Comparing Weekly GLP-1 Injections for Diabetes: Semaglutide Leads in Blood Sugar and Weight Reduction

Once-weekly GLP-1 receptor agonists effectively lower HbA1c and body weight in type 2 diabetes with a low risk of hypoglycemia. Semaglutide showed the greatest reductions in both HbA1c and body weight in head-to-head comparisons with exenatide ER and dulaglutide. Exenatide ER and dulaglutide demonstrated similar or superior efficacy to oral antidiabetic drugs. All once-weekly GLP-1 RAs were effective as both monotherapy and add-on therapy to various background medications including insulin. Gastrointestinal side effects (nausea, vomiting, diarrhea) were the most common adverse events.

This is a narrative review and supplement article synthesizing data from clinical trials of once-weekly GLP-1 receptor agonists including exenatide ER, dulaglutide, and semaglutide. It covers monotherapy data, head-to-head comparisons, add-on therapy with various background medications, and safety profiles.

The shift from daily to weekly injections was a major advance in GLP-1 peptide therapeutics, improving patient convenience and adherence. This review compares the three weekly GLP-1 RAs available at the time and highlights semaglutide's emerging superiority — foreshadowing its rise to become the most widely prescribed drug in this class. Understanding the comparative efficacy of these peptide drugs helps guide clinical decision-making.

This review captures the GLP-1 RA landscape just as semaglutide was establishing its clinical superiority, a trend that has since accelerated dramatically with approvals for obesity, cardiovascular risk reduction, and MASH. The comparative data reviewed here laid the groundwork for semaglutide's emergence as one of the most prescribed drugs in the world.

This supplement was funded by Novo Nordisk (semaglutide manufacturer), and most authors reported financial relationships with pharmaceutical companies. The review was published before the full scope of semaglutide's clinical program was complete, so longer-term and cardiovascular outcome data were not fully available. Head-to-head trial comparisons have limitations including different baseline patient characteristics.