Use Of Pioglitazone Research Articles

Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes-A real-world study.

Both pioglitazone and glucagon-like peptide 1 receptor agonists (GLP1RA) alone improve metabolic dysfunction-associated steatohepatitis (MASH) in randomized clinical trials, whereas preclinical studies suggested MASH benefits with sodium glucose co-transporter 2 inhibitors (SGLT2i). In the real world, patients with type 2 diabetes often require multiple agents for glycaemic control. Here, we investigated the benefits of combining these agents on risks of MASH. Longitudinal changes in FibroScan-aspartate aminotransferase (FAST) score were measured in 888 patients with type 2 diabetes. Use of pioglitazone, GLP1RA and/or SGLT2i was defined as continuous prescriptions of ≥180 days prior to their last reassessment FibroScan. Multivariable logistic regression analysis was conducted to evaluate the associations between use of these agents and FAST score changes. Over a median follow-up of 3.9 years, the increasing number of these agents used was significantly associated with more reductions in FAST score (p for trend <0.01). Dual combination was independently associated with a higher likelihood of achieving low FAST score at reassessment than single use of any of these agents (odds ratio [OR] 2.84, p = 0.01). Among the different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together, as compared to not using any of these three agents, was associated with a higher likelihood of both low FAST score at reassessment (OR 6.51, p = 0.008) and FAST score regression (OR 12.52, p = 0.009), after adjusting for changes in glycaemic control and body weight during the study. Combining SGLT2i and pioglitazone is a potentially useful strategy to ameliorate 'at-risk' MASH in patients with type 2 diabetes.

Screening For Occult Heart Failure in Type 2 Diabetes Mellitus Using NT-proBNP: Real-World Evidence From a Tertiary Care Center in India.

Objective Heart failure (HF) is an important underrecognized complication of type 2 diabetes mellitus (T2DM). Recent literature and recommendations support screening for HF among T2DM people attending the outpatient department (OPD) in non-emergency settings using a biomarker. The present study is a retrospective cross-sectional study that assesses the prevalence of screen positivity (S+) for undiagnosed HF among T2DM people (with normal electrocardiogram (ECG) and no history of heart disease) attending the OPD at a tertiary care center in India using N-terminal pro-B-type natriuretic peptide (NT-proBNP). It also highlights the risk factors for S+ for HF. Methods This is a retrospective cross-sectional study of the practice of NT-proBNP screening in T2DM to diagnose stage B HF. A total of 1,049 consecutive people with T2DM (age range: 18-75 years) attending the OPD of a tertiary care institute in India were screened for HF using NT-proBNP (cut off S+ >125 pg/mL). Demographic variables, vitals, smoking status, family history, status of hypertension, medications for diabetes, and glycemic control were recorded and correlated with the risk of S+ for HF. Results Of the 1,049 people with T2DM, 336 (32.03%) had S+ for HF. Those with S+ had higher age (62.5+9.3 vs 54.2 +10.6 years), longer duration of T2DM (14.4 +7.8 vs 9.6 +6.1 years), positive history for smoking (94 [28%] vs 55 [7.7%]) and tobacco chewing (66 [19.6%] vs 24 [3.4%]), higher blood pressures (both systolic [152.1+19.9 vs 134.6 +15 mmHg] and diastolic [87.7+9.6 vs 83.9+7.8 mmHg]), higher glycated hemoglobin (HbA1c) (8.4+1.4 vs 7.6+1 years), higher BMI (28.3+2.8 vs 27.2+2.1 kg/m2), presence of chronic kidney disease (CKD) (210 [62.5 %] vs 118 [16.5%]), and a positive family history of cardiac ailments (185 [55.1%] vs 122 [17.1%]) (p<0.05 for all). The above factors also correlated with increased chances of S+ for HF on regression analysis. Conclusion S+ for HF is common in people with T2DM attending OPDs. The S+ was associated with increasing age, longer duration of T2DM, smoking and tobacco chewing, uncontrolled hypertension and T2DM, obesity, the presence of CKD, use of pioglitazone and insulin, and positive family history. It is the need of the hour to widely extend routine screening for HF in T2DM patients using NT-proBNP in the OPD setting so that benefits of guideline-based therapy can be extended.

Effects of SGLT2i and Pioglitazone on FIB-4 Index in Patients with Metabolic Dysfunction Associated Steatotic Liver Disease—A Real World Retrospective Study from India

Aims: Several studies support type 2 diabetes mellitus (T2DM) as one of the risk factors of metabolic dysfunction associated steatotic liver disease (MASLD). Recently, the use of pioglitazone and sodium-glucose co-transporter 2 inhibitors (SGLT2i) has been on the rise considering its beneficial effects in reducing liver dysfunction. We aim to determine the clinical effectiveness of these drugs in improving MASLD and T2DM. Materials and methods: We conducted a retrospective study of 279 T2DM patients with MASLD who were prescribed pioglitazone and/or SGLT2i from two clinics in India. The primary endpoint was change in fibrosis (FIB-4) index and the aspartate aminotransferase to platelet ratio index (APRI) score at one year follow-up. Appropriate statistical tests were applied to assess the significance of the outcomes. Results: Of the total (276) patients, 46% of patients were at low risk of advanced fibrosis, 11% were at high risk for advanced fibrosis, and the majority (50%) were on SGLT2i treatment. At follow-up, there is a statistically significant reduction in the mean (SD) FIB-4 index (1.92 [1.22] vs. 1.68 [0.99]) and APRI score (0.42 [0.34] vs. 0.33 [0.21]); p &lt; .001. Among treatment groups, there is a significant difference in the mean FIB-4 index both at baseline (F: 4.23; p &lt; .05) and follow-up (F: 3.45; p &lt; .05). These scores were highly significant in the combination treatment with SGLT2i and pioglitazone ( p &lt; .05). Conclusions: Our results indicate a combination therapy with SGLT2i and pioglitazone might be beneficial in managing MASLD, especially in reducing the FIB-4 index and APRI score in Indian T2DM patients with MASLD.

Metabolic associated fatty liver disease (MAFLD): assessing the knowledge and practice of primary care doctors in Seremban District, Negeri Sembilan.

Metabolic-associated fatty liver disease (MAFLD) is the liver manifestation of metabolic syndrome, which is commonly seen in primary care settings. This study aimed to determine the knowledge and practice of primary care physicians regarding MAFLD in Seremban District, Negeri Sembilan. This cross-sectional study was conducted among medical officers in 14 health clinics in Seremban District, using a validated, self-administered online questionnaire. A total of 240 medical officers from 14 health clinics in Seremban District, participated in this study. Most participants (85.4%) passed the knowledge test. Their practice was acceptable, but only a minority were familiar with non-invasive testing of liver fibrosis (e.g. APRI or FIB-4), medication and specific diet for the treatment of MAFLD. Most primary care physicians in Seremban District are knowledgeable in identifying risk factors and managing patients with MAFLD. However, there are still areas to improve in terms of management, particularly regarding the use of silymarin, vitamin E and pioglitazone.

Metformin in Chemoprevention of Lung Cancer: A Retrospective Population-Based Cohort Study in Lithuania.

Background and Objectives: This study aimed to evaluate the potential chemopreventive effect of antidiabetic medications, specifically metformin and pioglitazone, on lung cancer in patients with type 2 diabetes mellitus (T2DM). Additionally, the potential dose-response relationship for metformin use was analyzed. Methods: We conducted a retrospective cohort study utilizing comprehensive national health insurance and cancer registry databases to gather a large cohort of T2DM patients. Cox proportional hazards regression models were used to assess the risk of lung cancer across different antidiabetic medication groups, adjusting for potential confounders such as age and gender. A dose-response analysis was conducted for metformin users. Results: Our results indicated that metformin users had a significantly lower lung cancer risk than the reference group (HR = 0.69, 95% CI [0.55-0.86], p = 0.001). The risk reduction increased with higher cumulative metformin doses: a metformin cumulative dose between 1,370,000 and 2,976,000 had an HR of 0.61 (95% CI [0.49-0.75], p < 0.001) vs. cumulative metformin dose >2,976,000 which had an HR of 0.35 (95% CI [0.21-0.59], p < 0.001). No significant association between pioglitazone use and the risk of lung cancer was found (HR = 1.00, 95% CI [0.25-4.02]). Conclusions: This study shows that metformin may have a dose-dependent chemopreventive effect against lung cancer in T2DM, while the impact of pioglitazone remains unclear and requires further investigation.

Pioglitazone does not enhance exogenous glucose oxidation or metabolic clearance rate during aerobic exercise in men under acute high-altitude exposure.

Insulin insensitivity decreases exogenous glucose oxidation and metabolic clearance rate (MCR) during aerobic exercise in unacclimatized lowlanders at high altitude (HA). Whether use of an oral insulin sensitizer before acute HA exposure enhances exogenous glucose oxidation is unclear. This study investigated the impact of pioglitazone (PIO) on exogenous glucose oxidation and glucose turnover compared with placebo (PLA) during aerobic exercise at HA. With the use of a randomized crossover design, native lowlanders (n = 7 males, means ± SD, age: 23 ± 6 yr, body mass: 84 ± 11 kg) consumed 145 g (1.8 g/min) of glucose while performing 80 min of steady-state (1.43 ± 0.16 V̇o2 L/min) treadmill exercise at HA (460 mmHg; [Formula: see text] 96.6 mmHg) following short-term (5 days) use of PIO (15 mg oral dose per day) or PLA (microcrystalline cellulose pill). Substrate oxidation and glucose turnover were determined using indirect calorimetry and stable isotopes ([13C]glucose and 6,6-[2H2]glucose). Exogenous glucose oxidation was not different between PIO (0.31 ± 0.03 g/min) and PLA (0.32 ± 0.09 g/min). Total carbohydrate oxidation (PIO: 1.65 ± 0.22 g/min, PLA: 1.68 ± 0.32 g/min) or fat oxidation (PIO: 0.10 ± 0.0.08 g/min, PLA: 0.09 ± 0.07 g/min) was not different between treatments. There was no treatment effect on glucose rate of appearance (PIO: 2.46 ± 0.27, PLA: 2.43 ± 0.27 mg/kg/min), disappearance (PIO: 2.19 ± 0.17, PLA: 2.20 ± 0.22 mg/kg/min), or MCR (PIO: 1.63 ± 0.37, PLA: 1.73 ± 0.40 mL/kg/min). Results from this study indicate that PIO is not an effective intervention to enhance exogenous glucose oxidation or MCR during acute HA exposure. Lack of effect with PIO suggests that the etiology of glucose metabolism dysregulation during acute HA exposure may not result from insulin resistance in peripheral tissues.NEW & NOTEWORTHY Short-term (5 days) use of the oral insulin sensitizer pioglitazone does not alter circulating glucose or insulin responses to enhance exogenous glucose oxidation during steady-state aerobic exercise in young healthy men under simulated acute (8 h) high-altitude (460 mmHg) conditions. These results indicate that dysregulations in glucose metabolism in native lowlanders sojourning at high altitude may not be due to insulin resistance at peripheral tissue.

Risk of diabetic retinopathy and diabetic macular oedema with sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database

Aims/hypothesisA protective role of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin.MethodsThis is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan–Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA1c, BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed.ResultsSGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208).Conclusions/interpretationOur study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated retinal imaging are required to determine the causal relationship with these therapies.Graphical

Risk of gout flare after medication: prescription symmetry sequence analysis.

The research aimed to study the following questions: (1) five well-known gout-related medications were selected to test the validity of the prescription symmetry sequence analysis in Taiwan; (2) four exploratory medications were selected to test their relation to gout flares. We utilized the 2003-2017 dataset of the Taiwan National Health Insurance Program containing all claims data with 2 million beneficiaries as a data source. In order to explore the temporal association, we designed a scenario of medication-induced gout flares. Nine medications were selected as the index agent, including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, pyrazinamide, metformin, pioglitazone, fenofibrate, and losartan. The gout flare was defined as subjects with use of the marker agent for treatment of gout flares. The observation-window period between initiation of the index agent and initiation of the marker agent was 1year. Subjects who used an index agent and a marker agent on the same day were excluded. The prescription symmetry sequence analysis was carried out to compare the observed number of persons who took an index agent prior to starting a marker agent with the observed number of persons who took a marker agent before starting an index agent. The adjusted sequence ratio (adjusted SR) with 95% confidence interval was applied to estimate the relation between an index agent and the marker agent. Among five medications including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, and pyrazinamide, the adjusted sequence ratio ranged from 1.15 to 3.35 and all reached statistical significance. Fenofibrate use and losartan use were associated with a lower probability of gout flares, with reaching statistical significance (adjusted SR = 0.60 for fenofibrate and adjusted SR = 0.92 for losartan). Metformin use was associated with a greater probability of gout flares, with reaching statistical significance (adjusted SR = 1.14). Pioglitazone use did not reach statistical significance. Based on the confirmatory analysis including five well-known gout-related medications, this study supports that the prescription symmetry sequence analysis can be used to detect an adverse drug event associated with one potential offending agent. The exposure to fenofibrate or losartan might be a protective factor against gout flares. Metformin use could be associated with a greater probability of gout flares, but this finding should be validated by other studies. • What is already known about this subject? 1. The prescription symmetry sequence analysis is a useful method for detecting an adverse drug reaction associated with one potential offending drug. 2. Numerous medications are found to induce gout flares. • What does this study add? 1. The prescription symmetry sequence analysis supports the evidence that aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol and pyrazinamide are associated with a greater probability of gout flares. 2. The exposure to fenofibrate or losartan might be a protective factor against gout flares. 3. Metformin use could be associated with a greater probability of gout flares. • How might this impact on clinical practice or future developments? 1. Clinicians should always consider the possibility of medication-induced gout flares. If gout flares develop, discontinuation of risky medications is the first step. Then prescribing cascades can be eliminated.

To Conduct a Prospective Study on Pioglitazone Induced Kidney Injury in Tertiary Care Hospital

Conducting a prospective study on kidney impairment caused by pioglitazone at tertiary care hospitals is the study's goal. The goal is to assess Pioglitazone, mortality, quality of life, and the degree of the medication's harmful side effects in diabetic patients. According to the "Pioglitazone-induced kidney injury" prospective study. Out of 350 trial participants, prolonged pioglitazone use in diabetic patients has been shown to raise serum creatinine levels by up to 11%. Additionally, individuals who have been using pioglitazone for six to ten years are more likely to experience renal injury, with males in the 50–60 year age range being the most common victims.&#x0D; Keywords: Pioglitazone, diabetic, prospective, tertiary care, hospital.

Pioglitazone in spontaneous subarachnoid hemorrhage: study protocol of a multicenter, double-blind, randomized trial (PSSH).

Introduction: Spontaneous subarachnoid hemorrhage (SAH), is a disorder that may be fatal and is primarily caused by a ruptured brain aneurysm. Despite significant leaps forward in the methods to produce aneurysms, the long-term outcomes did not much improve. Pioglitazone is a medication that has been authorized by the FDA as an agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ). Pioglitazone or PPARγ has neuroprotective benefits in animal experiments both during and after traumatic brain injury (TBI) and SAH. Nevertheless, the treatment impact of Pioglitazone on humans is still unknown at this time. As a result, we will conduct a randomized, double-blind, placebo-controlled trial to explore the impact of pioglitazone on SAH. Methods/Design: This trial will recruit 400 patients with SAH from four Chinese hospitals. These patients will be equally and randomly assigned to Pioglitazone and placebo control groups for up to 30 days. Scores on the modified Rankin scale (mRS) are the primary outcomes. The secondary outcomes are a 30-day all-cause mortality rate, 6months of Montreal cognitive assessment (Mo-CA), delayed cerebral ischemia, the requirement for intensive care, the incidence of sepsis, etc. All serious adverse events (SAEs) were recorded during the hospital. Every primary and safety analysis was conducted based on the intention-to-treat technique. The participants were given either a matching placebo or 15mg of pioglitazone, with dose titrated to a target of 45mg daily. Data on the therapeutic use of pioglitazone after SAH will be provided as a consequence of the findings of this experiment. In addition, this pilot trial is the first to prospectively investigate the effectiveness and safety of pioglitazone in patients with SAH. Ethics and dissemination: Ethics approval was obtained from the Medical Ethics Committee of 904th Hospital of Joint Logistic Support Force of PLA (Wuxi Taihu Hospital, approval No. 20220701). The findings of the trial will be presented at conferences, discussed in relevant patient groups, and published in peer-reviewed journals. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2200062954.

Effects of pioglitazone and metformin on abdominal adhesion formation in an experimental model.

This study evaluated the use of metformin or pioglitazone in preventing or reducing the development of post-operative intra-abdominal adhesion (PIAA) by employing histopathological, immunohistochemical, and biochemical analyses in an experimental adhesion model. Fifty Wistar-Albino rats were divided into five groups: Group I (Control), Group II (Sham Treatment), Group III (Hy-aluronic Acid), Group IV (Metformin), and Group V (Pioglitazone). Adhesions were induced in the experimental groups, except for the sham group, using the scraping method. After 10 days, rats were euthanized for evaluation. Macroscopic adhesion degrees were assessed using Nair's scoring system. Immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods were utilized to assess serum, peritoneal lavage, and intestinal tissue samples. Fructosamine, interleukin-6 (IL-6), transforming growth factor-beta (TGF-β), and fibronectin levels were measured in serum and peritoneal lavage samples. The groups exhibited similar Nair scores and Type I or Type III Collagen staining scores (all, p>0.05). Pioglitazone significantly reduced serum IL-6 and TGF-β levels compared to controls (p=0.002 and p=0.008, respectively). Both metformin and pioglitazone groups showed elevated IL-6 in peritoneal lavage relative to controls, while fibronectin levels in the lavage were lower in pioglitazone-treated rats compared to the sham group (all, p<0.005). Pioglitazone, but not metformin, demonstrated a positive biochemical impact on preventing PIAA formation in an experimental rat model, although histological impacts were not observed. Further experimental studies employing different dose/duration regimens of pioglitazone are needed to enhance our understanding of its effect on PIAA formation.

Comprehensive understanding of stroke risk, prognosis, and preventive strategies for type 2 diabetes

Stroke is a serious and disabling disease with a high mortality rate that is becoming increasingly common worldwide, posing a serious threat to the health and quality of life of patients. Type 2 diabetes plays a special role in increasing the risk of stroke, which not only increases the risk of developing a stroke, but also negatively affects the outcome and the possibility of recurrent strokes.In order to prevent stroke, systematic action is necessary, including the correction of risk factors and the use of effective medications. One such drug is pioglitazone. Many studies support its effectiveness in reducing the risk of cardiovascular events, including stroke, for both secondary and primary prevention.Pioglitazone may be particularly beneficial for patients at high risk of cardiovascular disease and those with a history of ischemic brain damage. Despite the known side effects, its benefits in preventing stroke outweigh the possible disadvantages.This review provides important aspects of the role of type 2 diabetes mellitus in increasing the risk of stroke and discusses the prospects for the use of pioglitazone as a drug therapy affecting stroke risk and prognosis.

Multi-Target Neuroprotection of Thiazolidinediones on Alzheimer's Disease via Neuroinflammation and Ferroptosis.

Alzheimer's disease (AD) is the main cause of dementia in older age. The prevalence of AD is growing worldwide, causing a tremendous burden to societies and families. Due to the complexity of its pathogenesis, the current treatment of AD is not satisfactory, and drugs acting on a single target may not prevent AD progression. This review summarizes the multi-target pharmacological effects of thiazolidinediones (TZDs) on AD. TZDs act as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and long-chain acyl-CoA synthetase family member 4 (ACSL4) inhibitors. TZDs ameliorated neuroinflammation and ferroptosis in preclinical models of AD. Here, we discussed recent findings from clinical trials of pioglitazone in the treatment of AD, ischemic stroke, and atherosclerosis. We also dissected the major limitations in the clinical application of pioglitazone and explained the potential benefit of pioglitazone in AD. We recommend the use of pioglitazone to prevent cognitive decline and lower AD risk in a specific group of patients.

Toward a Precision Treatment Approach for Metabolic Depression: Integrating Epidemiology, Neuroscience, and Psychiatry

BackgroundIndividuals with comorbid major depressive disorder and type 2 diabetes represent an important subgroup of patients for whom conventional treatment may be insufficient. A precision treatment approach that addresses insulin resistance with an outcome of a positive response to antidepressants may prove beneficial. MethodsThis study utilized an emulated target trial on a large dataset from the Optum Clinformatics Data Mart Database. We evaluated the effect of adjuvant pioglitazone, an insulin-sensitizing drug, on antidepressant response among 4696 people with type 2 diabetes, comparing it with DPP4 (dipeptidyl peptidase-4) inhibitors (non–insulin-sensitizing). An additional analysis involving 6518 participants was conducted to assess the efficacy of pioglitazone versus sulfonylureas. ResultsThe instrumental variable analysis indicated that the initiation of an antidepressant with pioglitazone was superior to DPP4 inhibitors in terms of antidepressant response, with fewer treatment shifts and/or additions of new antidepressant or antipsychotic over a 1-year period. This result was consistent when pioglitazone was compared with sulfonylureas in a supplemental analysis. ConclusionsOur findings suggest that pioglitazone may be more effective than DPP4 inhibitors or sulfonylureas in enhancing antidepressant response among people with comorbid major depressive disorder and type 2 diabetes. This provides a strong case for the use of pioglitazone in patients with these conditions, emphasizing the potential of precision medicine strategies. The results should be interpreted with caution due to inherent limitations associated with observational data.

The effect of long-term use of pioglitazone on bone mineral density in patients with diabetes mellitus

Aims: This study aimed to explore the incidence of osteoporosis in patients with diabetes mellitus (DM) who have been on a long-term pioglitazone regimen, and to ascertain the link between pioglitazone usage and the onset of osteoporosis.&#x0D; Methods: We enrolled patients prospectively and conducted a comparative analysis between two groups of DM patients: those who had been using pioglitazone for a period exceeding two years, and those with no history of pioglitazone use. Bone Mineral Density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA).&#x0D; Results: There were no significant differences in age, gender, disease duration, fasting plasma glucose levels, and HbA1c levels between pioglitazone users and non-users. However, a significant variation was found in the BMD measurements. Patients on pioglitazone had an L1-L4 vertebra BMD T-score of -1.3, compared to -0.9 in non-users (p

1359-P: Gaps in the Use of Evidence-Based Diabetes Medications for NASH

Patients with type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH) are at exceedingly high risk of NASH progression to cirrhosis and end-stage liver disease. T2D medications shown to improve histologic features of NASH, such as GLP-1 receptor agonists and pioglitazone, should be considered for use in all patients with T2D and NASH, unless contraindications exist. However, utilization of T2D medications that benefit NASH are poorly understood. Our objective was to address this gap by examining their use in patients with T2D and NASH engaged with Primary and/or Endocrinology care in the Duke University Healthcare System between 1/1/2019 and 1/1/2021. T2D and NASH were defined by ICD-10 codes, E11.xx and K75.81, respectively and 848 patients were included in the analyses. Mean age of our cohort was 60 (SD 12) years, 62% were female (n=525), 13% (n=110) were Black race and 4.7% (n=40) were Hispanic ethnicity. The mean HbA1c was 7.5% (SD 1.5), and the majority followed with Endocrinology (58.5%, n=496) and used insulin (62.4%, n=529). Only 26.3% (n=223) had an appointment with Duke Hepatology during the study period (either new consultation or follow-up visit). The use of evidence-based T2D medications for NASH was low (34.8%, n=295), with only 31.3% (n=265) and 6.5% (n=55) of patients having been prescribed a GLP-1 receptor agonist or pioglitazone during the study period, respectively. Prescriptions of these medications did not significantly vary by race (Black vs. White unadjusted OR 1.08, 95% CI 0.71, 1.64) or Hispanic ethnicity (unadjusted OR, 1.46, 95% CI 0.77, 2.79). In summary, we observed a large gap between recommended and current use of evidence-based medications for NASH in patients with T2D. Use of pioglitazone was particularly low, despite its low cost and longstanding evidence for use in NASH. Future studies should explore reasons for underuse of these evidence-based T2D medications in NASH, and whether this is changing over time with growing evidence supporting their use in NASH. Disclosure A. Alexopoulos: None. A. Parish: None. M. Olsen: None. B. Batch: Advisory Panel; LLENA (AI). C.A. Moylan: Advisory Panel; Boehringer Ingelheim Inc. Research Support; GlaxoSmithKline plc. M.J. Crowley: None. Funding National Institutes of Health (KL2TR002554)

1115-P: Advanced Medical Therapy (AMT) for Youth-Onset Type 2 Diabetes (T2D)—Early Results from the Run-in Phase of ST2OMP

The Surgical or Medical Treatment for Pediatric Type 2 Diabetes (ST2OMP) study is a prospective open label clinical trial comparing metabolic bariatric surgery (MBS) to AMT for teens with youth-onset T2D. Prior to study group assignment, youth participate in a 6-month run-in period and receive AMT defined as multidrug, treat-to-target medical therapy to achieve an HbA1c &amp;lt;6.5%. Here, we examine the effects of AMT on metabolic parameters during run-in on the initial 51 participants. Participants in ST2OMP (57% female, 30% Black, 38% Hispanic, 25% White) were a mean age of 16.8 years, median diabetes duration 1.1 years, and median HbA1c 6.5% at screening (49% with HbA1c &amp;lt;6.5%). During run-in, metformin or pioglitazone use alone decreased (35.3% to 31.4%), as did insulin use (37.3% to 31.4%), while use of SGLT-2 inhibitors or GLP-1 agonists alone, or dual or triple therapy without insulin increased (21.6% to 31.4%). There was a small decrease in BMI, triglycerides and ALT, but a small increase in systolic and diastolic BP and total cholesterol, and decrease in HDL. At completion of run-in, 49% had an HbA1c of &amp;lt;6.5%. During a 6-month run-in period, AMT, using alternatives to insulin resulted in reduced need for insulin with favorable effects in some metabolic parameters, without worsening glycemic control. Full cohort recruitment and two-year follow-up in ST2OMP will determine the benefits of AMT vs. MBS. Disclosure A.S.Shah: None. A.Bailey: None. T.Inge: None. M.Helmrath: None. K.J.Nadeau: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc., Lilly. T.M.Jenkins: None. L.R.Schaaf: None. S.Xanthakos: None. A.T.Trout: Consultant; Lantheus, General Electric Co., Research Support; Canon America Medical Systems, Siemens, Perspectum Ltd. A.Baumgartner: None. A.Riegler: None. N.Krishnan: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119450)

892-P: Influence of Preceding Medications on the Renal Outcomes of Japanese Diabetics Treated with SGLT2 Inhibitors and GLP-1 Receptor Agonists

Background/Objective: Evidence of cardiovascular and renal outcomes has already been shown for SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1Ras); therefore, combination therapy with these drugs is of clinical interest. This study aimed to evaluate the effect of the preceding drug for patients with the combination treatment of SGLT2i and GLP1Ra on renal outcomes. Methods: We retrospectively extracted data of patients with type 2 diabetes mellitus who had received both SGLT2i and GLP1Ra treatment for at least 1-year at 18 medical facilities in Japan. Finally, 341 patients in the GLP1Ra-preceding group and 319 in the SGLT2i-preceding group were analyzed. The renal composite outcome was progression of the albuminuria stage, ≥30% decrease in eGFR, or both. The multiple imputation method for missing values and an inverse probability weighting method using the propensity score were used for the comparison of outcome. Results: The median observation period and the incidence of the renal composite outcome in the SGLT2i-preceding group and the GLP1Ra-preceding group was 55.1months, 26.9% and 58.7months, 25.6%, respectively, with an odds ratio (OR) [95% confidence interval] of 1.50 [0.89, 2.53] (p=0.13). The ORs for the ≥30% decrease in eGFR and the progression of albuminuria stage were 0.96 [0.47, 2.00] (p=0.93) and 1.76 [0.97, 3.69] (p=0.06), respectively. Compared to the GLP1Ra-preceding group, the annual change in eGFR and change in the logarithmic value of urine albumin-to-creatinine ratio (LnACR) was 0.27mL/min/1.73 m2/year [-0.60, 1.14], and 0.18 [-0.10, 0.43] respectively. LnACR at baseline, pioglitazone use, and baseline mean arterial blood pressure were independent factors for renal composite outcome with ORs [95% CI] of 1.15 [1.01, 1.31], 0.47 [0.23, 0.96], and 1.03 [1.01, 1.05], respectively. Conclusion: In combination therapy with SGLT2i and GLP1Ra, the difference in the preceding drug did not affect the renal composite outcome. Disclosure K.Kobayashi: None. M.Toyoda: None.

Editors' Note: Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke.

Editors' Note: Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke.

Author Response: Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke.

Author Response: Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke.