Semaglutide

Ozempic · Wegovy · Rybelsus

FDA-approved (T2D, obesity) Cardio-protective (SELECT) Reno-protective (FLOW) Off-label microdosing exists Black-box: medullary thyroid carcinoma

A long-acting glucagon-like peptide-1 receptor agonist, modified for albumin binding to extend half-life to once-weekly subcutaneous dosing (or daily oral, with a stricter fasted-window protocol). The first GLP-1 agent with hard-endpoint cardiovascular and renal trial readouts in obesity and CKD populations.

Semaglutide injection pen — Ozempic Wegovy Rybelsus GLP-1 receptor agonist for type 2 diabetes and obesity

Class

GLP-1 RA

Half-life

~165 hours

Route

SC weekly / PO daily

Trials

STEP, SELECT, FLOW

01 / Mechanism

What it actually does.

Semaglutide is a synthetic peptide analog of human GLP-1 with two modifications: an Aib (α-aminoisobutyric acid) substitution at position 8 that resists DPP-4 degradation, and a C18 fatty-acid side chain at position 26 that promotes reversible albumin binding [Lau 2015]. The result is a peptide with a ~165-hour half-life — practical for weekly dosing — that retains agonist activity at the GLP-1 receptor.

At the receptor, semaglutide drives the same downstream cascade as native GLP-1: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, central satiety signaling, and a tissue distribution that explains the cardiovascular and renal outcomes. See the long read on the GLP-1 era for the full pharmacology.

02 / Dosing

Standard titration schedule.

Week	Subcutaneous dose	Indication	Note
1–4	0.25 mg weekly	Initiation	Not therapeutic — tolerance dose
5–8	0.5 mg weekly	Type 2 diabetes (low)	First step with glycemic effect
9–12	1.0 mg weekly	T2D maintenance	Most patients can hold here
13–16	1.7 mg weekly	Obesity titration	Wegovy stepping dose
17+	2.4 mg weekly	Obesity maintenance	STEP trial target

Slower if needed

The trial titration is conservative for a reason. Side effects are dose-dependent and tachyphylactic — they ease with time. Holding a dose for 6–8 weeks (instead of 4) before stepping is common in clinical practice for GI-sensitive patients.

Reconstitution math

For a compounded 5 mg vial reconstituted with 2 mL bacteriostatic water, a 0.25 mg starting dose draws to 10 units on a U-100 insulin syringe. Use the reconstitution calculator for any other combination of vial size, BAC volume, and target dose.

03 / Contraindications

Who should not take this.

Personal or family history of medullary thyroid carcinoma (MTC). FDA black-box warning, based on rodent C-cell hyperplasia data — debated clinical relevance, but the contraindication stands.
Multiple endocrine neoplasia syndrome type 2 (MEN 2). Same rationale.
Prior pancreatitis. Relative contraindication; pancreatitis is a labelled adverse event though absolute risk is low.
Severe gastroparesis. Drug exacerbates the underlying motility problem.
Pregnancy or planned pregnancy within 2 months. Long half-life — wash out before conception.
Active gallbladder disease. Cholelithiasis risk increases with rapid weight loss.

04 / Side effects

What to expect.

Nausea (~44% at initiation). Almost always tachyphylactic. Worst at dose escalations. Mitigations: smaller meals, lower protein at first bite, anti-emetic if persistent.
Constipation (~24%). Magnesium citrate, hydration, fiber. Persists more than nausea.
Diarrhea (~30%). Usually transient. If it persists past week 4 at a stable dose, consider intolerance.
Fatigue, "ozempic face". Largely a function of rapid weight loss rather than the drug itself. Slow the titration; protect lean mass.
Loss of muscle mass (~25–40% of total lost). Mitigated by ≥1.6 g/kg protein and resistance training.
Rare: pancreatitis, gallbladder disease, retinopathy progression in pre-existing diabetic retinopathy.

05 / Cost

Honest pricing.

Source	Form	~Monthly cost (USD)	Note
Brand	Wegovy pen (insurance covered)	$25–$50 copay	If covered
Brand	Wegovy pen (cash)	$1,300+	List price
Brand	Ozempic pen (cash)	$950+	T2D label only
Compounded	503A pharmacy vial	$250–$450	Regulatory ambiguity
Compounded	503B (during shortage)	$180–$300	Shortage-dependent

Compounding caveat

FDA removed semaglutide from the drug-shortage list in early 2025, narrowing the window for 503A and 503B compounding under shortage rules. The legal status of personalized compounded GLP-1s remains evolving — see the latest regulatory update.

06 / Key trials

The evidence base.

STEP 1 — Semaglutide 2.4 mg vs. placebo in obesity (no T2D), 68 weeks. −14.9% weight. [Wilding 2021, NEJM]
STEP 4 — Continued vs. withdrawn semaglutide. Weight regain on withdrawal — drug works while taken. [Rubino 2021, JAMA]
SUSTAIN-6 — Cardiovascular outcomes in T2D, 2.4 years. 26% reduction in MACE. [Marso 2016, NEJM]
SELECT — Non-diabetic obesity + prior CV disease, ~40 months. 20% MACE reduction, HR 0.80. [Lincoff 2023, NEJM]
FLOW — T2D + CKD. Stopped early for benefit. 24% reduction in primary renal composite. [Perkovic 2024, NEJM]

About this profile

Last reviewed against evidence: 2026-05-11. This profile is editorial reference content, not sponsored. Where Wellness Radar publishes sponsored content or affiliate links, they are clearly labeled. Educational reference, not a prescription — decisions about semaglutide belong to you and a clinician who knows your full medical history.