Users Of Sodium-glucose Co-transporter-2 Inhibitors Research Articles

Use of SGLT2i Versus DPP-4i as an Add-On Therapy and the Risk of PAD-Related Surgical Events (Amputation, Stent Placement, or Vascular Surgery): A Cohort Study in Veterans With Diabetes

OBJECTIVE To compare the risk of composite peripheral artery disease (PAD) surgical outcome, including peripheral revascularization and amputation procedures, between new users of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP-4is). RESEARCH DESIGN AND METHODS This retrospective cohort study of U.S. veterans age ≥18 years with diabetes who received care from the Veterans Health Administration was performed from 1 October 2000 to 31 December 2021. Data were linked to Medicare, Medicaid, and the National Death Index. New use of SGLT2i or DPP-4i medications as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination was evaluated for an association with PAD surgical procedure for peripheral revascularization and amputation. A Cox proportional hazards model for time-to-PAD event analysis compared the risk of a PAD event between SGLT2is and DPP-4is in a propensity score–weighted cohort with a competing risk of death and allowance for events to occur up to 90 days or 360 days after stopping SGLT2is. RESULTS The weighted cohort included 76,072 SGLT2i vs. 75,833 DPP-4i use episodes. The median age was 69 years, HbA1c was 8.4% (interquartile range [IQR] 7.5–9.4%), and the median diabetes duration was 10.1 (IQR 6.6–14.6) years. There were 874 and 780 PAD events among SGLT2i and DPP-4i users, respectively, for an event rate of 11.2 (95% CI 10.5–11.9) and 10.0 (9.4–10.6) per 1,000 person-years (adjusted hazard ratio [aHR] 1.18 [95% CI 1.08–1.29]). When PAD events were allowed for 360 days after SGLT2i use ended, the aHR was 1.16 (95% CI 1.06–1.26). CONCLUSIONS SGLT2i as an add-on diabetes therapy was associated with an increased cause-specific hazard of PAD surgeries compared with DPP-4i.

SGLT2-inhibitors in diabetic patients with severe aortic stenosis and cardiac damage undergoing transcatheter aortic valve implantation (TAVI)

BackgroundA substantial number of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) experience adverse events after TAVI, with health care expenditure. We aimed to investigate cardiac remodeling and long-term outcomes in diabetic patients with severe AS, left ventricular ejection fraction (LVEF) < 50%, and extra-valvular cardiac damage (EVCD) undergoing TAVI treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus other glucose-lowering strategies (no-SGLT2i users).MethodsMulticenter international registry of consecutive diabetic patients with severe AS, LVEF < 50%, and EVCD undergoing TAVI. Based on glucose-lowering therapy at hospital discharge, patients were stratified in SGLT2i versus no-SGLT2i users. The primary endpoint was a composite of all-cause death and heart failure (HF)-hospitalization (major adverse cardiovascular events, MACE) at 2-year follow-up. Secondary outcomes included all-cause death, cardiovascular death, and HF hospitalization.ResultsThe study population included 311 patients, among which 24% were SGLT2i users. Within 1-year after TAVI, SGLT2i users experienced a higher rate of LV recovery (p = 0.032), especially those with baseline LVEF ≤ 30% (p = 0.026), despite the lower baseline LVEF. Patients not treated with SGLT2i were more likely to progress to a worse EVCD stage over time (p = 0.018). At 2-year follow-up, SGLT2i use was associated with a lower rate of MACE, all-cause death, and HF hospitalization (p < 0.01 for all). After adjusting for confounding factors, the use of SGLT2i emerged as an independent predictor of reduced MACE (HR = 0.45; 95% CI 0.17–0.75; p = 0.007), all-cause death (HR = 0.51; 95% CI 0.25–0.98; p = 0.042) and HF-hospitalization (HR = 0.40; 95% CI 0.27–0.62; p = 0.004).ConclusionsIn diabetic patients with severe AS, LVEF < 50%, and EVCD undergoing TAVI, the use of SGLT2i was associated with a more favorable cardiac remodeling and a reduced risk of MACE at 2-year follow-up.

The outcomes of SGLT-2 inhibitor utilization in diabetic kidney transplant recipients

Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated efficacy in reducing cardiovascular events and potentially improving kidney function in diabetic patients. This investigation analyzes the TriNetX database to assess the efficacy of SGLT-2i in diabetic kidney transplant recipients (KTR) concerning all-cause mortality, major adverse cardiac events (MACE), and major adverse kidney events (MAKE). The study includes type 2 diabetic patients over 18 who underwent kidney transplants between June 1, 2015, and June 1, 2023, with a focus on SGLT-2i use within the first three months post-transplant. After propensity score matching, the study compares 1970 SGLT-2i users with matched non-users. With a median follow-up of 3.4 years, SGLT-2i users showed significantly lower rates of all-cause mortality (adjusted hazard ratio [aHR]: 0.32), MACE (aHR: 0.48), and MAKE (aHR: 0.52). These findings indicate that SGLT-2i significantly reduces mortality and adverse events in diabetic KTR, underscoring its potential to improve post-transplant outcomes.

SGLT-2 inhibitors and mortality among patients with heart failure with reduced ejection fraction: linked database study

ObjectiveTo investigate the association between sodium-glucose cotransporter-2 (SGLT-2) inhibitor use and risk of all cause mortality among patients with heart failure with reduced ejection fraction.DesignLinked database study.SettingNational registers in Denmark,...

Erectile Dysfunction Risk Among Patients With Diabetes Mellitus Using Sodium-Glucose Cotransporter 2 Inhibitors.

The aim of this study was to explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared with a control group of non-SGLT2I use by propensity score matching approach. Cox proportional hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio with a 95% confidence interval. One lakhs fifty nine thousand seven hundred seventy three patients with DM using SGLT2I and 159,773 propensity score matching patients with DM who had never used SGLT2I were included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted hazard ratio = 1.55, 95% confidence interval = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.

Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes

Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Risk of Incident colorectal carcinoma in patients with type 2 diabetes on SGLT-2 inhibitor users: a population-based cohort study

Abstract Background Patients with type 2 diabetes (T2D) are at substantially higher risk for developing colorectal carcinoma (CC) than the general population. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use on the development of incident CC in patients with T2D, but the findings are inconsistent. Purpose This study aimed to examine the association between SGLT-2i use and incident CC risk in patients with T2D. Methods We conducted a nationwide retrospective cohort study using the National Health Insurance Research Database (2015–2021). The primary outcome was the risk of incident CC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Therefore, multiple Cox regression modeling was conducted to analyze the association between SGLT-2i use and incident CC risk in patients with T2D. Results 268,495 propensity score-matched pairs of patients with T2D using SGLT-2i and non-using SGLT-2i, 1557 and 1264 incident CCs were recorded, respectively. There was a decreased risk of incident CC for SGLT-2i users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.79, 95% CI 0.74–0.84) compared with non-SGLT-2i users. The sensitivity test for the propensity score 1:2-matched analyses showed similar result (adjusted HR 0.79, 95% CI 0.74–0.85). Conclusions This population-based cohort study found that SLGT2i user was associated with a lower risk of CC by 21% compared to non-SGLT-2i users in T2D patients. More studies are needed to credibly evaluate the effects of SGLT-2i therapy on CC prevention in patients with T2D.

Glucagon-like peptide-1 receptor agonists before upper gastrointestinal endoscopy and risk of pulmonary aspiration or discontinuation of procedure: cohort study

ObjectiveTo assess whether use of glucagon-like peptide-1 (GLP-1) receptor agonists before upper gastrointestinal endoscopy is associated with increased risk of pulmonary aspiration or discontinuation of the procedure compared with sodium-glucose...

Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study

BackgroundPatients with low-to-normal body mass index (BMI; < 25.0 kg/m2) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials.MethodsThis cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0–22.4, 22.5–24.9, 25.0–29.9, 30.0–34.9, and 35.0 ≤ kg/m2). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category.ResultsAmong participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m2, 1.9% [n = 5,350]; 20.0–22.4 kg/m2, 8.5% [n = 23,818]; and 22.5–24.9 kg/m2, 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m2, HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0–22.4 kg/m2, HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5–24.9 kg/m2, HR [95%CI] = 0.92 [0.84 to 1.01]).ConclusionsThe protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors.Graphical abstract

Superior benefits of sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors for diabetic kidney disease: A cohort study.

To compare cardiorenal outcomes of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) in a national diabetic kidney disease (DKD) population. A cohort study was conducted using Taiwan's National Health Insurance Research Database and Laboratory Databases. Propensity score-matched prevalent new users of SGLT-2is (n = 1524) and DPP-4is (n = 6005) during 2017-2018 were selected from adults with DKD and an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2. Composite renal outcomes included sustained eGFR decrease, renal failure and renal mortality. Composite cardiovascular (CV) outcomes included acute myocardial infarction, stroke, hospitalization for heart failure and CV death. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with DPP-4i users, SGLT-2i users had a reduced risk of composite renal endpoint (HR: 0.16; CI: 0.12-0.24), consistently for a prolonged time to 50% or higher eGFR decrease (HR 0.17; CI: 0.11-0.27), renal failure (HR: 0.14; CI: 0.08-0.23) and decreased renal death (HR: 0.10; CI: 0.01-0.70). SGLT-2i users had a better composite CV outcome than DPP-4i users (HR: 0.74; CI: 0.64-0.85), and lower risks of stroke (HR: 0.76; CI: 0.62-0.92) and hospitalization for heart failure (HR: 0.68; CI: 0.55-0.84). Findings were consistent in analyses stratified by concomitant antidiabetic agents or intervals between DKD diagnosis and study drug initiation. This study shows the superior cardiorenal benefits of SGLT-2is compared with DPP-4is in the DKD population, regardless of concomitant antidiabetic agents or time from DKD onset to study drug initiation. SGLT-2is should be prioritized in adult patients with DKD.

8722 Sodium-Glucose Cotransporter 2 Inhibitors And The Risk Of Kidney Cancer Among Patients With Type 2 Diabetes: A Population-Based Cohort Study

Abstract Disclosure: M. Lee: None. H. Kim: None. R. Kim: None. Y. Yang: None. S. Lee: None. E. Kang: None. There is an important need to develop clinical strategies to reduce the risk of incident kidney cancer, especially in patients with type 2 diabetes (T2D) and concomitant chronic kidney disease. Here, we investigated kidney cancer risk associated with sodium-glucose cotransporter 2 (SGLT2) inhibitor use in patients with T2D, using a nationwide cohort of the Korean National Health Insurance claims and health examination database. After 1:1 propensity score matching, 83,531 SGLT2 inhibitor users and 83,531 non-users on other oral glucose-lowering drugs were selected from 814,685 cancer-free participants, aged 20 to 79 years, who started oral glucose-lowering drugs for T2D from 2014 to 2018. During 559,738 person-years of follow-up, 143 (25.5 per 100,000 person-years) new kidney cancer events occurred. SGLT2 inhibitor use was associated with a 37% reduced risk of kidney cancer compared with other oral glucose-lowering drug use (18.1 vs. 29.9 per 100,000 person-years; hazard ratio [HR], 0.63; 95% CI, 0.43 to 0.92). The reduced kidney cancer risk by SGLT2 inhibitor use was consistent even after additional adjustment for all variables composing the propensity scores (HR, 0.64; 95% CI, 0.43 to 0.93) and regardless of age, sex, BMI, comorbidities, or diabetic complications including nephropathy (all p &amp;gt; 0.1 for interaction). SGLT2 inhibitor use may be a preferable option for patients with T2D at high risk of kidney cancer. Presentation: 6/3/2024

Glucose-Lowering Drugs and Primary Prevention of Chronic Kidney Disease in Type 2 Diabetes Patients: A Real-World Primary Care Study

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1–326.5) per 10,000 person-years. In the nested case–control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73–0.99 and AOR = 0.89; 95%CI: 0.74–1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56–0.94 and AOR = 0.64; 95%CI: 0.46–0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD.

GLP-1 Receptor Agonist Use and Risk of Suicide Death

Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk of suicidality and self-harm. To assess the association between use of GLP-1 receptor agonists and the risk of suicide death in routine clinical practice. This active-comparator new-user cohort study used nationwide register data from Sweden and Denmark from 2013 to 2021. Adults 18 to 84 years old who initiated treatment with GLP-1 receptor agonists or the comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data were analyzed from March to June 2024. Initiation of treatment with a GLP-1 receptor agonist or SGLT2 inhibitor. The primary outcome was suicide death recorded in the cause of death registers. Secondary outcomes were the composite of suicide death and nonfatal self-harm and the composite of incident depression and anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) with 95% CIs were calculated separately in the 2 countries and pooled in a meta-analysis. In total, 124 517 adults initiated a GLP-1 receptor agonist and 174 036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users, the mean (SD) age was 60 (13) years, and 45% were women. During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, -0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders. This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of GLP-1 receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders. Suicide death among GLP-1 receptor agonist users was rare, and the upper limit of the confidence interval was compatible with an absolute risk increase of no more than 0.16 events per 1000 person-years.

Sodium-glucose cotransporter 2 inhibitor therapy reduces the administration frequency of steroid injection in patients with diabetic macular edema: A cohort study using the Japanese health insurance claims database.

Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.

Generalizability and treatment with sodium-glucose co-trasporter-2 inhibitors (SGLT2i) among patients with type 2 diabetes: an assessment using an Italian primary care database.

This study aimed to assess the proportions of type 2 diabetes (T2D) subjects meeting cardiovascular outcome trials (CVOTs) criteria for sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and estimate SGLT2i utilization, along with associated demographic and clinical characteristics, in a primary care setting. T2D patients in Italy were selected between January 1, 2021, and December 31, 2022, from The Health Improvement Network (THIN®) database. Representativeness was determined by dividing patients meeting key inclusion criteria for four CVOTs (CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, VERTIS-CV) to the total T2D population. Demographic and clinical characteristics of eligible T2D subjects and SGLT2i users were compared, and logistic regression models assessed the likelihood of receiving SGLT2i. Out of 17,102 T2D patients, 8,828 met eligibility criteria for at least one CVOT. DECLARE-TIMI 58 exhibited the highest representativeness (51.1%), compared to CANVAS (21.1%), EMPA-REG OUTCOME (5.5%), and VERTIS-CV (4.9%) trials. Eligible CVOTs patients were older (74.6 vs. 68.3 years), with a longer disease duration (10.2 vs. 9.7 years), and higher established cardiovascular disease (CVD) prevalence (36.0 vs. 27.3%) compared to SGLT2i users. Less than 10% of eligible T2D patients received SGLT2i. Males (OR: 1.43; 95%CI: 1.24-1.66) were more likely to be prescribed SGLT2i than other antidiabetic drugs, while the elderly (80 + vs. 40-64 years, OR: 0.17; 95% CI: 0.14-0.22) were less likely. Eligible T2D patients with CVD reported an increased likelihood of receiving SGLT2is compared to other antidiabetics. This study highlights significant variability in the proportion of T2D subjects meeting SGLT2i CVOT inclusion criteria, with DECLARE-TIMI-58 being the most represented. Low SGLT2i prescription rates in the Italian primary care setting, along with substantial demographic and clinical differences between SGLT-2i users and T2D eligible patients, emphasize the need for targeted interventions to optimize the use of these medications in primary care settings.

Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Discontinuation in Patients with CKD.

Little is known about the association of discontinuation of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA) with outcomes in patients with chronic kidney disease (CKD). We identified adults with CKD stages 3-4 from 2005-2022 in the Veterans Affairs healthcare system. Individuals with an incident prescription for SGLT2 inhibitors or GLP-1 RAs were included, with the first fill date considered the index date. Factors associated with time to first treatment discontinuation, defined as an interruption in SGLT2 inhibitor or GLP-1 RA prescription for ≥90 days, were studied using Cox proportional hazards regression models. Associations of discontinuation 90-179 days and ≥180 days with death, myocardial infarction, coronary revascularization, hospitalization for heart failure, and ischemic stroke were assessed using Cox proportional hazards regression. Of 96,345 individuals who received an SGLT2 inhibitor and 60,020 who received a GLP-1 RA, at least one discontinuation occurred in 35,953 (37%) of SGLT2 inhibitor users and 28,407 (47%) of GLP-1 RA users. SGLT2 inhibitor users were 24% Black, 71% White, 71% age ≥70, and 84% with CKD stage 3a. GLP-1 RA users were 20% Black, 75% White, 63% age ≥70, and 81% with CKD stage 3a. Black race, Hispanic ethnicity, cerebrovascular disease, peripheral vascular disease, and ischemic heart disease were associated with discontinuation of both drug classes. Female sex and more advanced CKD stage were also associated with SGLT2 inhibitor discontinuation. SGLT2 inhibitor discontinuation ≥180 days was associated with death, (adjusted hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.58-1.77) and heart failure hospitalization, (adjusted HR 1.26, 95% CI 1.13-1.40). GLP-1 RA discontinuation ≥180 days was associated with death, (adjusted HR 1.97, 95% CI 1.87-2.07), myocardial infarction (adjusted HR 1.23, 95% CI 1.11-1.36), heart failure hospitalization (adjusted HR 1.48, 95% CI 1.33-1.64), and ischemic stroke (adjusted HR 1.24, 95% CI 1.14-1.35). SGLT2 inhibitor and GLP-1 RA discontinuation was common and associated with harmful outcomes in adults with CKD.

Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease

ObjectiveType 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate...

Effects on calcium phosphate homeostasis after sodium-glucose cotransporter 2 inhibitor in patients with advanced chronic kidney disease and type 2 diabetes mellitus

BackgroundThe effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on calcium phosphate homeostasis in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remain uncertain. MethodsA retrospective observational cohort study of patients with T2DM at CKD stage G3b-5ND who received SGLT2i as compared to control from 1 January 2015 through 31 December 2021 was recruited. Propensity score assignment at 1:3 ratio by logistic regression was done. All patients were followed for 12 months. Outcomes were changes in phosphate level. ResultsWe analyzed 1,450 SGLT2i users and 4,350 control subjects. At the 12th month, SGLT2i users had a slower increase in phosphate levels (absolute change: −0.01 ± 0.28 vs + 0.14 ± 0.34 mmol/L; percentage change: −0.74 % ± 25.56 vs + 10.88 ± 28.15 %, P for both < 0.001). The proportion of patients with high phosphate was lower with SGLT2i (8.2 % vs 24.6 % increase). In the generalized estimating equation, SGLT2i was linked to a longitudinal reduction in phosphate (B −0.039, P<0.001). ConclusionsSGLT2i can effectively slow down the progression of phosphate retention in advanced CKD with T2DM.

The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis.

The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability. Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis. With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses. Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

Kidney outcomes with SGLT2 inhibitor vs. DPP4 inhibitor use in older adults with diabetes.

While the kidney protective effects of sodium glucose co-transporter-2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes. Using a nationwide claims database, we studied 6354 older adults (≥ 60 years of age) who had diabetes and newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decline in the rate of estimated glomerular filtration rate (eGFR), which was obtained using a linear mixed-effects model with an unstructured covariance. Following propensity score matching, 6354 individuals including 1271 SGLT2 inhibitor users and 5083 DPP4 inhibitor users (median age: 68 [65-70] years); men, 60.4%; median eGFR:69.0 [59.1-79.0] ml/min/1.73 m2, median hemoglobin A1c [HbA1c]:6.9 [6.5-7.4]%) were analyzed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users (-0.97 [95% CI, -1.24 to -0.70] ml/min/1.73m2 vs. -1.83 [95% CI, -1.97 to -1.69] ml/min/1.73m2 per year; p for interaction<0.001). This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use, and baseline eGFR. Additionally, the risk of a≥20%, ≥ 30%, and≥40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than that in DPP4 inhibitor users. Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decline in eGFR was slower in individuals aged≥60 years with diabetes who were prescribed SGLT2 inhibitors compared to those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.