Daily Endocrinology Research Analysis
Two phase 3 randomized trials in The Lancet show that once-weekly insulin efsitora alfa achieves non-inferior glycemic control compared with daily basal insulins (degludec and glargine U100), with a substantial reduction in injection frequency. A large real-world Diabetes Care study further suggests that initiating GLP-1 receptor agonists versus DPP-4 inhibitors in chronic kidney disease is associated with fewer emergency visits and hospitalizations.
Summary
Two phase 3 randomized trials in The Lancet show that once-weekly insulin efsitora alfa achieves non-inferior glycemic control compared with daily basal insulins (degludec and glargine U100), with a substantial reduction in injection frequency. A large real-world Diabetes Care study further suggests that initiating GLP-1 receptor agonists versus DPP-4 inhibitors in chronic kidney disease is associated with fewer emergency visits and hospitalizations.
Research Themes
- Once-weekly basal insulin as a treatment innovation
- Comparative effectiveness of incretin therapies in CKD
- Reducing treatment burden while maintaining glycemic control
Selected Articles
1. Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial.
In this 78-week, multicenter, phase 3, treat-to-target non-inferiority RCT, once-weekly efsitora achieved non-inferior glycemic control to daily degludec in adults with type 2 diabetes on basal insulin. Efsitora was well tolerated and offers a marked reduction in injection frequency.
Impact: This trial introduces a once-weekly basal insulin as a viable alternative to daily regimens, potentially improving adherence and patient experience without sacrificing glycemic outcomes.
Clinical Implications: Efsitora can be considered for adults with T2D requiring basal insulin, especially those struggling with daily injections; real-world studies should assess adherence, quality-of-life, and long‑term safety.
Key Findings
- Once-weekly efsitora was non-inferior to once-daily degludec for HbA1c control over 78 weeks.
- The study supports efsitora as a well-tolerated weekly basal insulin option.
- Injection frequency is substantially reduced with weekly dosing, potentially improving adherence.
Methodological Strengths
- Phase 3, randomized, treat-to-target non-inferiority design over 78 weeks
- Large, multinational, multicenter enrollment
Limitations
- Open-label design may introduce performance and detection bias
- Generalizability limited to adults on basal insulin without prandial insulin
Future Directions: Evaluate real-world effectiveness, adherence, quality-of-life, hypoglycemia profiles, and outcomes in special populations (older adults, CKD, hepatic impairment).
2. Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial.
In adults with type 2 diabetes already using basal–bolus therapy, once-weekly efsitora was non-inferior to daily glargine U100 for HbA1c control over 26 weeks in a phase 3 treat-to-target trial. The weekly regimen offers reduced injection burden without compromising efficacy.
Impact: Extends weekly basal insulin evidence to the complex basal–bolus population, addressing a high-burden regimen where reducing injection frequency could meaningfully improve adherence.
Clinical Implications: Weekly basal insulin may be considered in basal–bolus users to reduce burden; clinicians should monitor for glycemic targets and individualize prandial dosing alongside the weekly basal strategy.
Key Findings
- Once-weekly efsitora was non-inferior to daily glargine U100 for HbA1c change at 26 weeks.
- Trial included adults on basal–bolus regimens across multiple countries and sites.
- Weekly dosing offers potential adherence and satisfaction benefits in high-burden regimens.
Methodological Strengths
- Phase 3 randomized treat-to-target non-inferiority design
- International, multicenter enrollment with standardized titration
Limitations
- Open-label design with potential bias
- 26-week duration limits longer-term safety and durability assessments
Future Directions: Assess long-term durability, hypoglycemia patterns, patient-reported outcomes, and economic impact of weekly basal insulin in basal–bolus users.
3. Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Emergency Department Visits and Hospitalization in Patients With Chronic Kidney Disease.
In >48,000 adults with impaired kidney function, initiating GLP-1RA versus DPP-4i was associated with a 10% relative reduction in the risk of all-cause ED encounters or hospitalizations, robust across recurrent event models. Findings support broader use of GLP-1RA in CKD for overall acute care reduction.
Impact: Provides large-scale comparative effectiveness data linking GLP-1RA initiation to fewer acute care encounters across CKD stages, informing therapy selection beyond glycemic endpoints.
Clinical Implications: When choosing incretin therapy in CKD, GLP-1RA may be preferred over DPP-4i to reduce ED visits/hospitalizations, while individualizing based on tolerability, cardiovascular/renal profiles, and access.
Key Findings
- GLP-1RA initiation was associated with lower risk of all-cause ED encounters or hospitalizations vs DPP-4i (HR 0.90; 95% CI 0.87–0.94).
- Results were consistent using multiple recurrent event models (PWP gap-time, Andersen–Gill, PWP calendar time).
- Effect observed across the spectrum of kidney disease (eGFR <90 mL/min/1.73 m2).
Methodological Strengths
- Large population-based cohort with new-user design and IPTW
- Use of recurrent event models to capture multiple ED/hospitalization episodes
Limitations
- Observational design with potential residual confounding despite weighting
- Lack of randomization and limited insight into cause-specific admissions
Future Directions: Prospective trials or pragmatic RCTs in CKD populations to confirm acute care reduction and explore mechanisms; subgroup analyses by eGFR, albuminuria, and comorbidities.