Abdominal pain and dyspepsia
Headache and fatigue (reported at higher rates than placebo)
Injection site reactions (erythema, pain — generally mild)
Gallbladder events (cholelithiasis, cholecystitis — associated with rapid weight loss)
Pancreatitis (rare but included in prescribing information warnings)
Potential for muscle mass loss alongside fat loss (discussed in body composition sub-studies)

Contraindications & Cautions

Personal or family history of medullary thyroid carcinoma (MTC) — based on thyroid C-cell tumor signal observed in rodent studies at supratherapeutic exposures
Multiple endocrine neoplasia syndrome type 2 (MEN 2)
Known hypersensitivity to semaglutide or any product excipients
History of pancreatitis (relative contraindication — requires careful risk-benefit assessment)
Severe gastroparesis or other severe gastrointestinal motility disorders
Pregnancy (animal studies suggest risk; discontinue at least 2 months before planned conception)
End-stage renal disease (limited data; not recommended in severe renal impairment without close monitoring)

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References

Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) (2021) — PubMed
Two-Year Effects of Semaglutide in Adults with Overweight or Obesity (STEP 5) (2022) — PubMed
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance (STEP 3) (2021) — PubMed
Withdrawal of Once-Weekly Semaglutide 2.4 mg and Weight Regain (STEP 1 Extension) (2022) — PubMed
Oral Semaglutide 50 mg Taken Once a Day in Adults with Overweight or Obesity (OASIS 1) (2023) — PubMed