The trials behind the prescriptions.
Plain-language syntheses of the pivotal phase-3 trials that established GLP-1 receptor agonist therapy in type 2 diabetes, obesity, cardiovascular risk reduction, and sleep apnea.
Tirzepatide for chronic weight management: SURMOUNT-1
Pivotal 72-week phase-3 RCT of tirzepatide in 2,539 adults with obesity. The 15 mg dose produced a mean total body weight reduction of 22.5%, and 36% of participants lost at least one quarter of their baseline body weight.
Semaglutide 2.4 mg for obesity: STEP-1
Pivotal phase-3 RCT of semaglutide 2.4 mg in 1,961 adults with obesity. Established the modern era of GLP-1 obesity pharmacotherapy and led to FDA approval of Wegovy in 2021.
Tirzepatide vs semaglutide in type 2 diabetes: SURPASS-2
Head-to-head 40-week trial of tirzepatide vs semaglutide in 1,879 adults with T2D. Tirzepatide 15 mg reduced HbA1c by 2.30 percentage points vs 1.86 for semaglutide 1 mg, and produced approximately twice the weight loss.
Semaglutide and cardiovascular outcomes: SELECT
Landmark CV outcomes trial of 17,604 adults establishing that semaglutide 2.4 mg reduces MACE in overweight/obese patients with pre-existing cardiovascular disease — independent of glycemic status.
Tirzepatide for OSA in adults with obesity: SURMOUNT-OSA
Two parallel 52-week phase-3 trials of tirzepatide in moderate-to-severe OSA: one without concurrent PAP therapy, one with. Both met their primary endpoints with substantial AHI reductions and adjunctive weight loss.
Continued vs withdrawn semaglutide for weight maintenance: STEP-4
Withdrawal trial demonstrating that GLP-1 obesity therapy must be continued long-term to maintain weight loss. Discontinuation at week 20 led to substantial regain over the following 48 weeks.
Semaglutide vs dulaglutide in T2D: SUSTAIN-7
Head-to-head trial of two once-weekly GLP-1 receptor agonists in T2D inadequately controlled on metformin. Semaglutide produced larger HbA1c and body-weight reductions at matched dose pairs.
Tirzepatide cardiovascular outcomes (SURPASS-CVOT)
Active-comparator CV outcomes trial of tirzepatide vs dulaglutide in 13,299 adults with T2D and established CVD or high CV risk. Headline non-inferiority was met; superiority signals are being analyzed by indication subgroup.
Semaglutide and cardiovascular outcomes in T2D: SUSTAIN-6
Original CV outcomes trial establishing the CV benefit of semaglutide in T2D. Underpinned the early indication-creep of GLP-1 receptor agonists from glycemic to cardiometabolic therapy.
Continued vs withdrawn tirzepatide: SURMOUNT-4
Tirzepatide counterpart to STEP-4. Reinforces that GLP-1/GIP obesity therapy is chronic — discontinuation results in regain.