Metabolism & Weight Loss

Semaglutid

Semaglutide is a prescription GLP-1 receptor agonist and an approved gold standard for treating type 2 diabetes and obesity, offering significant weight loss as well as cardiovascular and renal benefits.

Also seen on labels, in price lists and in the community as: SM

Editorial team ·Updated ·18 Sources ·evidence-rated ·independent & ad-free

Common use from studies

How this peptide is typically used - described, not recommended.

How much
0.25-2.4 mg per dose
How often
once a week
Administration
Injection

You inject semaglutide once a week, under the skin (subcutaneously). You start with 0.25 mg per week and increase the dose every four weeks. After about 16 weeks, you reach the target dose: 2.4 mg per week for overweight or 2.0 mg per week for diabetes. These dosing guidelines come from clinical studies of approved ready-made medications like Ozempic and Wegovy. Gray-market powder in vials for self-mixing with water is unproven: it lacks quality controls, and dosing is prone to errors.

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As of

  • Drug class: GLP-1 receptor agonist (incretin mimetic)
  • Main benefits: Significant weight loss, lower blood sugar, and reduced cardiovascular and kidney risks
  • Approval status: Fully approved (FDA/EMA) for type 2 diabetes, obesity (including adolescents aged 12 and up), CVD, and chronic kidney disease
  • Available forms: Subcutaneous (Ozempic, Wegovy), oral (Rybelsus, Wegovy tablet)

Semaglutide: How the GLP-1 Agonist Works and What It's Used For

Semaglutide is a prescription medication from the group of GLP-1 receptor agonists. It's widely seen as the gold standard among weight-loss injections. It's a peptide hormone analog, meaning it's a lab-made version of a natural hormone. It mimics the human gut hormone GLP-1 and matches it in 94% of its amino acid sequence. It's used to treat type 2 diabetes, obesity, and to reduce cardiovascular and kidney risks.

Semaglutide comes in two forms: as a subcutaneous injection (Ozempic for diabetes, Wegovy for obesity) and as an oral tablet (Rybelsus for diabetes since 2019, Wegovy tablet for obesity since December 2025). This makes semaglutide the first and so far only GLP-1 drug approved for weight loss both as an injection and as a pill.

How to Use Semaglutide: Injection (Shot) and Tablets

You can take semaglutide in two ways: as a shot under the skin (subcutaneous) or as a tablet (oral). The approved, evidence-based way is only as a finished pharmaceutical product - Ozempic, Wegovy, and Rybelsus are prescription medications.

Subcutaneous (Ozempic, Wegovy): You give the injection once a week under the skin, usually in the abdomen, thigh, or upper arm. Both products come as pre-filled pens with fixed doses - no mixing needed. The dose is increased slowly over about 16 weeks, starting at 0.25 mg per week up to a maximum target dose of 2.4 mg/week (obesity) or 2.0 mg/week (diabetes) [7, 9].

Oral (Rybelsus, Wegovy tablet): You take the tablet once a day on an empty stomach - at least 30 minutes before the first meal, drink, or other medication. Rybelsus (diabetes) is increased from 3 mg/day to 7 mg or 14 mg/day [19]. The Wegovy tablet (obesity) is increased up to 25 mg/day [23]. The oral bioavailability - how much of the drug actually reaches your bloodstream - is much lower than with the injection, which is why the tablet doses are much higher.

Gray market practice: On the gray market, lyophilized semaglutide powder in vials (5-30 mg) is sometimes offered. Users reconstitute it themselves with BAC water and inject it subcutaneously. This practice is unproven and risky: there is no quality control, dosing is error-prone, and sterility is not guaranteed. Semaglutide is regulated as a prescription medication - the gray market route is not compliant with approval.

Semaglutide Dosage: Reconstituting Vials and Calculation Examples

Since semaglutide is sold as a finished pharmaceutical product (pre-filled pen), mixing is usually not necessary. However, vials with lyophilized powder offered on the gray market do require reconstitution. The following example is purely for documentation and is not a recommendation.

Example calculation (unproven user practice): With a vial containing 10 mg of semaglutide powder reconstituted with 2 ml of BAC water, the resulting concentration is 5 mg/ml. For a dose of 0.25 mg (starting dose), you would draw up 0.05 ml (5 units on an insulin syringe U-100). For 1.0 mg, it would be 0.2 ml (20 units). These values are for illustration only and are not dosing instructions.

To correctly calculate doses from vials, you can use the Injection Calculator. General tips on mixing and storing can be found in the Guides.

How Semaglutide Works in the Body

Semaglutide mimics the human gut hormone GLP-1, with a 94% match in its amino acid sequence. It signals the pancreas to release insulin in a glucose-dependent manner while suppressing glucagon. Additionally, it slows stomach emptying, curbs appetite, and reduces so-called 'food noise' - the constant thoughts about eating. By binding to albumin in the blood, it achieves a half-life of 165 to 200 hours, which allows for once-weekly dosing.

Study Results on the Effectiveness of Semaglutide

The effectiveness of semaglutide is backed by one of the largest clinical programs in medical history. The key results:

AreaStudyResult
Weight lossSTEP program15-20% weight loss over 68 weeks [3, 7]
CardiovascularSELECT (NEJM 2024)~20% MACE reduction in obesity + CVD [16]
KidneyFLOW (NEJM 2024)24% reduction in the combined kidney endpoint in T2D + CKD [17]
Oral cardiovascularSOUL (Phase 3b, 2025)MACE reduction also for oral semaglutide [22]
Oral obesityOASIS 4 (Phase 3, 2025)~17% weight loss with 25 mg/day oral [23]
Alcohol addictionPhase 3 (2026)41.1 percentage point reduction in heavy drinking days vs. 27.4% placebo [24]

The STEP Program: Clinical Studies on Weight Loss

The STEP program (Semaglutide Treatment Effect in People with Obesity) includes numerous phase 3 studies with tens of thousands of participants in total. It consistently confirms weight loss of 15 to 20% over 68 weeks at the target dose of 2.4 mg/week subcutaneously. STEP-Teens extended the approval to adolescents aged 12 and up. STEP-HFpEF additionally showed benefits in heart failure with preserved ejection fraction and obesity [25].

Dosage Schedule and Titration of Semaglutide

The study-validated dosing of semaglutide uses slow titration to minimize gastrointestinal side effects.

IndicationFormStarting doseTarget doseTitration duration
Obesity (Wegovy)subcutaneous0.25 mg/week2.4 mg/week~16 weeks
T2D (Ozempic)subcutaneous0.25 mg/week0.5-2.0 mg/week~8-16 weeks
T2D (Rybelsus)oral3 mg/day7-14 mg/day~30+ days
Obesity (Wegovy tablet)oral1.5 mg/day25 mg/day~16 weeks

Titration is done in 4-week steps. If tolerated, you can move to the next level; if not, you can stay on a level longer.

Storage and Proper Handling of Ozempic and Wegovy

Semaglutide pre-filled pens are stored in the refrigerator at 2-8 °C. After first use, they can be kept at room temperature (up to 30 °C) for up to 6 weeks. The tablet must be stored dry at room temperature. Freezing is off-limits for both forms.

More details on proper storage and handling can be found in the Guides. If you want to calculate a dose from a vial, the Dose Calculator can help.

Side Effects and Risks of Using Semaglutide

The most common side effects of semaglutide affect the gastrointestinal tract, with nausea, vomiting, diarrhea, constipation, and bloating occurring very commonly during the dose escalation phase [2]. In clinical studies with Wegovy, 44% of patients reported nausea [2]. A meta-analysis confirms an increased risk of gallstone formation [6]. Rare but serious risks include pancreatitis and gastroparesis. In animal studies, thyroid C-cell tumors were observed; in humans, this link could not be confirmed [2, 7].

A common mistake is increasing the dose too quickly, which leads to severe gastrointestinal discomfort. Another mistake on the gray market is incorrectly reconstituting powder vials with unsuitable solvents or wrong concentrations.

Semaglutide is fully approved as a prescription medication. The key approval milestones:

YearApprovalProduct
2017T2D (subcutaneous)Ozempic
2019T2D (oral)Rybelsus
2021Obesity (subcutaneous)Wegovy
2024CVD risk reduction (SELECT)Wegovy
Jan 2025Chronic kidney disease (FLOW)Ozempic
Oct 2025CV risk reduction oral (SOUL)Rybelsus
Dec 2025Obesity (oral, OASIS 4)Wegovy tablet

Further studies are underway for MASH (an inflammatory fatty liver disease with liver scarring); approval is still pending. You can find more related drug profiles in the Peptide Library.

Evidence at a glance

Research status
Semaglutide is the subject of a comprehensive research program, ranging from preclinical studies in mice, rats, minipigs, and monkeys to large-scale clinical human trials [11]. Animal studies have shown that semaglutide distributes to brain regions and activates neurons there [4], with preclinical data also pointing to neuroprotective effects and a suppression of alcohol consumption [14]. In clinical human trials, the drug has demonstrated significant success in treating type 2 diabetes mellitus and obesity. The phase 3a programs SUSTAIN (subcutaneous) and PIONEER (oral) showed greater reductions in HbA1c levels and body weight than placebo or comparators [9, 19, 21]. The STEP program confirmed weight loss of 15-20% over a period of 68 weeks [3, 7]. The SELECT study (NEJM 2024) demonstrated a reduction in major adverse cardiovascular events (MACE) of about 20% in adults with obesity and existing CVD [16]. The FLOW trial (NEJM 2024) showed a 24% reduction in the composite endpoint of kidney failure, eGFR loss, and kidney or cardiovascular death in T2D and CKD [17]; based on this, the FDA expanded the approval for Ozempic in January 2025 to include chronic kidney disease [18]. The SOUL study (phase 3b, 2025) also showed cardiovascular benefits for oral semaglutide [22]. In December 2025, the Wegovy tablet (25 mg oral, OASIS 4) was approved as the first oral GLP-1 therapy for obesity [23]. A phase 3 study for treating alcohol addiction (2.4 mg/week, 26 weeks) found a reduction in heavy drinking days of 41.1 percentage points compared with 27.4% under placebo (p=0.0015) [24]. Studies on MASH with liver fibrosis are ongoing; approvals are still pending.
Human evidence
In clinical human studies, semaglutide has shown significant therapeutic effects in treating type 2 diabetes mellitus and obesity. The phase 3a programs SUSTAIN (subcutaneous) and PIONEER (oral) show that the drug lowers HbA1c levels and body weight more effectively than placebos or comparator drugs [9, 19, 21]. A phase 2 dose-finding study (0.05-0.4 mg subcutaneous) identified doses of 0.2 mg and 0.4 mg as particularly effective for weight loss [5]. The STEP program confirmed in several phase 3 studies a weight reduction of 15-20% over 68 weeks [3, 7]. The SELECT study (NEJM 2024, approx. 17,600 participants) demonstrated a reduction in the risk of major adverse cardiovascular events (MACE) by about 20% in adults with obesity and cardiovascular disease (CVD) [16]. In parallel, the FLOW trial (NEJM 2024, approx. 3,500 participants) documented a 24% reduction in the composite kidney endpoint in type 2 diabetes (T2D) and chronic kidney disease (CKD) [17]. For oral use, the SOUL study (phase 3b, 2025, approx. 9,650 participants) also demonstrated cardiovascular benefits [22]. For the oral Wegovy tablet (25 mg), the OASIS-4 study (phase 3, 64 weeks, 307 participants) showed a weight loss of approx. 17% compared to 3% with placebo [23]. Additionally, in a phase 3 study on alcohol addiction, semaglutide (2.4 mg/week, 26 weeks) reduced heavy drinking days by 41.1 percentage points (placebo: 27.4%; p=0.0015, NNT 4.3) [24].
Dosages in studies & practice
Semaglutide stays in your body for a long time: its half-life is about 160 hours. That's why a once-weekly dose is enough [7]. Studies and protocols use these doses: Subcutaneous: 2.4 mg once a week as the standard dose in RCTs for obesity/overweight (STEP program) [3, 4, 7]. 0.5 mg and 1.0 mg subcutaneously once a week as standard doses for T2D (SUSTAIN) [9, 19]. Titration: Start with 0.25 mg/week for 4 weeks, then 0.5 mg for >=4 weeks, then 1.0 mg, possibly 1.7 mg and 2.4 mg (obesity) or 2.0 mg (diabetes) [7, 9]. Oral (Rybelsus, diabetes): 3 mg/day for 30 days, then 7 mg/day, possibly 14 mg/day [19]. Oral (Wegovy tablet, obesity): titrate up to 25 mg/day [23]. On the gray market, lyophilized semaglutide powder is sometimes sold in vials (5-30 mg) and reconstituted at home with BAC water; this practice is unproven and risky.
Risks & side effects
The most common side effects of Wegovy (semaglutide) affect the stomach and intestines. You may notice nausea, vomiting, abdominal pain, constipation, or diarrhea. These complaints are the main reason people stop taking the medication [2]. In clinical studies, 44% of patients reported nausea [2], and a meta-analysis also found a higher risk of gallstone formation [6]. Rare but serious risks include pancreatitis, gastroparesis, and possible thyroid C-cell tumors (seen in animal studies, not confirmed in humans) [2, 7]. With gray market products, there are extra risks from contamination, incorrect dosing, and lack of sterility.
Research gaps
For harm-reduction contexts, such as alcohol or substance use, there is now a positive phase 3 study [24]. Still, long-term data and approvals are missing. Studies are underway for MASH with liver fibrosis, but approval is still pending. Long-term studies are still expected for safety over 5+ years. The oral form is less bioavailable than the subcutaneous one. Long-term data is also still missing for the Wegovy tablet, which has been available since December 2025.

Editorial, sourced from primary literature - not medical advice.

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