Semaglutide

Also known as: Ozempic, Wegovy, Rybelsus, NN9535

Evidence: Clinical

PeptideLab is an educational platform for learning about peptides. The information here is for educational and research purposes only. It is not medical advice, diagnosis, or treatment, and PeptideLab does not claim to diagnose, treat, cure, or prevent any disease or health condition. Many peptides discussed have not been approved for human use by the FDA or other regulatory bodies. Consult a qualified healthcare professional before making any health-related decision.

Overview

Acylated GLP-1 receptor agonist; FDA-approved for type 2 diabetes (2017) and obesity (2021). In STEP 1, 2.4 mg weekly gave 14.9% weight loss at 68 weeks versus 2.4% with placebo.

Semaglutide is a GLP-1(7-37) analog from Novo Nordisk with an Aib substitution at position 8 against DPP-4 breakdown and a C18 fatty diacid on Lys26 for albumin binding, giving a half-life of about one week (Lau 2015). In STEP 1, 2.4 mg weekly gave 14.9% weight loss over 68 weeks versus 2.4% (Wilding 2021); 7.2 mg gave 18.7% in STEP UP (Wharton 2025). SUSTAIN-6 (Marso 2016) and SELECT (Lincoff 2023) showed fewer cardiovascular events. FDA approvals: Ozempic for type 2 diabetes (2017), Rybelsus oral tablets (2019), Wegovy for weight (2021), with cardiovascular risk (2024), MASH (2025), Wegovy tablets (December 2025) and a 7.2 mg dose added later. All are marketed; one Ozempic presentation is discontinued.

Benefits

Weight loss (human RCTs; 14.9% at 2.4 mg, 18.7% at 7.2 mg), lower HbA1c in type 2 diabetes (human RCTs), 20% fewer major cardiovascular events in obesity (human RCT)

Dosing reference

Research dose: 0.25 to 2.4 mg once weekly subcutaneously (label titration and usual maintenance); the label also allows 7.2 mg weekly for weight
Range: 250 to 7200 mcg, 1x weekly
Reconstitution: 3 mL bacteriostatic water
Common vial sizes: 3 mg, 5 mg

Subcutaneous, once weekly, any time of day. Label titration starts at 0.25 mg weekly for 4 weeks and steps up every 4 weeks to the 2.4 mg maintenance dose; 7.2 mg is a labelled higher maintenance dose for weight. Oral forms (Rybelsus, Wegovy tablets) are taken daily on an empty stomach. With a one-week half-life, semaglutide stays in circulation 5 to 7 weeks after the last dose (Wegovy label).

Mechanism

Semaglutide binds and activates the GLP-1 receptor. It raises glucose-dependent insulin secretion, lowers glucagon, slows gastric emptying and reduces appetite and energy intake through central GLP-1 receptors (Wegovy label). It shares 94% sequence identity with human GLP-1. Aib at position 8 blocks DPP-4 degradation, Arg34 leaves one lysine for acylation, and a C18 fatty diacid with a hydrophilic spacer on Lys26 drives over 99% albumin binding, which slows clearance (Lau 2015; label). Direct vascular cardioprotection is proposed, not established.

Evidence

Clinical: at least one published human trial or an approved drug

STEP 1 (n=1961, 68 weeks): 2.4 mg weekly gave 14.9% weight loss versus 2.4% with placebo (Wilding et al., 2021)
STEP UP (n=1407, 72 weeks): 7.2 mg gave 18.7% weight loss versus 15.6% with 2.4 mg and 3.9% with placebo (Wharton et al., 2025)
SUSTAIN-6 (n=3297, type 2 diabetes): major cardiovascular events 6.6% versus 8.9%, hazard ratio 0.74 (Marso et al., 2016)
SELECT (n=17,604, obesity without diabetes): major cardiovascular events 6.5% versus 8.0%, hazard ratio 0.80 (Lincoff et al., 2023)
With cagrilintide (CagriSema, REDEFINE 1, n=3417): 20.4% weight loss at 68 weeks versus 3.0% with placebo (Garvey et al., 2025)
Status: FDA-approved and marketed. Ozempic (T2D, 2017), Rybelsus (oral, T2D, 2019), Wegovy (weight, 2021; CV risk 2024; MASH 2025; tablets 2025; 7.2 mg dose)

References

Side effects

Nausea, vomiting, diarrhea, and constipation are the most common effects and are usually worst during dose escalation. Serious risks include pancreatitis, gallbladder disease and gallstones, and delayed gastric emptying that raises aspiration risk under anesthesia. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2.

Storage

Storage: Refrigerated (2-8°C)
Lyophilized: 24+ months refrigerated
Reconstituted: 56 days refrigerated

Pharmacology

Half-life: ~1 week (subcutaneous, adults with overweight or obesity; present 5 to 7 weeks after last dose, Wegovy label)
Bioavailability: Subcutaneous 89% (Wegovy label); oral tablets reach much lower and more variable exposure (label)
Molecular weight: 4113.58 Da
Sequence: H[Aib]EGTFTSDVSSYLEGQAAK[spacer-C18 diacid]EFIAWLVRGRG

Stacks with

Cagrilintide