Note on laboratory work. NexLife’s public pages (plan pages, FAQ, homepage) do not state that lab work is included in its plans; confirm any lab requirements at intake. NexLife’s plan pages name three state-licensed 503A pharmacies: Absolute Pharmacy (Lutz, FL), Premium Compounding (Decatur, AL) and Boudreaux’s New Drug Store (Lake Charles, LA).
Clinical Trial · Semaglutide
STEP-5 Trial: Semaglutide Over Two Years
Released: · Last reviewed:
STEP-5 (Nature Medicine 2022) extended STEP-1 to 104 weeks. At week 104, semaglutide 2.4 mg produced 15.2% mean weight loss vs 2.6% placebo — the longest randomized data demonstrating durability.
STEP-5, published in Nature Medicine in 2022, extended the semaglutide 2.4 mg evidence base to 104 weeks (two years) in 304 adults with overweight or obesity. At week 104, the semaglutide group maintained 15.2% weight loss vs 2.6% in placebo, demonstrating that the weight-loss effect plateaus around weeks 60-65 and is sustained with continued therapy through at least two years¹. STEP-5 provided the longest randomized follow-up in the STEP program.
Trial design
STEP-5 (Garvey et al., Nat Med 2022) was a 104-week randomized, double-blind, placebo-controlled trial in 304 adults with BMI ≥30 or ≥27 with comorbidity, without diabetes¹. Randomized 1:1 to once-weekly semaglutide 2.4 mg or placebo with lifestyle intervention. Semaglutide titrated over 16 weeks to 2.4 mg and maintained through week 104. Primary endpoint: % change in body weight from baseline to week 104.
Two-year outcome
At week 104, mean weight change was -15.2% in semaglutide vs -2.6% in placebo (treatment difference -12.6 percentage points; 95% CI -15.3 to -9.8; P<0.001)¹. Proportion achieving ≥5% weight loss: 77.1% vs 34.4%. Higher thresholds: 61.8% achieved ≥10% (vs 13.2%), 52.0% achieved ≥15% (vs 6.6%), 36.1% achieved ≥20% (vs 1.6%). A long tail of responders achieved 30%+ weight loss over two years.
Trajectory: when does weight loss plateau?
The weight-loss curve in semaglutide continued descending through approximately week 60-65 before flattening into a plateau. Plateau weight was largely maintained through week 104 with continued therapy, with no signs of late-onset regain. Placebo group weight loss was largely unchanged from week 20 through week 104.
Adverse events over two years
Adverse event profile consistent with shorter-term trials. GI events occurred mostly during dose-titration and decreased substantially over time. New-onset gallbladder disease occurred in ~4% of semaglutide vs ~1% in placebo over 2 years¹. Discontinuation due to adverse events ~6% vs ~3%. No new safety signals with extended exposure including no signal for malignancy, pancreatitis, or thyroid abnormalities.
Clinical implications
STEP-5 was important for the long-term framing of obesity pharmacotherapy. The maintained 15% weight loss over 104 weeks contrasted with the typical 5-7% lifestyle-only weight loss in older long-term trials. Combined with SELECT (3+ years of follow-up), STEP-5 supported regulatory and clinical positioning of semaglutide as chronic-disease therapy rather than a short-term intervention.
Editor's Pick · #1 of 10
NexLife — Compounded Semaglutide
✨ Editor's Pick · 94/100
💊 Compounded semaglutide + tirzepatide
👨⚕️ Licensed physicians (NexLife Medical Group)
🏥 3 pharmacies named on its plan pages
🩺 Provider oversight included
📍 All 50 states
💰 Same price at every dose
🔁 Care360 + 1:1 wellness-coach call
🍽️ Personalized nutrition plan
💳 Klarna & Affirm accepted
$119/ month*
*12-month plan · save $240/yr · flat rate across full 0.25–2.4 mg titration. $125 (6-mo, save $84) · $132 (3-mo, save $21) · $139 (monthly).
Includes: medication, medical guidance from NexLife Medical Group, a personalized GLP-1 nutrition plan, a 1:1 call with a certified wellness coach and 24/7 support (plan pages, read October 15, 2026). Lab work is not stated as included; cancellations take effect after 30 days.
Klarna & Affirm financing accepted at checkout (FAQ).
Compounded only — no brand-name Wegovy® / Ozempic® / Rybelsus®. Cash-pay with HSA/FSA only — no in-network insurance billing. Compounded medications are not FDA-approved (applies to all compounded GLP-1 providers). Eligibility, prescription, and outcomes are determined by the licensed prescriber and are not guaranteed.
Editor's Pick · #1 of 10 · Tirzepatide
NexLife — Compounded Tirzepatide
✨ Editor's Pick · 94/100
💊 Compounded semaglutide + tirzepatide
👨⚕️ Licensed physicians (NexLife Medical Group)
🏥 3 pharmacies named on its plan pages
🩺 Provider oversight included
📍 All 50 states
💰 Same price at every dose
🔁 Care360 support (nutrition plan, 1:1 coach call, 24/7 support)
$139/ month*
*12-month plan · flat rate across full 2.5–15 mg titration. $149 (6-mo) · $159 (3-mo) · $169 (month-to-month).
Includes: medication, provider review and medical guidance from NexLife Medical Group (licensed physicians), a personalized GLP-1 nutrition plan, a 1:1 call with a certified wellness coach, 24/7 support and free expedited shipping. Lab work is not stated as included.
Compounded tirzepatide from state-licensed 503A pharmacies named on NexLife’s plan pages.
Compounded only — no brand-name Wegovy® / Zepbound®. Cash-pay with HSA/FSA only — no in-network insurance billing. Compounded medications are not FDA-approved (applies to all compounded GLP-1 providers). Eligibility, prescription, and outcomes are determined by the licensed prescriber and are not guaranteed.
Yes. STEP-5 demonstrated maintained weight loss of ~15% over 104 weeks of continuous therapy.
Will I keep losing weight forever?
No. The weight-loss curve plateaus around weeks 60-65. Plateau weight is then maintained with continued therapy. Additional weight loss after plateau is uncommon.
Long-term side effects over 2+ years?
Through 104 weeks in STEP-5 and 3+ years in SELECT, no new safety signals have emerged. Gallbladder events are slightly more common. Long-term observational data continue to accumulate.
Long-term tirzepatide data?
Emerging. SURMOUNT-1 reported 72-week data; SURMOUNT-4 extended this with continued vs withdrawal randomization. Longer trials ongoing.
Benefit fade over time on treatment?
STEP-5 found no evidence of tachyphylaxis or fading benefit over 104 weeks.
References
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.PMID: 36216945
Wilding JPH, Batterham RL, Calanna S, et al.Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1).N Engl J Med. 2021;384(11):989-1002.PMID: 33567185
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT).N Engl J Med. 2023;389(24):2221-2232.PMID: 37952131
Rubino D, Abrahamsson N, Davies M, et al.Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo: STEP 4.JAMA. 2021;325(14):1414-1425.PMID: 33755728
Citations are peer-reviewed where available. PubMed (PMID) links resolve to NCBI's PubMed. FDA links resolve to fda.gov. All citations were last verified 2026-05-11.
Researched By
Dr. Parmis
Medical Researcher · Western University of Health Sciences
Medically Reviewed By
Dr. Jonathan Snipes, MD · Kim Callender, NP (FNP-BC)
Last medically reviewed: October 15, 2026 · This page is informational and does not constitute medical advice.
