sglt-2 inhibitor

sglt - 2 抑制剂
  • 文章类型: Journal Article
    钠-葡萄糖协同转运蛋白-2(SGLT-2)抑制剂的实例是Empagliflozin。它是一种治疗2型糖尿病(T2DM)的新药,但是人们对依帕列净如何影响心脏的兴趣越来越大。本研究旨在研究依帕列净治疗对T2DM患者心室复极参数的影响。
    T2DM患者被纳入一项前瞻性研究。心室复极参数的测量,包括QT间隔,校正QT间期(QTc),QT离散度(QTd),Tpeak-to-Tendinterval(Tp-e),和校正QTc的Tpeak-to-Tend间隔(Tp-e/QTc),在开始empagliflozin治疗之前和治疗开始后六个月获得。进行统计分析以评估这些参数的变化。
    在这项研究中,177例患者中有95例被诊断为T2DM。在T2DM患者中,40为男性(42%),对照组为48%的男性(p=0.152)。2型糖尿病患者的平均年龄为60.2±9.0岁,对照组为58.2±9.2年(p=0.374)。当比较代表心室复极的参数的治疗前和治疗后测量值时(QT408.5±22.9/378.8±14.1,p<0.001;QTc427.0±20.5/404.7±13.8,p<0.001;QTd52.1±1.2/47.8±1.7,p<0.001;Tp-e82.3±8.7/67.1±5.1,p<0.001;Tp-e/QTc分别为0.19±观察到有统计学意义的改善。还观察到QTc参数变化幅度的统计学显着的剂量依赖性下降(19.4/29.6,p=0.038)。
    根据这些结果,依帕列净可降低潜在室性心律失常的风险.
    UNASSIGNED: An example of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor is Empagliflozin. It is a new medicine for treating type 2 diabetes mellitus (T2DM), but there is increasing interest in how empagliflozin affects the heart. This study aims to examine the impact of empagliflozin treatment on ventricular repolarization parameters in T2DM patients.
    UNASSIGNED: T2DM patients were included in a prospective study. Measurements of ventricular repolarization parameters, including QT interval, corrected QT interval (QTc), QT dispersion (QTd), Tpeak-to-Tend interval (Tp-e), and Tpeak-to-Tend interval corrected for QTc (Tp-e/QTc), were obtained before initiating empagliflozin treatment and six months following treatment initiation. Statistical analysis was performed to assess changes in these parameters.
    UNASSIGNED: In this study, 95 patients were diagnosed with T2DM out of 177 patients. Among T2DM patients, 40 were male (42%) compared to 48% males in controls (p = 0.152). The average age of the T2DM patients was 60.2 ± 9.0 years, compared to 58.2 ± 9.2 years in the control group (p = 0.374). When comparing pre- and post-treatment measurements of parameters representing ventricular repolarization (QT 408.5 ± 22.9/378.8 ± 14.1, p < 0.001; QTc 427.0 ± 20.5/404.7 ± 13.8, p < 0.001; QTd 52.1 ± 1.2/47.8 ± 1.7, p < 0.001; Tp-e 82.3 ± 8.7/67.1 ± 5.1, p < 0.001; Tp-e/QTc 0.19 ± 0.01/0.17 ± 0.01, p < 0.001 (respectively)), statistically significant improvements were observed. A statistically significant dose-dependent decline in the magnitude of change in the QTc parameter (19.4/29.6, p = 0.038) was also observed.
    UNASSIGNED: According to these results, empagliflozin may decrease the risk of potential ventricular arrhythmias.
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  • 文章类型: Case Reports
    BRASH(心动过缓,肾功能不全,房室结阻滞,震惊,和高钾血症)综合征是最近公认的临床过程,如果没有充分和及时的治疗,可能是致命的。因此,临床医生认识该综合征很重要。该病例显示了一名73岁的心力衰竭患者在服用达格列净后发生的BRASH综合征的例子,一种以前在文献中与这种现象无关的药物。鉴于钠-葡萄糖协同转运蛋白-2(SGLT-2)抑制剂的临床应用日益受到重视,处方者必须尊重潜在合并症患者的潜在副作用,并记住在开始这些药物治疗后重新评估肾功能的重要性.这里,我们回顾了BRASH的病理生理学,SGLT-2抑制剂的肾脏作用,以及在家中对患者进行容量管理和利尿剂剂量滴定教育的重要性。
    BRASH (bradycardia, renal dysfunction, atrioventricular node blockade, shock, and hyperkalemia) syndrome is a recently recognized clinical process that can be fatal if not adequately and promptly treated. As such, it is important for clinicians to recognize the syndrome. This case demonstrates an example of BRASH syndrome in a 73-year-old patient with heart failure occurring after initiation of dapagliflozin, a drug not previously associated with this phenomenon in the literature. Given the increasingly appreciated clinical utility of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, prescribers must respect their potential side effects in patients with underlying comorbidities and remember the importance of re-evaluating renal function after initiation of these medications. Here, we review the pathophysiology of BRASH, the renal effects of SGLT-2 inhibitors, and the importance of educating patients on volume management and diuretic dose titration at home.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    钠-葡萄糖协同转运蛋白-2抑制剂(SGLT-2抑制剂)治疗心力衰竭患者EF保留(HFpEF)的价值在EPPEROR保留试验之前是未知的。我们旨在评估哥伦比亚心力衰竭登记处(RECOLFACA)中有资格接受依帕列净治疗的HFpEF患者的比例。
    RECOLFACA在2017-2019年期间从哥伦比亚的60个医疗中心招募了诊断为HF的成年患者。EMPEROR保留试验的标准用于招募参与者。主要结局是符合N末端B型利钠肽前体(NT-proBNP)标准的个体资格,而次要结局是无NT-proBNP数据的合格性.
    RECOLFACA有799例HFpEF患者(平均年龄70.7±13.5;50.7%为男性)。根据EMPEROR保留试验的主要选择标准,当考虑NT-proBNP阈值时,73.7%的患者有资格接受依帕列净治疗。NT-proBNP阈值代表使用该生物标志物测量的患者不合格的主要决定因素(13.6%;n=16)。在没有NT-proBNP数据的患者中,排除的主要原因是诊断为有症状的低血压或收缩压低于100mmHg(7.5%),eGFR<20ml/min/1.73m2(4.3%),血红蛋白<9g/dl(3.1%)。排除NT-proBNP标准将empagliflozin合格性提高到80.6%。
    根据EMPEROR保留的试验标准,大多数来自RECOLFACA的HFpEF患者是开始依帕列净治疗的潜在候选者。这些发现有利于在日常医疗实践中使用SGLT-2抑制剂药物,这可以进一步降低HF患者的发病率和死亡率,不管他们的EF分类。
    UNASSIGNED: The value of Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitor) therapy in individuals with heart failure with preserved EF (HFpEF) was unknown until the EMPEROR-Preserved trial. We aimed to assess the proportion of patients with HFpEF that are eligible for empagliflozin therapy within the Colombian Heart Failure Registry (RECOLFACA).
    UNASSIGNED: RECOLFACA enrolled adult patients with a HF diagnosis during 2017-2019 from 60 medical centers in Colombia. Criteria of the EMPEROR-Preserved Trial were used to recruit participants. The main outcome was individual eligibility with N-terminal pro-B-type natriuretic peptide (NT-proBNP) criteria, while the secondary outcome was eligibility without NT-proBNP data.
    UNASSIGNED: RECOLFACA had 799 patients with HFpEF (mean age70.7 ± 13.5; 50.7 % males). According to the major selection criteria of the EMPEROR Preserved Trial, 73.7 % patients would be eligible for empagliflozin therapy initiation when considering the NT-proBNP threshold. The NT-proBNP threshold represented the main determinant of ineligibility in patients with this biomarker measure (13.6 %; n = 16). In patients without NT-proBNP data, the main reasons for exclusion were the diagnosis of symptomatic hypotension or a systolic blood pressure below 100 mmHg (7.5 %), having an eGFR < 20 ml/min/1.73 m2 (4.3 %), and haemoglobin < 9 g/dl (3.1 %). Excluding NT-proBNP criteria increased empagliflozin eligibility to 80.6 %.
    UNASSIGNED: Most patients with HFpEF from RECOLFACA are potential candidates for empagliflozin therapy initiation according to the EMPEROR-Preserved trial criteria. These findings favor the utilization of SGLT-2 inhibitor medications in daily medical practice, which may further decrease morbidity and mortality in HF patients, regardless of their EF classification.
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  • 文章类型: Case Reports
    顺铂,自1978年FDA批准用于睾丸癌以来广泛使用的化疗药物,与肾毒性和低镁血症有关。补充镁不仅是低镁血症的治疗方法,而且是预防顺铂引起的肾毒性(CIN)的公认药物。考虑到静脉使用镁,甚至补充口服形式的挑战,需要有效减少尿镁排泄的药物。阿米洛利和钠-葡萄糖协同转运蛋白2抑制剂(SGLT2抑制剂)已成为潜在的候选药物。阿米洛利是一种众所周知的保钾利尿剂,在临床前数据中也具有低镁血症作用。SGLT2抑制剂是最初用于糖尿病的一类药物,也被观察到对心血管死亡率有积极影响。糖尿病肾病,和低镁血症.在18项试验的荟萃分析研究中发现SGLT2抑制剂可降低低镁血症。然而,这些试验不是专门为评估低镁血症而设计的,它们目前在低镁血症中的使用被认为是标签外的。
    Cisplatin, a chemotherapy agent widely used since its FDA approval in 1978 for testicular cancer, is associated with nephrotoxicity and hypomagnesemia. Magnesium supplementation is not only a treatment for hypomagnesemia but also a well-established agent in preventing cisplatin-induced nephrotoxicity (CIN). Considering the challenges associated with intravenous magnesium use and even with the supplementation of oral forms, there is a need for drugs that effectively reduce urinary magnesium excretion. Amiloride and sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have emerged as potential candidates. Amiloride is a well-known potassium-sparing diuretic that also has a hypomagnesemia effect seen in preclinical data. SGLT2 inhibitors are a drug class initially used in diabetes that was also observed to have positive effects on cardiovascular mortality, diabetic kidney disease, and hypomagnesemia. SGLT2 inhibitors were found to reduce hypomagnesemia in a meta-analysis study of 18 trials. However, these trials were not specifically designed for the evaluation of hypomagnesemia, and their current use in hypomagnesemia is considered off-label.
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  • 文章类型: Case Reports
    急性胰腺炎是一种常见且可能危及生命的疾病。它的特点是胰腺发炎,最常导致血液中胰腺酶水平升高。在一部分患者中,然而,常规生物标志物水平可能保持在参考范围内。这种情况有可能给医疗保健专业人员带来诊断挑战,并可能导致误诊或延迟治疗。本文介绍了淀粉酶和脂肪酶正常的急性胰腺炎的有趣的临床情况,讨论了可能导致正常酶呈递的因素,并提醒临床医生注意急性胰腺炎的诊断标准,这不一定需要升高的胰腺酶。
    Acute pancreatitis is a common and potentially life-threatening condition. It is characterized by inflammation of the pancreas, most often leading to elevated levels of pancreatic enzymes in the blood. In a subset of patients, however, conventional biomarker levels may remain within the reference range. Such instances have the potential to create a diagnostic challenge for healthcare professionals and can lead to misdiagnosis or delayed treatment. This article presents the intriguing clinical scenario of acute pancreatitis with normal amylase and lipase, discusses factors that may lead to normoenzymatic presentation, and reminds clinicians of the diagnostic criteria for acute pancreatitis, which does not necessarily require elevated pancreatic enzymes.
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  • 文章类型: Journal Article
    背景和目的:本研究的目的是探讨不同的疗法如何调节胰岛素抵抗,无论是因果关系还是结果,影响初治T2DM受试者的代谢参数。受试者和方法:总共212名受试者被分配接受严格的日本饮食(n=65),吡格列酮的剂量范围为15-30毫克/天(n=70),或canagliflozin,剂量范围为50-100mg/天(n=77),持续三个月。研究了代谢参数相对于胰岛素抵抗的相关性和变化(Δ)。结果:在这些不同的治疗干预措施中,ΔHOMA-R与ΔFBG和ΔHOMA-B呈显著相关,同时证明与基线HOMA-R呈负相关。然而,其他参数,如ΔHbA1c,ΔBMI,ΔTC,ΔTG,Δnon-HDL-C,或ΔUA根据治疗方案显示不同的模式。根据ΔHOMA-R的中值将参与者分为两组:下半部分(X)和上半部分(Y)。在所有治疗中,与Y组相比,X组始终表现出更明显的FBG降低。而其他参数包括HbA1c,HOMA-B,TC,TG,HDL-C,非HDL-C,TG/HDL-C比值,或UA表现出不同的调节反应,这取决于所施用的治疗。结论:这些发现表明,(1)在这些治疗中观察到胰岛素抵抗的变化,以及(2)这些治疗对胰岛素抵抗的调节,无论是因果关系还是后果性的,结果对血糖参数的不同影响,β细胞功能,特定脂质,体重,或UA。
    Bacground and Objectives: The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naïve subjects with T2DM. Subjects and Methods: A total of 212 subjects were assigned to receive either a tight Japanese diet (n = 65), pioglitazone at doses ranging from 15-30 mg/day (n = 70), or canagliflozin at doses ranging from 50-100 mg/day (n = 77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. Results: Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered. Conclusions: These findings suggest that (1) regression to the mean is observed in the changes in insulin resistance across these therapies and (2) the modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight, or UA.
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  • 文章类型: Journal Article
    卡非佐米是一种不可逆的蛋白酶体抑制剂,用于多发性骨髓瘤患者。然而,卡非佐米治疗与心血管并发症有关。Empagliflozin,钠葡萄糖协同转运蛋白2抑制剂(SGLT-2)抑制剂,是一种口服抗糖尿病药物,具有抗氧化和抗炎特性。本研究的目的是确定依帕格列净对卡非佐米诱导的心脏毒性的心脏保护作用。C57BL/6小鼠随机分为四组:对照组,empagliflozin,Carfilzomib,和carfilzomib+empagliflozin。Empagliflozin通过改善组织学改变来预防卡非佐米诱导的心脏毒性,CK-MB,和肌钙蛋白-I此外,它通过对过氧化氢酶活性的作用抑制卡非佐米诱导的氧化损伤和炎症,降低谷胱甘肽水平和超氧化物歧化酶活性,和降低核因子-κB(p65)和细胞因子水平。机械上,empagliflozin消除了卡非佐米诱导的内质网应激,如通过对葡萄糖调节蛋白-78(GRP-78)/活化转录因子6(ATF6)/C/EBP同源蛋白(CHOP)轴的作用所证明的。有趣的是,卡非佐米显著诱导自噬,empagliflozin进一步增强了这种效果,LC3B和beclin-1mRNA表达增加,p62表达减少。通过降低活性caspase-3的表达证实了依帕格列净对细胞凋亡的影响。重要的是,依帕列净未改变卡非佐米对人U266B1多发性骨髓瘤细胞的细胞毒作用.我们的研究结果表明,empagliflozin可能为减轻多发性骨髓瘤患者卡非佐米引起的心脏毒性提供一种新的治疗策略.
    Carfilzomib is an irreversible proteasome inhibitor used for multiple myeloma patients. However, carfilzomib treatment is associated with cardiovascular complications. Empagliflozin, an Sodium Glucose Co-transporter 2 inhibitor (SGLT-2) inhibitor, is an oral antidiabetic drug with proven antioxidant and anti-inflammatory properties. The aim of the present study was to determine the cardioprotective effects of empagliflozin against carfilzomib-induced cardiotoxicity. C57BL/6 mice were randomly divided into four groups: control, empagliflozin, carfilzomib, and carfilzomib + empagliflozin. Empagliflozin prevented carfilzomib-induced cardiotoxicity by ameliorating histological alterations, CK-MB, and troponin-I. Moreover, it inhibited carfilzomib-induced oxidative damage and inflammation via its action on catalase activity, reduced glutathione levels and superoxide dismutase activity, and reduced nuclear factor-κB (p65) and cytokine levels. Mechanistically, empagliflozin abrogated endoplasmic reticulum stress induced by carfilzomib, as evidenced by the effect on the Glucose Regulated Protein-78 (GRP-78)/Activating Transcription Factor 6 (ATF6)/C/EBP homologous protein (CHOP) axis. Intriguingly, carfilzomib significantly induced autophagy, an effect that was further enhanced by empagliflozin, evidenced by increased LC3B and beclin-1 mRNA expression and reduced p62 expression. The effect of empagliflozin on apoptosis was confirmed by reduced expression of active caspase-3. Importantly, empagliflozin did not alter the cytotoxic effect of carfilzomib on human U266B1 multiple myeloma cells. our findings suggest that empagliflozin may provide a new therapeutic strategy to mitigate carfilzomib-induced cardiotoxicity in multiple myeloma patients.
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  • 文章类型: Journal Article
    动脉粥样硬化性心血管疾病(ASCVD)仍然是全球主要的死亡原因之一,冠状动脉疾病(CAD)是ASCVD的最常见形式。2型糖尿病(DM)患者在病程中发生ASCVD的风险增加,CAD是受影响个体中最常见的死亡原因,导致幸存者的预期寿命缩短和发病率增加。最近,2类新型抗糖尿病药物,即钠-葡萄糖共转运蛋白-2(SGLT-2)抑制剂和胰高血糖素样肽-1(GLP-1)受体激动剂,对2型糖尿病患者显示出令人印象深刻的心肾益处,即使在没有基线DM的情况下,它们也可能降低心肾风险。然而,迄今为止,尚无证据证明其在急性冠脉综合征(ACS)事件中的安全性和有效性,无论是否伴随DM。本研究旨在提供详细的,关于SGLT-2抑制剂和GLP-1受体激动剂在ACS中的潜在作用的现有临床证据的最新介绍,并强调这些药物类别是否可以在这一特定患者群体中用作标准治疗的辅助手段,以及潜在的短期和长期心血管益处的介绍。
    Atherosclerotic Cardiovascular Disease (ASCVD) is still one of the leading causes of death globally, with Coronary Artery Disease (CAD) being the most prevalent form of ASCVD. Patients with type 2 Diabetes Mellitus (DM) experience an increased risk for ASCVD during the disease course, with CAD being the most common cause of death among affected individuals, resulting in shorter life expectancy and increased morbidity among survivors. Recently, 2 novel classes of anti-diabetic drugs, namely Sodium-Glucose co-Transporter-2 (SGLT-2) inhibitors and Glucagon-Like Peptide-1 (GLP-1) receptor agonists, have shown impressive cardio-renal benefits for patients with type 2 DM, while they might decrease cardio-renal risk even in the absence of baseline DM. However, there is no evidence to date regarding their safety and efficacy in the setting of an acute coronary syndrome (ACS) event, regardless of concomitant DM. This study aims to provide a detailed, updated presentation of currently available clinical evidence concerning the potential role of SGLT-2 inhibitors and GLP-1 receptor agonists in the setting of an ACS, and to highlight whether those drug classes could be utilized as adjuncts to standard-of-care treatment in this specific patient population, along with a presentation of the potential short- and long-term cardiovascular benefits.
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  • 文章类型: Journal Article
    2型糖尿病(T2DM)与抑郁症之间的关系是医学关注的重要领域,2型糖尿病患者的抑郁症发生率高于普通人群。这种联系不仅在糖尿病患者抑郁症状的患病率上得到了证明,而且在这些症状影响糖尿病管理的方式上也得到了证明。此外,抗糖尿病药物的影响,特别是钠-葡萄糖协同转运蛋白-2(SGLT2)抑制剂,关于抑郁风险是一个正在进行的研究主题,与二甲双胍和吡格列酮等药物的作用形成对比。本研究旨在全面分析T2DM与抑郁的关系,关注糖尿病患者抑郁症状的患病率,以及抗糖尿病药物在调节抑郁风险中的作用。方法利用国家健康和营养调查(NHANES)的数据,我们关注的是T2DM患者。使用九项患者健康问卷(PHQ-9)评估抑郁状态,评估抑郁症状的有效工具。参与者的抑郁状态根据PHQ-9综合评分进行分类。分析包括人口统计学变量和抗糖尿病药物的使用,专注于SGLT2抑制剂。经年龄调整的Logistic回归模型,种族/民族,BMI被采用。结果我们的研究涉及23,575名参与者,其中7,862人患有T2DM。糖尿病组和非糖尿病组之间的年龄和BMI存在显着差异。Logistic回归分析表明,与未使用SGLT2抑制剂的糖尿病患者相比,非糖尿病个体患抑郁症的可能性显着降低。然而,在服用SGLT2抑制剂的糖尿病患者和未服用这些药物的糖尿病患者之间,抑郁水平无统计学差异.结论这些发现突出了糖尿病之间的复杂关系,抗糖尿病药物,和抑郁症。值得注意的是,我们发现SGLT2抑制剂对糖尿病患者的抑郁症没有显著影响,挑战先前关于特定抗糖尿病药物在心理健康中的作用的假设。我们还发现,老年糖尿病患者的抑郁症状报告较少,提示心理社会因素的影响以及需要针对特定年龄的抑郁症管理策略。这项研究强调了进一步研究的必要性,以探索不同的抗糖尿病药物对心理健康结果的细微差别影响。针对T2DM心理健康挑战的更个性化治疗方法。
    The relationship between type 2 diabetes mellitus (T2DM) and depression presents a significant area of medical concern, characterized by a higher incidence of depression among T2DM patients compared to the general population. This connection is not only evidenced in the prevalence of depressive symptoms in diabetic patients but also in the way these symptoms impact diabetes management. Furthermore, the influence of antidiabetic medications, especially sodium-glucose cotransporter-2 (SGLT2) inhibitors, on depression risk is a topic of ongoing research, with contrasting findings regarding the effects of drugs like metformin and pioglitazone. The aim of this study is to provide a comprehensive analysis of the relationship between T2DM and depression, focusing on the prevalence of depressive symptoms among diabetic patients, and the role of antidiabetic medications in modulating depression risk. Methods Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we focused on individuals with T2DM. Depression status was assessed using the nine-item Patient Health Questionnaire (PHQ-9), a validated tool for evaluating depressive symptoms. Participants\' depression status was categorized based on PHQ-9 composite scores. The analysis included demographic variables and the use of antidiabetic medications, with a focus on SGLT2 inhibitors. Logistic regression models adjusted for age, race/ethnicity, and BMI were employed. Results Our study involved 23,575 participants, of which 7,862 had T2DM. A significant difference in age and BMI was observed between diabetic and non-diabetic groups. Logistic regression analysis indicated that non-diabetic individuals had a significantly lower likelihood of depression compared to diabetic patients not on SGLT2 inhibitors. However, no statistically significant difference in depression levels was found between diabetic patients on SGLT2 inhibitors and those not on these medications. Conclusion These findings highlight the complex relationship between diabetes, antidiabetic medication, and depression. Notably, we found no significant impact of SGLT2 inhibitors on depression in diabetic patients, challenging previous assumptions about the role of specific antidiabetic drugs in mental health. We also revealed that older diabetic individuals reported fewer depressive symptoms, suggesting the influence of psychosocial factors and the need for age-specific depression management strategies. This research underscores the necessity of further studies to explore the nuanced effects of different antidiabetic medications on mental health outcomes, guiding toward more personalized treatment approaches for the mental health challenges in T2DM.
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