What the Semaglutide Studies Found

Semaglutide has been tested in tens of thousands of people. This page picks out the studies that shaped its use and groups them by question. Numbers are rounded; the full references are listed at the bottom.

Blood Sugar: the SUSTAIN Studies

• SUSTAIN 1 (Lancet Diabetes & Endocrinology, 2017): in 388 adults with type 2 diabetes who took no other diabetes medicine, HbA1c fell by about 1.5 percentage points after 30 weeks on semaglutide, while it barely changed on placebo.
• SUSTAIN 7 (Lancet Diabetes & Endocrinology, 2018): in 1,201 adults, semaglutide was compared directly with dulaglutide, another weekly GLP-1 drug. At the higher doses HbA1c fell by 1.8 points against 1.4, and body weight by 6.5 kg against 3.0 kg.

Heart Safety in Diabetes: SUSTAIN 6 and PIONEER 6

Regulators require new diabetes drugs to show that they do not raise cardiovascular risk. In SUSTAIN 6 (NEJM, 2016), 3,297 people at high risk were followed for two years. Heart attack, stroke or cardiovascular death occurred in 6.6% on semaglutide and 8.9% on placebo. The study also found more complications of diabetic eye disease (retinopathy) with semaglutide, a finding that is still watched closely. PIONEER 6 (NEJM, 2019) confirmed that the tablet form did not increase heart risk in 3,183 people.

Weight: the STEP Studies

• STEP 1 (NEJM, 2021): 1,961 adults with obesity, or with overweight and a related condition, took semaglutide 2.4 mg or placebo alongside lifestyle advice. After 68 weeks the average weight loss was 14.9% against 2.4%. Half of those on semaglutide lost at least 15% of their weight.
• STEP 4 (JAMA, 2021): everyone first took semaglutide for 20 weeks and lost about 10.6% of their weight. Those who stayed on it lost another 7.9% by week 68, while those switched to placebo regained 6.9%.
• STEP 1 extension (Diabetes, Obesity and Metabolism, 2022): one year after stopping, participants had regained around two-thirds of the weight they had lost, and improvements in blood pressure and blood fats mostly faded.
• STEP TEENS (NEJM, 2022): in 201 adolescents aged 12 to 17, body mass index fell by 16.1% with semaglutide and rose by 0.6% with placebo over 68 weeks.

Heart Outcomes Without Diabetes: SELECT

SELECT (NEJM, 2023) was the first large outcomes trial of a weight-management medicine in people without diabetes. It enrolled 17,604 adults with existing cardiovascular disease and overweight or obesity and followed them for about three years. Heart attack, stroke or cardiovascular death occurred in 6.5% on semaglutide and 8.0% on placebo, a 20% lower relative risk. Side effects led 16.6% of those on semaglutide to stop treatment, compared with 8.2% on placebo.

Kidneys, Heart Failure and Liver

• Chronic kidney disease (FLOW, NEJM, 2024): in 3,533 people with type 2 diabetes and kidney disease, semaglutide lowered the risk of kidney failure, a large drop in kidney function, or death from kidney or heart causes by 24%. The trial was stopped early because the benefit was clear.
• Heart failure (STEP-HFpEF, NEJM, 2023): in 529 people with obesity and heart failure with preserved ejection fraction, symptom and activity scores improved by 16.6 points with semaglutide against 8.7 with placebo, and six-minute walking distance also improved.
• Fatty liver disease (ESSENCE, NEJM, 2025): in 800 people with MASH and liver scarring, the liver inflammation resolved without worse scarring in 62.9% on semaglutide and 34.3% on placebo after 72 weeks. Scarring improved in 36.8% against 22.4%. A 2021 Phase 2 trial had pointed the same way.

Unanswered Questions

• How best to keep weight off after stopping, given how much is regained.
• How much lean tissue and muscle is lost along with fat, and whether it matters for older adults.
• What the eye findings mean over many years, including rare optic nerve problems reported since approval.
• Which of the many conditions now being studied will benefit. In November 2025, for example, Novo Nordisk announced that two large trials of the tablet in early Alzheimer's disease did not slow the disease.