Daily Endocrinology Research Analysis
Analyzed 38 papers and selected 3 impactful papers.
Summary
Analyzed 38 papers and selected 3 impactful articles.
Selected Articles
1. Real-world evidence for comparative safety of second-line antihyperglycemic agents in older adults with type 2 diabetes.
In 1.8 million adults ≥65 years, GLP-1 receptor agonists and SGLT2 inhibitors had substantially lower risks of hypoglycemia and hyperkalemia than sulfonylureas, while SGLT2 inhibitors carried a higher diabetic ketoacidosis risk versus GLP-1 RAs and sulfonylureas. The study used robust causal inference methods across nine US/EU databases.
Impact: Provides large-scale, clinically actionable safety comparisons for second-line diabetes therapies in the oldest and most vulnerable patients, a group often excluded from trials.
Clinical Implications: For older adults, consider GLP-1 RAs or SGLT2 inhibitors over sulfonylureas to mitigate hypoglycemia; monitor for ketoacidosis with SGLT2 inhibitors, especially in those with precipitating risks.
Key Findings
- GLP-1 receptor agonists and SGLT2 inhibitors had significantly lower hypoglycemia risk than sulfonylureas.
- GLP-1 receptor agonists reduced peripheral edema risk versus DPP-4 inhibitors.
- SGLT2 inhibitors increased diabetic ketoacidosis risk compared with GLP-1 receptor agonists and sulfonylureas.
- Analyses spanned nine US/EU databases with propensity score adjustment and empirical calibration.
Methodological Strengths
- Multinational, very large cohort (approximately 1.8 million participants) across nine databases
- Advanced confounding control with propensity score adjustment, empirical calibration, and prespecified diagnostics
Limitations
- Observational design susceptible to residual confounding and misclassification
- Heterogeneity across databases may affect consistency of effect estimates
Future Directions: Head-to-head randomized trials in very old and frail populations; risk–benefit stratification by frailty, renal function, and comorbidity burden; inclusion of patient-centered outcomes.
As prescribing of newer antihyperglycemic agents expands, there remains limited comparative safety data for older adults-a population particularly vulnerable to adverse drug events and underrepresented in clinical trials. We conduct a multinational cohort study using nine databases from the U.S. and Europe. Among adults aged ≥65, we compare eighteen safety outcomes across four classes of second-line antihyperglycemic agents. We use propensity score adjustment, empirical calibration, and prespecified diagnostics and estimated hazard ratios. In a cohort of 1.8 million, both GLP-1 receptor agonists and SGLT2 inhibitors are linked to significantly lower risks of hypoglycemia and hyperkalemia than sulfonylureas. GLP-1 receptor agonists show lower risks of peripheral edema than DPP-4 inhibitors. However, SGLT2 inhibitors are associated with a higher risk of diabetic ketoacidosis compared to GLP-1 receptor agonists and sulfonylureas. These results support informed, safety-conscious prescribing in the older adults underrepresented in clinical trials yet highly susceptible to adverse events.
2. Durvalumab plus tremelimumab for the treatment of patients with progressive, refractory advanced thyroid carcinoma: the phase II GETNE-DUTHY trial.
Dual PD-L1/CTLA-4 blockade with durvalumab plus tremelimumab achieved a 33% objective response in anaplastic thyroid carcinoma and met the 6-month overall survival endpoint, with modest activity in differentiated and medullary cohorts. Safety was consistent with class expectations without new signals.
Impact: Addresses a major therapeutic gap in anaplastic thyroid carcinoma with prospective evidence of benefit using dual checkpoint inhibition.
Clinical Implications: Dual checkpoint blockade may be a treatment option for anaplastic thyroid carcinoma in the refractory setting; more modest efficacy in differentiated and medullary disease suggests the need for biomarker-driven selection or combinations.
Key Findings
- In anaplastic thyroid carcinoma, 6-month overall survival was 65.6%, with an objective response rate of 33%.
- Differentiated and medullary cohorts had 6-month progression-free survival rates of 32.4% and 40.8%, with objective response rates of 8% and 10%, respectively.
- No new safety signals were observed with durvalumab plus tremelimumab.
Methodological Strengths
- Prospective phase II, multi-cohort design with predefined survival endpoints
- Includes heavily pretreated, refractory populations across distinct thyroid cancer subtypes
Limitations
- Single-arm, non-randomized design without a comparator arm
- Small sample size in the anaplastic cohort (n=12) limits precision
Future Directions: Randomized controlled trials, biomarker stratification (e.g., PD-L1, TMB), and rational combinations (e.g., with TKIs or radiation) to enhance efficacy.
Single-agent PD-1 blockade demonstrated promising efficacy in advanced thyroid cancer. The phase II, single-arm, multi-cohort GETNE-DUTHY trial (clinicaltrials.gov NCT03753919, EudraCT 2018-001066-42) aimed to determine whether dual anti-PD-L1/CTLA-4 inhibition using durvalumab and tremelimumab can improve the clinical outcomes in advanced thyroid cancer. Three parallel cohorts including patients with differentiated thyroid carcinoma (Cohort 1, n = 37), medullary thyroid carcinoma (Cohort 2, n = 30), and anaplastic thyroid carcinoma (Cohort 3, n = 12) were recruited. Cohort 1 and 2 included patients following progression to previous standard systemic therapy and in Cohort 3 were recruited regardless of previous therapy. The primary endpoint was 6-month progression-free survival rate for Cohort 1 and 2 and 6-month overall survival rate for Cohort 3. Secondary endpoints included objective response rate, progression-free survival, overall survival, and safety. The 6-month progression-free survival rates were 32.4% (95% confidence interval [CI]: 20.4-51.6) (Cohort 1) and 40.8% (95% CI: 26.3-63.6) (Cohort 2); 6-month overall survival rate was 65.6% (95% CI: 43.2-99.8) (Cohort 3). The objective response rates were 8%, 10%, and 33% for Cohort 1, 2, and 3, respectively. No additional safety signals observed. Durvalumab plus tremelimumab treatment in patients with anaplastic thyroid carcinoma met the primary endpoint of this study, showing encouraging survival outcomes.
3. Flash glucose monitoring addition to self-monitoring of blood glucose and perinatal outcomes in gestational diabetes: a randomized controlled trial.
In a single-center RCT of 205 low-risk gestational diabetes patients, adding flash glucose monitoring to standard SMBG did not improve the percentage of readings in target range. A lower rate of large-for-gestational-age neonates was observed as a secondary outcome, warranting cautious interpretation.
Impact: Provides randomized evidence clarifying that adjunctive flash monitoring does not enhance primary glycemic control in low-risk gestational diabetes, informing resource allocation and monitoring strategies.
Clinical Implications: SMBG remains standard for low-risk gestational diabetes; adjunctive flash monitoring should not be routine for glycemic targets but may warrant further study for potential perinatal benefits.
Key Findings
- Adjunctive flash glucose monitoring did not increase the percentage of SMBG readings within target range (primary outcome).
- Fewer large-for-gestational-age neonates occurred in the flash monitoring group as a secondary outcome.
- Intention-to-treat analysis in an open-label, single-center RCT with 205 participants.
Methodological Strengths
- Randomized controlled design with intention-to-treat analysis
- Prespecified maternal and neonatal secondary outcomes
Limitations
- Open-label, single-center design may limit generalizability and introduce performance bias
- Sample size and event counts may be underpowered for perinatal outcomes
Future Directions: Multicenter blinded RCTs powered for perinatal outcomes; subgroup analyses by treatment modality and baseline risk; cost-effectiveness of adjunctive monitoring.
OBJECTIVE: Self-monitoring of blood glucose represents the standard for glycemic monitoring in gestational diabetes mellitus, while the role of continuous glucose monitoring remains uncertain. METHODS: We conducted an open-label, single-center, randomized controlled trial comparing adjunctive flash glucose monitoring plus self-monitoring of blood glucose with self-monitoring of blood glucose alone. The prespecified primary outcome was the percentage of self-monitored glucose measurements within the established target range. Secondary outcomes included maternal and neonatal outcomes. Analyses followed the intention-to-treat principle. RESULTS: A total of 205 women (median age 32 years; median pre-pregnancy body mass index 23.5 kg/m CONCLUSIONS: Adjunctive flash glucose monitoring did not improve glycemic outcome in this low-risk gestational diabetes population. However, it was associated with fewer large-for-gestational-age neonates, a secondary outcome that should be interpreted cautiously given the sample size and number of events.