Semaglutide Research: STEP, SELECT, FLOW & SUSTAIN Trial Data
A trial-by-trial look at the major Semaglutide clinical programmes — STEP, SELECT, FLOW and SUSTAIN — with headline numbers, study designs and source links.
Mechanism of action
Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist. It mimics the natural GLP-1 peptide but is modified with a specialised linker and a C18 di-acid chain that slows clearance, extending its half-life in humans to roughly one week and allowing once-weekly dosing.
By activating GLP-1 receptors in the pancreas, brain and gut, semaglutide enhances glucose-dependent insulin secretion, suppresses glucagon release, delays gastric emptying and targets hypothalamic appetite circuits. The result is improved glycaemic control, reduced food cravings and increased satiety.
Large-scale human programmes — STEP, SUSTAIN, SELECT and FLOW — have investigated whether these mechanisms translate into measurable outcomes for weight, cardiovascular risk, renal function and metabolic health.
The studies
The semaglutide evidence base rests on four large published trial programmes. Each card below states the primary objective, the design, the headline result and links to the original publication or registry record.
STEP programme
STEP-1 — obesity and weight management
To evaluate the efficacy and safety of once-weekly 2.4 mg subcutaneous semaglutide for chronic weight management in adults with overweight or obesity.
1,961 adults with overweight or obesity · 68 weeks · randomised, double-blind, placebo-controlled
- 14.9%
- Mean weight loss (semaglutide)
- 86.4%
- Participants losing ≥ 10% body weight
- 69.2%
- Participants losing ≥ 20% body weight
vs 2.4% placebo
vs 31.5% placebo
vs 11.8% placebo
- STEP-1 established the weight-loss ceiling for once-weekly 2.4 mg semaglutide in a non-diabetic population.
- The effect was dose-dependent and appeared early, with continued separation from placebo throughout the 68-week period.
- Improvements in cardiometabolic risk factors — waist circumference, blood pressure and lipid profiles — tracked with the degree of weight loss.
SELECT programme
SELECT — cardiovascular outcomes
To determine whether once-weekly 2.4 mg semaglutide reduces cardiovascular risk in people with pre-existing cardiovascular disease and obesity, without diabetes.
17,604 adults with overweight/obesity and established CVD · median follow-up ~40 months · randomised, double-blind, placebo-controlled
- 20%
- Relative reduction in MACE
- Reduced
- Cardiovascular death
- Reduced
- All-cause mortality
vs placebo
- SELECT was the first outcome trial to show that a GLP-1 receptor agonist at a weight-management dose reduces major adverse cardiovascular events in a non-diabetic population.
- The benefit was consistent across the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke.
- The result shifted semaglutide from a metabolic agent to a cardiovascular-risk modifying therapy in obesity.
FLOW programme
FLOW — chronic kidney disease outcomes
To assess the impact of once-weekly 1.0 mg semaglutide on the progression of chronic kidney disease in patients with type 2 diabetes.
3,533 adults with type 2 diabetes and CKD · randomised, double-blind, placebo-controlled · stopped early for efficacy
- 24%
- Reduction in primary kidney events
- 24%
- Reduction in kidney failure
- 20%
- Lower all-cause mortality
vs placebo
vs placebo
vs placebo
- FLOW was stopped early because the prespecified interim analysis showed clear benefit on kidney outcomes.
- Semaglutide reduced the risk of the composite kidney endpoint — including kidney failure and death from kidney causes — by 24%.
- The 20% reduction in all-cause mortality was an unexpected and clinically important secondary signal.
SUSTAIN programme
SUSTAIN-6 — type 2 diabetes and cardiovascular safety
To evaluate the long-term glycaemic control and cardiovascular safety of semaglutide versus standard diabetes therapies in patients with type 2 diabetes.
3,297 adults with type 2 diabetes at high CV risk · 104 weeks · randomised, double-blind, placebo-controlled
- 26%
- Relative reduction in CV death, stroke or MI
- 1.8%
- HbA1c reduction
- 6.5%
- Body weight reduction
vs placebo
vs baseline
vs baseline
- SUSTAIN-6 was the first major signal that semaglutide improves cardiovascular outcomes in type 2 diabetes, not merely glucose.
- The trial also demonstrated sustained HbA1c lowering and meaningful weight reduction over two years.
- Retinopathy events were slightly increased in the semaglutide arm, prompting ongoing vigilance in eye screening during initiation.
Storage & handling
Semaglutide research material is supplied as a lyophilised powder. Store sealed vials refrigerated or frozen, protected from light and moisture.
Reconstitute with bacteriostatic water added slowly down the inner wall of the vial; swirl gently until dissolved — do not shake.
Keep reconstituted solution at 2-8 °C and use within the stability window defined by your lab's standard operating procedures. Avoid repeated freeze-thaw cycles.
All information on this page is provided for laboratory and educational reference only. Peptides Lab SA (PTY) Ltd supplies compounds strictly for in-vitro research use. Nothing here is medical advice, a dosing recommendation, or a claim of human safety or efficacy.