Can once-weekly semaglutide produce meaningful weight loss in adults with obesity?

In this 2-minute evidence brief, we break down the STEP 1 trial, a randomized double-blind clinical trial published in the New England Journal of Medicine in 2021. The study tested semaglutide 2.4 mg once weekly versus placebo, both with lifestyle intervention, in adults with overweight or obesity but without diabetes.

Covered in this video:

• Why the STEP 1 trial was done
• How the trial was conducted
• Main weight loss results
• Safety and gastrointestinal side effects
• Key clinical takeaway
• 
  

Main result: average body weight decreased by 14.9% with semaglutide versus 2.4% with placebo over 68 weeks.

Citation:

Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021.

PMID: 33567185

DOI: 10.1056/NEJMoa2032183

This video is for medical education only and does not replace clinical judgment or individual medical advice.

#Semaglutide #STEP1Trial #ObesityMedicine #GLP1 #MedicalEducation

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This week on Hormone Insight: the fallout from the ADA 2026 Scientific Sessions, where retatrutide — a triple GIP/GLP-1/glucagon agonist — delivered nearly 2 points of A1C and about 15% weight loss in type 2 diabetes (TRANSCEND-T2D-1). Plus CagriSema vs semaglutide head-to-head, finerenone in chronic kidney disease without diabetes, the new ADA/EASD type 1 diabetes consensus, and a Hormone Classic revisit of SUSTAIN-6 — the outcome bar every new drug still has to clear.

Segments:

• Trial of the Week — Retatrutide in type 2 diabetes (TRANSCEND-T2D-1, The Lancet)

• Quick Hit 1 — CagriSema vs semaglutide (REIMAGINE 2, Lancet Diabetes & Endocrinology)

• Quick Hit 2 — Finerenone in CKD without diabetes (FIND-CKD, NEJM)

• Guideline & FDA Watch — ADA/EASD type 1 diabetes in adults: 2026 consensus update

• Hormone Classic — SUSTAIN-6 (semaglutide cardiovascular outcomes, 2016)

⏱ Chapters

00:00 Cold open

00:38 Welcome & disclaimer

01:02 This week

01:47 Trial of the Week — Retatrutide (TRANSCEND-T2D-1)

03:51 The Appraisal

04:59 Bottom line — retatrutide

05:29 Quick Hit 1 — CagriSema vs semaglutide

06:54 Quick Hit 2 — Finerenone in CKD without diabetes

08:04 Guideline & FDA Watch — ADA/EASD type 1 diabetes

09:20 Hormone Classic — SUSTAIN-6

10:40 The Bottom Line

11:23 Sign-off

References & written summary: hormoneinsight.com/twide-2026-06-27

For healthcare professionals. Educational, not individual medical advice.

Subscribe for a new episode every Saturday. #diabetes #endocrinology #GLP1

This week on This Week in Diabetes & Endocrinology, from Hormone Insight: the

first large phase 3 trial of an oral GLP-1, orforglipron, in adults with type 2

diabetes and obesity (ATTAIN-2, Lancet). The headline is not the size of the

weight loss. It is the word oral.

Also this week:

- A 112,000-patient ACP network meta-analysis that keeps semaglutide and

tirzepatide on top for both weight loss and cardiovascular outcomes

- A provocative real-world comparison of bariatric surgery versus semaglutide

in fatty liver disease

- The 2026 ADA Standards of Care, which make cardiovascular and kidney

protection a co-primary goal alongside A1C

- A Hormone Classic revisit of UKPDS that explains why that shift had to happen

One question runs through all of it: does this change Monday clinic?

Chapters

00:00 Cold open

00:42 This week

01:13 Trial of the Week: orforglipron (ATTAIN-2)

04:29 Quick Hit: ACP weight-loss drug meta-analysis

05:21 Quick Hit: surgery vs semaglutide (MASLD)

06:21 Guideline & FDA Watch: 2026 ADA Standards

07:27 Hormone Classics: UKPDS

08:26 The Bottom Line

08:57 Sign-off

References and written summary: hormoneinsight.com/[slug]

For healthcare professionals. Educational, not individual medical advice.

Subscribe for a new episode every Saturday.

#diabetes #endocrinology #GLP1 #obesity #ADA2026