Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer beneficial renal effects in type 2 diabetes (T2D) patients with chronic kidney disease (CKD). Evidence extending these benefits to CKD-mineral and bone disorders (CKD-MBD) is lacking.
Aims: To investigate the incidence of CKD-MBD after SGLT2 inhibitor use in T2D patients with CKD.
Methods: We emulated CREDENCE, DAPA-CKD and EMPA-KIDNEY trials using Taiwan’s largest multi-institutional electronic medical records database. We included adults with T2D and CKD stages 1-3, initiating SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) during 2016-2021, with follow-up until December 31st, 2023. We controlled baseline characteristics using propensity scores with inverse probability of treatment weighting. The primary outcome was the incident composite CKD-MBD outcomes, namely: (1) hyperphosphatemia; (2) hypocalcemia; (3) serum iPTH levels >65 pg/mL and (4) serum 25-hydroxyvitamin D levels <20 ng/mL. Subgroup analysis assessed these outcomes’ association with individual inhibitors.
Results: The weighted cohort included 11,968 T2D patients with CKD stages 1-3, newly receiving SGLT2 inhibitors (n=10,661) or GLP-1 RAs (n=1,307). After the median 3.2 years follow-up, SGLT2 inhibitors were associated with lower cumulative incidence of composite CKD-MBD (HR: 0.82; 95%CI: 0.79-0.86), compared to GLP-1 RAs. Regarding individual outcomes, SGLT2 inhibitors were associated with significantly reduced risk for incident hyperphosphatemia (HR: 0.83; 95%CI: 0.76-0.91), hypocalcemia (HR: 0.82; 95% CI: 0.78-0.86), serum iPTH levels >65 pg/ml (HR: 0.66; 95% CI: 0.57-0.78) and serum 25-hydroxyvitamin D levels <20 ng/mL (HR: 0.65; 95% CI: 0.47-0.90). Subgroup analysis indicated the risk of composite CKD-MBD was significantly lower for empagliflozin (HR: 0.82; 95% CI: 0.77-0.87), dapagliflozin (HR: 0.82; 95% CI: 0.76-0.88), and canagliflozin (HR: 0.88; 95% CI: 0.78-1.00).
Conclusion:
SGLT2 inhibitors were associated with a reduced risk of composite and individual CKD-MBD outcomes. To reduce CKD-MBD incidence in T2D patients with CKD stages 1-3, SGLT2 inhibitors may be considered.

Introduction
Poorly controlled diabetes can lead to severe complications and increased mortality. Proper treatment is essential to prevent or delay the onset of these complications. In 2018, the American Diabetes Association updated its pharmacologic therapy guidelines based on comorbidities. However, few studies have investigated medication use patterns since the guideline updated. Our study aimed to track trends in antidiabetic medication usage and investigate whether patients with diabetes receive appropriate treatment.
Methods
Data from the 2018-2021 Medical Expenditure Panel Survey were used, which is a nationally representative annual survey in the U.S. with comprehensive information of medication use. Diabetes diagnoses were identified using ICD-10-CM codes, and antidiabetic medications were categorized using the Multum Lexicon database. Descriptive statistics were estimated using survey weights. Wald Chi-square tests were used to assess trend changes between 2018 and 2021. After pooling the 2018 and 2021 data, multivariable logistic regression models were used to calculate the adjusted odds ratio (aOR).
Results
The diagnosis of diabetes slightly increased from 2018 to 2021(7.4% vs. 7.6%, p=0.74). Among patients with diabetes, antidiabetic medication use significantly rose from 87.8% to 91.4% (p<0.05). Notable increases were observed in the use of metformin (59.1% vs. 65.0%, p<0.05), sodium-glucose cotransporter-2 (SGLT-2) inhibitors (4.5% vs. 10.0%, p<0.01), and glucagon-like peptide-1 receptor agonists (6.4% vs. 7.6%, p=0.38). Monotherapy use decreased (50.4% to 47.8%, p=0.29), while the use of triple therapy increased (9.7% to 12.5%, p=0.12). Patients with dyslipidemia were significantly more likely to use any antidiabetic medication (aOR: 2.24; 95% CI: 1.50-3.33) than those without dyslipidemia. Older patients (≥65 years) were more likely to use sulfonylureas (aOR: 1.66; 95% CI: 1.19-2.31) than younger patients.
Conclusion
The use of antidiabetic medications among patients with diabetes has significantly increased, particularly in the case of metformin and SGLT-2 inhibitors. This observed increase aligns with current guideline recommendations.

Introduction:
While the relationship between glycemic variability (GV) and acute kidney injury (AKI) has been a subject of interest, the specific association of GV with persistent AKI following noncardiac surgery is not well-established.

Aims:
This retrospective cohort study aimed to describe the patterns of different GV metrics within 48 hours after noncardiac major surgery, evaluate the association between GV and persistent AKI within the 7-day postoperative window, and compare the risk identification capabilities of various GV metrics for persistent AKI.

Methods:
A total of 10,937 patients across three medical centers in eastern China were enrolled. GV was characterized using coefficient of variation (CV), mean amplitude of glycemic excursions (MAGE), and blood glucose risk index (BGRI). Multivariable logistic regression examined the relationship between GV and AKI. Optimal cutoff values were determined through risk identification models, independent cohort from the INSPIRE database was used for external validation.

Results:
Higher GV was associated with an increased risk of persistent AKI (CV: OR = 1.26, 95% CI: 1.08-1.46; MAGE: OR = 1.31, 95% CI: 1.15-1.49; BGRI: OR = 1.18, 95% CI: 1.08-1.29). Compared to models that did not consider glycemic factors, MAGE and BGRI independently contributed to predicting persistent AKI (MAGE: AUC = 0.768, p = 0.011; BGRI: AUC = 0.764, p = 0.014), with cutoff points of 3.78 (MAGE) and 3.02 (BGRI), respectively. Classification of both the internal and external validation cohorts using these cutoffs demonstrated good performance, achieving the best AUC values of 0.768 for MAGE in the internal cohort and 0.777 for MAGE in the external cohort.

Discussion:
Postoperative GV is an independent risk factor for persistent AKI. Specific cutoff points are useful to stratify at-risk patients. These findings indicate that stabilizing GV may potentially mitigate adverse postoperative kidney outcomes, highlighting the importance of glycemic control in the perioperative period.

- Introduction: GLP-1RAs are frequently prescribed for managing type 2 diabetes. However, concerns have arisen regarding the risk of suicidal attempts associated with GLP-1RAs following the EMA announcement about a potential link. We conducted a study using a nationwide database to evaluate the risk.

- Aims: To evaluate the association between suicidal-related outcomes and the use of GLP-1RAs compared to the use of DPP4 inhibitors in the type 2 diabetes population in Taiwan.

- Methods: This is a retrospective cohort study. We applied propensity score matching, pairing controls for each case with the ratio of 1:1. Individuals enrolled in Taiwan's National Health Insurance Research Database (NHID) from 2016 to 2021 were included. The index date was defined as the date of the first prescription of GLP-1RAs or DPP4 inhibitors. Patients who initiated both medications simultaneously, used the opposite medication within three years prior to the index date, or had a record of suicidal attempts or depression within three years prior to the index date were excluded. The outcomes of interest were suicidal-related behaviors, including suicidal attempts and suicidal death. We applied an intention-to-treat design, and the follow-up period was defined from the index date to the occurrence of the outcome of interest, death, or the end of the study period (December 31, 2024), whichever came first. We evaluate the hazard ratio through Cox proportional hazard model.

- Results: We identified 694,054 cases of DPP4 inhibitors and 8,986 cases of GLP-1RAs. The HRs for suicidal attempts, suicidal deaths, and composite outcomes were 1.00 (0.61, 1.63), 0.75 (0.17, 3.35), and 0.97 (0.61, 1.55) respectively.

- Discussion/Conclusion: Our study indicates the risk of suicide-related outcomes is comparable between GLP-1RAs and DPP4 inhibitors, suggesting no significant difference in safety regarding suicidal behaviors.

- Keywords: GLP-1RAs, DPP4i , suicidal-related outcomes, National Health Insurance Research Database

Introduction: Both glucagon-like peptide-1 receptor agonist (GLP1rA) and pioglitazone on its own have been shown to possess cardio-hepatic benefits in patients with type 2 diabetes. However, their comparative effects in reducing adverse cardiovascular and liver outcomes remains undetermined.

Aims: We conducted this territory-wide target trial emulation study to compare the risks of developing major adverse cardiovascular events (MACE) and adverse liver outcomes between GLP1rA and pioglitazone users who had type 2 diabetes.

Methods: Using electronic health records of the Hospital Authority of Hong Kong, we emulated a target trial with an active-comparator new-user design on eligible patients with type 2 diabetes who were newly prescribed GLP1rA or pioglitazone between January 2008 and December 2022. New users of GLP1rA and pioglitazone were matched one-to-one using propensity score matching (PSM). Cox proportional hazards models were used to estimate the hazard ratios (HRs) of developing the primary outcomes of MACE and the adverse liver outcomes, using both intention-to-treat (ITT) and per-protocol (PP) analyses.

Results: A total of 8,786 patients were included after PSM. While there were no notable difference in the risk of developing adverse liver outcomes between new users of GLP1rA and pioglitazone (p=0.964 and p=0.895 in ITT and PP analyses, respectively), new users of GLP1rA had significantly lower risk of MACE compared to pioglitazone in both ITT (HR 0.73, 95% CI 0.61-0.88, p<0.001) and PP (HR 0.70, 95% CI 0.52-0.95, p=0.021) analyses. The results were consistent across most subgroup and sensitivity analyses.

Conclusion: With similar hepatic benefits, GLP1rA, as compared to pioglitazone, provides more reduction in MACE and may be the more promising agent for managing patients with type 2 diabetes who are at risk of both adverse cardiovascular and hepatic events, such as those with co-existing metabolic dysfunction-steatotic liver disease.

Cognitive impairment (CI) is a growing sequela of type 2 diabetes (T2D). Three newer glucose-lowering drugs (GLDs) are used as second-line therapy for T2D, i.e., glucagon-like peptide-1 receptor agonist (GLP-1RA), sodium-glucose transport protein 2 inhibitors (SGLT2i), or dipeptidyl peptidase 4 inhibitors (DPP4). Some data suggest that these GLDs may have cognitive benefits, however, comparisons across drug classes are scarce. We investigated the associations between newer GLD and cognitive health among adults with T2D.
Adults with diagnosed or self-reported T2D were identified from the Medical Expenditure Panel Surveys (2010-2020). We used Multum Lexicon codes to identify the person’s GLD use. We studied three groups: (1) adults filling Metformin plus DPP4, (2) adults filling Metformin plus SGLT2i, and (3) adults filling Metformin plus GLP-1RA. CI was measured during the survey interview using a questionnaire. The three groups were matched with a 1:1 multigroup propensity score algorithm based on age, sex, socioeconomic status, and comorbidities (e.g., obesity, cardiovascular disease). Logistic regression analyses were then conducted to compare the associations between newer GLD use and cognitive health, further adjusting for residual unbalanced covariates after matching.
We identified 418 (55.29%), 183 (29.22%), and 107 (15.49%) individuals who used Metformin plus DPP4, GLP-1RA, and SGLT2i, respectively. Prevalence of cognitive impairment was highest in the Metformin plus DPP4 group (15.19%, 95% Confidence Interval (CI): 14.81%-21.89%), followed by the Metformin plus SGLT2i (12.02%, 95% CI: 6.15%-12.14%), and lowest in Metformin plus GLP-1RA group (9.87%, 95% CI: 7.84%-14.38%). Adjusted for confounders, individuals using Metformin plus DPP4 were 1.83 times (95% CI: 1.08-3.09), and those using Metformin plus SGLT2i 1.79 times (1.14-2.83) more likely than those using Metformin plus GLP-IRA to report CI.
GLP-RA use was associated with lower odds of CI compared with either DPP4 or SGLT2i. Further studies are warranted to investigate the potential causal relationship.