Adherence, Persistence and Clinical Outcomes with Newer Glucose-Lowering Medications: A Systematic Review

Abstract

 Background: Newer glucose-lowering therapies, particularly sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists, provide substantial glycaemic, weight, cardiovascular and renal benefits. Their real-world effectiveness, however, depends on sustained treatment exposure. Methods: A systematic review was conducted according to PRISMA 2020 principles. MEDLINE/PubMed, Embase, Scopus, Web of Science and the Cochrane Library were searched from January 2015 through 30 June 2026. Adults with type 2 diabetes receiving SGLT2i, GLP-1 RA or dual GIP/GLP-1 RA therapy were eligible when studies reported persistence, adherence, discontinuation or related clinical outcomes. DPP-4 inhibitors were retained when used as active comparators. Because of substantial methodological heterogeneity, results were synthesized narratively. Results: A total of 2,177 records were identified. After removal of 521 duplicates, 1,656 records were screened and 1,458 were excluded. Of 198 reports sought for retrieval, 14 were unavailable; 184 full texts were assessed and 166 were excluded, leaving 18 studies for qualitative synthesis. One-year persistence commonly ranged from approximately 35% to 70%, with estimates influenced by medication class, dosing frequency, healthcare setting and permissible refill gap. Persistent/adherent patients generally achieved greater HbA1c reductions. Recent observational evidence also associated higher adherence with lower risks of hospitalization, cardiovascular or renal events and mortality. Once-weekly GLP-1 RA regimens generally demonstrated better persistence than daily injectable regimens, while comparative persistence between GLP-1 RAs and SGLT2i varied across healthcare systems. Conclusions: Treatment persistence with newer glucose-lowering therapies is suboptimal in routine practice and is clinically important. Greater persistence and adherence are consistently associated with improved glycaemic outcomes and increasingly with better cardiorenal outcomes. Treatment selection should integrate efficacy with tolerability, dosing frequency, treatment burden, affordability, access and patient preference.