​GLP-1 Clinical Trials: The Real Evidence Behind Every Medication

Petrelintide, a Roche and Zealand Pharma investigational drug, is a standalone amylin receptor agonist, distinct from GLP-1 medications, that produced 10.7% weight loss in the Phase 2 ZUPREME-1 trial, with Phase 3 announced in April 2026.

MariTide (maridebart cafraglutide), an Amgen investigational drug, combines GLP-1 receptor agonism with GIP receptor antagonism, the opposite of tirzepatide's approach, and produced up to 20% weight loss in a Phase 2 trial with once-monthly dosing, now advancing to Phase 3.

AWARD is the six-study Phase 3 program that established dulaglutide's original type 2 diabetes approval, with dulaglutide outperforming exenatide, insulin glargine, metformin, and sitagliptin in most head-to-head comparisons, and a related trial showing kidney-protective benefit in patients with chronic kidney disease.

SURMOUNT-4 directly tested what happens after stopping tirzepatide, finding participants who switched to placebo regained a mean of 14% of their body weight within a year, while those who continued treatment kept losing weight, the strongest direct evidence yet that GLP-1 medications require ongoing treatment to maintain results.

REWIND established Trulicity's cardiovascular risk reduction indication, enrolling 9,901 adults over a median follow-up of 5.4 years, the longest cardiovascular outcomes trial in the GLP-1 class, and notably the first with a majority of participants who had no prior cardiovascular disease.

PIONEER is the trial program that established oral semaglutide's evidence base, now used under the Ozempic tablet brand. PIONEER-6 confirmed cardiovascular safety, and real-world data supports oral semaglutide's superior blood sugar control compared to other diabetes medications.

LEADER established liraglutide's cardiovascular risk reduction indication, enrolling 9,340 adults with type 2 diabetes at high cardiovascular risk over a median follow-up of 3.8 years.

The SURMOUNT trial program established tirzepatide's efficacy for weight management, with SURMOUNT-1 showing up to 20.9% average weight loss, described by researchers as the strongest single result in obesity pharmacotherapy to date at the time of publication.

Amycretin, a Novo Nordisk investigational drug, is a single molecule combining GLP-1 and amylin receptor agonism, available in both oral and injectable formulations, with Phase 2 data showing roughly 14.5-15.2% weight loss, now advancing to Phase 3.

TRANSCEND-T2D-1 is retatrutide's first completed Phase 3 trial specifically in type 2 diabetes, showing meaningful A1C reduction alongside weight loss up to 16.8% at 40 weeks, complementing the obesity-focused TRIUMPH program.

ELIXA evaluated lixisenatide's cardiovascular safety in 6,068 adults with type 2 diabetes and a recent acute coronary event, demonstrating cardiovascular safety without showing a significant reduction in cardiovascular events.

TRIUMPH is the Phase 3 trial program for retatrutide, Eli Lilly's investigational triple agonist. TRIUMPH-1 showed up to 28.3% average weight loss at 80 weeks, among the highest reported for any obesity medication in development, with an NDA filing expected in late 2026.

SURPASS-2 was the first head-to-head trial comparing tirzepatide against injectable semaglutide specifically in type 2 diabetes, finding tirzepatide superior for both blood sugar control and weight loss, alongside a genuine tradeoff in discontinuation rates due to side effects.

FLOW is the trial that established semaglutide's kidney disease benefit in type 2 diabetes with chronic kidney disease, stopped early due to clear efficacy after showing a 24 percent reduction in major kidney disease events.

REDEFINE is the Phase 3 trial program for CagriSema, the investigational cagrilintide and semaglutide combination. REDEFINE 1 showed up to 22.7% average weight loss, and the program formed the basis of Novo Nordisk's December 2025 FDA submission.

The STEP trial program is the clinical trial series that established semaglutide's efficacy for weight management, with STEP 1 showing 14.9% average weight loss at 68 weeks and forming the basis for Wegovy's FDA approval.

Survodutide, a Boehringer Ingelheim and Zealand Pharma investigational drug, combines GLP-1 and glucagon receptor agonism and produced 16.6% weight reduction in the Phase 3 SYNCHRONIZE-1 trial, with a separate real focus on liver disease (MASLD).

DURATION is the trial program that established Bydureon's extended-release formulation as an improvement over twice-daily Byetta, showing greater A1C reduction with once-weekly dosing and similar weight loss.

SURMOUNT-2 tested tirzepatide specifically in adults with obesity and type 2 diabetes, showing meaningful but lower average weight loss, around 15.7%, than the non-diabetes SURMOUNT-1 population, an expected and well-documented pattern across GLP-1 weight trials.

EXSCEL evaluated extended-release exenatide's cardiovascular safety in 14,752 adults with type 2 diabetes, showing non-inferiority to placebo but not a statistically significant reduction in cardiovascular events, a more modest result than later GLP-1 trials.

SURMOUNT-OSA is the trial that established Zepbound's obstructive sleep apnea approval, two 52-week studies testing tirzepatide in adults with moderate-to-severe OSA and obesity, both with and without existing CPAP therapy.

SUSTAIN-6 established injectable semaglutide's cardiovascular risk reduction evidence in type 2 diabetes, enrolling 3,297 adults at high cardiovascular risk over a median follow-up of 2.1 years.

SELECT is the trial that established Wegovy's cardiovascular risk reduction approval, enrolling over 17,000 adults with established cardiovascular disease and showing a 20% reduction in major adverse cardiovascular events, independent of diabetes status.