Medical Researcher · Western University of Health Sciences
Medically Reviewed By
Dr. Jonathan Snipes, MD · Kim Callender, NP (FNP-BC)
Last medically reviewed: June 1, 2026 · This page is informational and does not constitute medical advice.
STEP-2 (Lancet 2021) tested semaglutide 2.4 mg in 1,210 adults with T2D and overweight or obesity. Mean weight loss was 9.6% versus 3.4% placebo at 68 weeks, with HbA1c reduction of 1.6 percentage points.
Clinical reference4 peer-reviewed sources
Editorial summary
STEP-2, published in The Lancet in 2021, tested once-weekly semaglutide 2.4 mg versus 1.0 mg and placebo in 1,210 adults with T2D and overweight or obesity. At 68 weeks, the 2.4 mg group achieved 9.6% mean weight loss versus 3.4% with placebo, with HbA1c reduction of ~1.6 percentage points versus 0.4¹. STEP-2 established that semaglutide 2.4 mg provides clinically meaningful weight loss and glycemic improvement in T2D, though weight-loss magnitude is approximately one-third less than STEP-1 (non-diabetic).
Trial design
STEP-2 (Davies et al., Lancet 2021) was a 68-week randomized, double-blind, placebo-controlled trial in 1,210 adults with T2D, BMI ≥27, HbA1c 7-10%, on stable background therapy or diet alone¹. Randomized 1:1:1 to once-weekly subcutaneous semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo, all with lifestyle counseling. Semaglutide titrated over 16 weeks. Co-primary endpoints: % change in body weight and proportion achieving ≥5% weight loss at week 68.
Weight loss outcomes
At week 68, mean weight change was -9.6% in 2.4 mg, -7.0% in 1.0 mg, and -3.4% placebo (treatment difference 2.4 mg vs placebo -6.2 percentage points; 95% CI -7.3 to -5.2; P<0.001)¹. Proportion achieving ≥5% weight loss: 68.8%, 57.1%, 28.5%. Higher thresholds at the 2.4 mg dose: 45.6% achieved ≥10% loss, 25.8% achieved ≥15% loss.
Glycemic outcomes
HbA1c reduction was substantial across both semaglutide doses: -1.6 percentage points in 2.4 mg arm and -1.5 in 1.0 mg arm vs -0.4 in placebo (P<0.001 for both vs placebo)¹. Proportion achieving HbA1c <7.0%: 67.5%, 65.6%, 15.7%. The additional weight loss with 2.4 mg did not translate into substantially greater HbA1c reduction over 1.0 mg, suggesting glycemic effect plateaus near the 1.0 mg dose used in Ozempic for T2D.
Why diabetic patients lose less weight
STEP-1 (non-diabetic) showed 14.9% weight loss vs 9.6% in STEP-2 (diabetic) at the same 2.4 mg dose. The approximately one-third reduction in T2D has been observed consistently across the GLP-1 RA class and is incompletely understood². Hypothesized mechanisms: lower baseline ghrelin sensitivity, concurrent insulin or sulfonylurea therapy that promotes weight retention, metabolic differences in fuel partitioning. Patients with T2D should be counseled to expect 7-10% mean weight loss on semaglutide 2.4 mg rather than the 14-15% headline figures from STEP-1.
Safety profile
Adverse events similar to STEP-1, dominated by GI symptoms primarily during dose escalation. Discontinuation due to adverse events ~7% in 2.4 mg vs ~3% in placebo¹. Hypoglycemia rates low overall (~3% in semaglutide vs ~1% in placebo). Higher rates with background sulfonylureas; preemptive sulfonylurea dose reduction is standard practice.
$99 on 6 months · $105 on 3 months · $109 month to month. The same price at every dose and no membership fee (nexlife.us plan page, read November 6, 2026).
Included in the price: the medication, medical guidance from NexLife Medical Group, a GLP-1 nutrition plan, a 1:1 call with a certified wellness coach, 24/7 support and free expedited shipping. Lab work is not listed as included.
Pharmacies named on its plan pages:Absolute Pharmacy (Lutz, FL), Premium Compounding (Decatur, AL) and Boudreaux’s New Drug Store (Lake Charles, LA), described as state-licensed 503A compounding pharmacies.
Trade-offs: compounded semaglutide is not FDA-approved and is not Wegovy or Ozempic. Cash pay only (FSA/HSA cards accepted for eligible portions). Cancellations take effect after 30 days, so one more shipment may be charged. A prescription depends on a licensed clinician’s review.
$119 on 6 months · $125 on 3 months · $129 month to month. The same price at every dose and no membership fee (nexlife.us plan page, read November 6, 2026).
Included in the price: the medication, medical guidance from NexLife Medical Group, a GLP-1 nutrition plan, a 1:1 call with a certified wellness coach, 24/7 support and free expedited shipping. Lab work is not listed as included.
Pharmacies named on its plan pages:Absolute Pharmacy (Lutz, FL), Premium Compounding (Decatur, AL) and Boudreaux’s New Drug Store (Lake Charles, LA), described as state-licensed 503A compounding pharmacies.
Trade-offs: compounded tirzepatide is not FDA-approved and is not Zepbound or Mounjaro. Cash pay only (FSA/HSA cards accepted for eligible portions). Cancellations take effect after 30 days, so one more shipment may be charged. A prescription depends on a licensed clinician’s review.
STEP-2: mean weight loss on semaglutide 2.4 mg was 9.6% at 68 weeks — approximately one-third less than non-diabetic patients on the same dose.
Ozempic or Wegovy for T2D + weight management?
Ozempic is FDA-approved for T2D at doses up to 2.0 mg. Wegovy is approved for chronic weight management at 2.4 mg. Patients with both may use either; insurance often drives the decision.
Does semaglutide work for diabetes if I'm not overweight?
Ozempic is FDA-approved for T2D regardless of weight. Wegovy 2.4 mg requires BMI ≥27 with comorbidity or ≥30.
How much will A1c drop on Ozempic?
~1.5-1.6 percentage points at 1.0 mg or 2.4 mg weekly in patients with baseline HbA1c 7-10%.
Hypoglycemia risk on semaglutide?
Semaglutide alone rarely causes hypoglycemia. Risk rises substantially when combined with insulin or sulfonylureas — preemptive dose reduction of those medications is standard.
References
Davies M, Færch 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.PMID: 33667417
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
Marso SP, Bain SC, Consoli A, et al.Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6).N Engl J Med. 2016;375(19):1834-1844.PMID: 27633186
U.S. Food and Drug Administration.Ozempic (semaglutide) injection — Prescribing Information.FDA Drug Approval Records.View source
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.