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).
BACKGROUND: Once-weekly insulin efsitora alfa (efsitora) is in development for the treatment of people with diabetes. The aim of the current study was to assess the efficacy and safety of once-weekly efsitora compared with daily insulin degludec (degludec) in adults with type 2 diabetes using basal insulin. METHODS: This randomised, 78-week, phase 3, parallel-design, open-label, treat-to-target, non-inferiority study (QWINT-3) was conducted at 127 sites across nine countries. Adults (aged ≥18 years) with type 2 diabetes currently treated with basal insulin, up to three non-insulin glucose-lowering medications without prandial insulin, and glycated haemoglobin A FINDINGS: Between March 8, 2022, and May 15, 2024, 1229 participants were enrolled and 986 (80%) were randomly allocated: 655 to the efsitora group and 331 to the degludec group, all of whom received at least one dose of study treatment. 871 (88%) of those randomly allocated completed 78 weeks of treatment. The population comprised 431 (44%) female and 555 (56%) male patients, median age was 62·0 years (IQR 54·0-68·0), baseline BMI was 29·65 kg/m INTERPRETATION: Efsitora is a well tolerated and efficacious once-weekly alternative to daily basal insulin, with a reduced injection frequency, for the treatment of adults with type 2 diabetes. FUNDING: Eli Lilly and Company.
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.
BACKGROUND: Insulin efsitora alfa (efsitora), a once-weekly basal insulin, has the potential to reduce the treatment burden of people with type 2 diabetes who require insulin. We aimed to assess the efficacy and safety of once-weekly efsitora compared with insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin. METHODS: This phase 3, randomised, 26-week, parallel-design, open-label, treat-to-target, non-inferiority study was done at 78 outpatient clinics and hospitals in Argentina, Germany, India, Italy, Mexico, Spain, and the USA (including Puerto Rico). Participants with type 2 diabetes (glycated haemoglobin [HbA FINDINGS: Between Aug 11, 2022, and Feb 27, 2024, 1037 study participants were screened and 730 were randomly assigned to efsitora (n=365) or glargine U100 (n=365). 369 (51%) of 730 participants were female and 361 (49%) were male, the mean participant age was 58·9 years (SD 10·5), and the mean participant BMI was 31·85 kg/m INTERPRETATION: Efsitora showed non-inferior HbA FUNDING: Eli Lilly and Company.
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.
OBJECTIVE: The aim of this study was to evaluate the effect of glucagon-like peptide 1 receptor agonist (GLP-1RA) versus dipeptidyl peptidase 4 inhibitor (DPP4i) initiation on emergency department (ED) visits and all-cause hospitalizations across the spectrum of kidney disease. RESEARCH DESIGN AND METHODS: This was a retrospective population-based observational cohort study in adults with an estimated glomerular filtration rate <90 mL/min/1.73 m2 using inverse probability of treatment weighting. The Prentice-Williams-Peterson (PWP) gap time model was used for the primary analysis. RESULTS: The cohort included 24,576 new users of a GLP-1RA and 23,600 DPP4i new users. GLP-1RA initiation was associated with a lower risk of all-cause ED encounters or hospitalizations (hazard ratio [HR] 0.90; 95% CI 0.87-0.94; P < 0.0001). This finding was consistent in confirmatory analyses using the Andersen-Gill model and the PWP calendar time model. CONCLUSIONS: GLP-1RA initiation was associated with a reduction in all-cause ED visits and hospitalizations compared with new use of a DPP4i.