20260615 Codex 產生 EBM 報告，例一
Semaglutide for Obesity: Evidence-Based Literature Review
Search date: June 15, 2026
Skill used: ebmsearch
Clinical Question
In people with obesity or overweight with weight-related comorbidity, how effective is semaglutide for weight reduction and weight maintenance versus placebo or other anti-obesity pharmacotherapy?
Search
Searched PubMed/MEDLINE via NCBI E-utilities, PubMed web records, and openFDA labeling.
Core query:
semaglutide AND (obesity OR overweight) AND (randomized OR trial OR systematic review OR meta-analysis OR STEP OR SELECT)
Priority was given to randomized controlled trials, systematic reviews/meta-analyses, and official labeling.
Bottom Line
High-certainty evidence supports semaglutide as an effective anti-obesity medication. In adults without diabetes, once-weekly subcutaneous semaglutide 2.4 mg plus lifestyle intervention produces about 12 percentage points greater weight loss than placebo at 68 to 104 weeks. Weight regain is common after discontinuation, so obesity should be treated as a chronic condition requiring ongoing management. Gastrointestinal adverse effects are common; gallbladder disease and discontinuation due to adverse events are clinically relevant.
Key Evidence
| Source | Population / Design | Main Findings | Limitations |
|---|---|---|---|
| STEP 1, NEJM 2021, PMID 33567185 | 1,961 adults, obesity/overweight, no diabetes; RCT, 68 weeks | Weight change: -14.9% semaglutide 2.4 mg vs -2.4% placebo; 15% weight loss achieved by 50.5% vs 4.9% | Sponsored by Novo Nordisk; trial population may not represent all real-world patients |
| STEP 2, Lancet 2021, PMID 33667417 | 1,210 adults with type 2 diabetes and overweight/obesity | -9.6% vs -3.4% placebo; effect smaller than in non-diabetes trials | Diabetes population; glycemic therapies may influence weight |
| STEP 3, JAMA 2021, PMID 33625476 | 611 adults without diabetes; semaglutide plus intensive behavioral therapy | -16.0% vs -5.7% placebo; 15% loss in 55.8% vs 13.2% | Intensive behavioral program may not be feasible in routine care |
| STEP 4, JAMA 2021, PMID 33755728 | Withdrawal trial after semaglutide run-in | Continued semaglutide: -7.9% from week 20 to 68; switched placebo: +6.9% regain | Enriched responders/tolerators before randomization |
| STEP 5, Nat Med 2022, PMID 36216945 | 304 adults, no diabetes; 104-week RCT | -15.2% vs -2.6% placebo at 2 years | Smaller sample; mostly female and White |
| STEP TEENS, NEJM 2022, PMID 36322838 | 201 adolescents with obesity | BMI change -16.1% vs +0.6%; 5% weight loss in 73% vs 18% | Pediatric long-term safety beyond trial duration remains important |
| Moiz meta-analysis, Am J Cardiol 2024, PMID 38679221 | 4 RCTs, 3,087 adults without diabetes | Relative weight WMD -12.1%; absolute WMD -12.3 kg; at least 20% loss in 33.4% vs 2.2% | Limited to RCTs available at that time |
| SELECT, NEJM 2023, PMID 37952131 | 17,604 adults, overweight/obesity, established cardiovascular disease, no diabetes | MACE 6.5% vs 8.0%; HR 0.80, 95% CI 0.72-0.90 | Cardiovascular-outcome population, not general obesity |
| STEP UP, Lancet Diabetes Endocrinol 2025, PMID 40961952 | Adults with obesity, no diabetes; 7.2 mg vs 2.4 mg vs placebo | 7.2 mg: -18.7%; 2.4 mg: -15.6%; placebo: -3.9% at 72 weeks | Newer higher-dose evidence; more GI events and dysesthesia |
Safety and Applicability
Adverse effects are mainly gastrointestinal and dose/titration related. In STEP 1, discontinuation due to gastrointestinal events was 4.5% vs 0.8% with placebo. In adolescents, cholelithiasis occurred in 4% on semaglutide vs 0% placebo.
The current openFDA Wegovy label lists a boxed warning for thyroid C-cell tumors and contraindication with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. The label also notes use with diet and physical activity and discourages combining Wegovy with other semaglutide or GLP-1 receptor agonist products.
Official label source: openFDA Wegovy label record
Clinical Takeaway
For eligible adults with obesity, or overweight plus weight-related comorbidity, semaglutide is among the most effective pharmacologic options for weight reduction. Expected average loss with 2.4 mg weekly is roughly 15% in non-diabetic adults and closer to 10% in type 2 diabetes populations. Benefits require ongoing treatment; stopping commonly leads to substantial regain.
Use should be individualized around contraindications, gastrointestinal tolerability, gallbladder and pancreatitis risk, pregnancy plans, diabetes therapies, access/cost, and long-term adherence.
References
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183. PMID: 33567185
- Davies M, Faerch L, Jeppesen OK, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2). Lancet. 2021;397(10278):971-984. doi:10.1016/S0140-6736(21)00213-0. PMID: 33667417
- Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight. JAMA. 2021;325(14):1403-1413. doi:10.1001/jama.2021.1831. PMID: 33625476
- Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224. PMID: 33755728
- Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083-2091. doi:10.1038/s41591-022-02026-4. PMID: 36216945
- Weghuber D, Barrett T, Barrientos-Perez M, et al. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022;387(24):2245-2257. doi:10.1056/NEJMoa2208601. PMID: 36322838
- Moiz A, Levett JY, Filion KB, Peri K, Reynier P, Eisenberg MJ. Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes. Am J Cardiol. 2024;222:121-130. doi:10.1016/j.amjcard.2024.04.041. PMID: 38679221
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563. PMID: 37952131
- Wharton S, Freitas P, Hjelmesaeth J, et al. Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP). Lancet Diabetes Endocrinol. 2025;13(11):949-963. doi:10.1016/S2213-8587(25)00226-8. PMID: 40961952
