The selection of therapeutics and trials discussed in this Commentary.
| Therapeutic | Study description | Ref. |
|---|---|---|
| CagriSema: a combination of cagrilintide (a long-acting, human amylin analogue) and semaglutide [a glucagon-like peptide-1 (GLP-1) receptor agonist] | REDEFINE-1: a 68-week efficacy and safety trial investigating CagriSema (a fixed dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg) compared to the individual components cagrilintide 2.4 mg, semaglutide 2.4 mg, and placebo, all administered s.c. once-weekly in 3,417 randomized adults with obesity or overweight (BMI of 27 kg/m2), NCT05567796.Primary end point: percentage of weight loss at week 68 with CagriSema versus placebo. | [3] |
| Retatrutide: an agonist of the glucose-dependent insulinotropic poly-peptide, glucagon-like peptide 1, and glucagon receptors | A 48-week phase 2 study in 338 adults with overweight or obesity (BMI 27 kg/m2) randomized to weekly s.c. retatrutide (1 mg, 4 mg, 8 mg, or 12 mg or placebo), NCT04881760.Primary end point: Percentage change in body weight from baseline to 24 weeks. | [4] |
| Semaglutide: a GLP-1 receptor agonist | SELECT: a cardiovascular (CV) outcome trial in 17,604 adults 45 years or older, with an initial BMI of 27 kg/m2 and established CV disease, randomized 1:1 to weekly s.c. semaglutide 2.4 mg or placebo, NCT03574597.Primary end point: a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. | [5] |
| High-dose semaglutide | STEP-UP: a 72-week efficacy and safety phase 3 trial investigating subcutaneous semaglutide 7.2 mg compared to semaglutide 2.4 mg and placebo, all administered once weekly in 1,407 randomized adults with obesity (BMI 30 kg/m2), NCT 05646706.Primary end point: percentage of weight loss at week 72 with semaglutide 7.2 mg versus placebo. | [10] |
| Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist | SURMOUNT-1: a phase 3 trial, in 2,539 overweight or obese adults randomized in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, NCT04184622.Coprimary end points: percentage change in weight from baseline and a weight reduction of 5% or more. | [9] |