ATTAIN-1: Oral Orforglipron Reduced Weight in Obesity
ATTAIN-1 found that oral orforglipron 36 mg reduced body weight by 11.2% versus 2.1% with placebo over 72 weeks in adults with obesity without diabetes.
GLP-1 Receptor Agonists
Clinical trial summaries for GLP-1 receptor agonists, including cardiovascular outcomes, glycaemic control, obesity, kidney outcomes, tolerability, and practice implications.
STEP UP: Semaglutide 7.2 mg Delivered Additional Weight Loss in Obesity
In STEP UP, semaglutide 7.2 mg reduced body weight by 18.7% versus 3.9% with placebo and outperformed semaglutide 2.4 mg in adults with obesity without diabetes.
REDEFINE 1: CagriSema Produced 20.4% Weight Loss in Adults Without Diabetes
In REDEFINE 1, once-weekly cagrilintide-semaglutide produced 20.4% mean weight loss at 68 weeks versus 3.0% with placebo in adults with overweight or obesity without diabetes.
REDEFINE 2: CagriSema Reduced Weight and HbA1c in Type 2 Diabetes
In REDEFINE 2, CagriSema reduced weight by 13.7% versus 3.4% with placebo at 68 weeks, and 73.5% achieved HbA1c <=6.5% in adults with type 2 diabetes.
Do Conventional Risk Factor Changes Explain Exenatide’s Cardiovascular Effects? An EXSCEL Post Hoc Analysis
An EXSCEL post hoc simulation and mediation analysis showing conventional risk-factor changes explain only a modest share of once-weekly exenatide's cardiovascular effects. PICO summary and expert commentary.
Can a Ketogenic Diet Enhance the Effects of Dulaglutide in Type 2 Diabetes?
An RCT finds adding a ketogenic diet to dulaglutide improves glucose, lipids, and insulin resistance in type 2 diabetes. PICO summary and clinical expert commentary.
Is Once-Weekly Semaglutide Effective for Alcohol Use Disorder in Obese Patients?
A Lancet phase 2 RCT finds once-weekly semaglutide 2.4 mg reduces heavy drinking days in alcohol use disorder with obesity. PICO summary and expert commentary for clinicians.
SCALE: Liraglutide 3.0 mg for Obesity — The Trial That Opened the GLP-1 Weight Management Era
The SCALE trial established liraglutide 3.0 mg as the first GLP-1 receptor agonist approved for chronic weight management, demonstrating a mean weight reduction of 8.0% versus 2.6% with placebo and a 79% reduction in progression from prediabetes to type 2 diabetes in a 160-week extension analysis, setting the clinical and regulatory template for GLP-1 receptor agonist obesity pharmacotherapy.
SELECT: Semaglutide 2.4 mg Reduces Cardiovascular Events by 20% in Obese Non-Diabetic Patients with CVD
The SELECT trial demonstrated that semaglutide 2.4 mg reduces 3-point MACE by 20% in overweight or obese adults with pre-existing cardiovascular disease and no diabetes, becoming the first obesity pharmacotherapy trial to demonstrate a hard cardiovascular endpoint benefit and establishing GLP-1 receptor agonism as a cardiovascular intervention in non-diabetic obesity.
SURMOUNT-1: Tirzepatide Achieves up to 20.9% Weight Loss in Obesity — Entering Surgical Territory
SURMOUNT-1 demonstrated that tirzepatide, a dual GIP/GLP-1 receptor agonist, produces dose-dependent mean weight reductions of 15.0–20.9% in adults with obesity without type 2 diabetes, with 57% of participants at the 15 mg dose losing 20% or more of body weight, setting a new pharmacological efficacy benchmark comparable in magnitude to bariatric surgery outcomes.