Reduces appetite via hypothalamic signaling, slows gastric emptying, improves pancreatic beta-cell function and insulin sensitivity. Anti-inflammatory and cardiovascular protective effects.
T2D management, chronic weight management (BMI 30+ or 27+ with comorbidity), MACE risk reduction in cardiovascular disease.
Personal/family history of medullary thyroid carcinoma (MTC), MEN2, pancreatitis history, severe GI disease, pregnancy/lactation, diabetic retinopathy.
FDA-approved 2017 (T2D), 2021 (obesity). Landmark STEP trials and SELECT cardiovascular outcomes trial.
- 1.Wilding JPH et al., NEJM 2021 (STEP 1) — 14.9% mean weight loss vs 2.4% placebo. n=1,961, Phase III RCT
- 2.Lincoff AM et al., NEJM 2023 (SELECT) — 20% MACE reduction, first obesity medication with CV benefit independent of glycemic control. n=17,604
- 3.Davies M et al., Lancet 2021 (STEP 2) — 9.6% weight loss in T2DM patients. n=1,210
- 4.Rubino D et al., JAMA 2021 (STEP 4) — two-thirds weight regain after discontinuation. n=803
- 5.SHAPE Real-World, PMC 2025 — 14.1% mean weight loss at 1 year. n=9,916
Weight regain after discontinuation is substantial (STEP 4). Muscle mass loss concerns. GI side effects common (nausea 44%). Cost/access barriers ($1,000+/month without insurance).
Oral semaglutide higher-dose formulations. Alzheimer's disease trials (EVOKE). NASH/MAFLD applications. Addiction behavior research.