RESUMO
Background: No comprehensive meta-analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta-analysis fills this gap in knowledge. Methods: A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Results: Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD -0.62%, 95% CI [-0.80, -0.44], p < 0.00001, I 2 = 91%) and 15 mg (MD -0.69%, 95% CI [-0.91, -0.47], p < 0.00001, I 2 = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Conclusion: Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Trial Registration: Registration number: CRD42023456450.
Assuntos
Glicemia , Compostos Bicíclicos Heterocíclicos com Pontes , Diabetes Mellitus Tipo 2 , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Resultado do Tratamento , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemia/induzido quimicamenteRESUMO
Although sodium-glucose transport protein-2 (SGLT2) inhibitors (SGLT2i) do not increase the risk of acute kidney injury (AKI) in general, they may pose a risk in patients undergoing angiography. This prospective cohort study aimed to evaluate the safety and efficacy of SGLT2i for post-contrast AKI (PC-AKI) in patients with type 2 diabetes mellitus (T2DM). Following screening, 306 patients with T2DM selected to undergo coronary arterial angiography with or without percutaneous intervention were enrolled. Patients were divided into the SGLT2i exposure and non-exposure groups. The primary outcome was PC-AKI, defined as an increase in serum creatinine levels > 0.5 mg/dL (44.2 µmol/L), or 25% above the baseline, within 48-72 h after exposure to contrast medium. The incidence of PC-AKI in the overall T2DM population was 5.2% (16/306). Following 1:1 propensity score matching, the incidence of PC-AKI was significantly higher in the SGLT2i group than in the non-SGLT2i group (10.7% vs. 2.9%; P = 0.027), with an odds ratio of 4.5 (95% confidence interval: 1.0-20.2; P = 0.047). Furthermore, PC-AKI occurred at a higher rate among short-term users of SGLT2i than long-term users (20.5% vs. 3.4%, P = 0.018). Thus, our findings suggest an increased risk of PC-AKI associated with short-term SGLT2i therapy in patients with T2DM.
Assuntos
Injúria Renal Aguda , Meios de Contraste , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Injúria Renal Aguda/induzido quimicamente , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Meios de Contraste/efeitos adversos , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Angiografia Coronária/efeitos adversos , Creatinina/sangue , Incidência , Fatores de RiscoRESUMO
This report addresses evidence for efficacy of diabetes medications with a focus on stroke risk reduction. The cardiovascular benefits of SGLT-2 inhibitors and GLP-1 receptor agonists have been well-established; however, clinical trials to date have examined composite cardiovascular endpoints that include, but do not specifically focus on, stroke. The purpose of this case review is to examine the evidence for the various diabetes medications in reducing the risk for stroke. This literature review was inspired by a patient seen in a geriatric day hospital program with diabetes and a history of multiple strokes. Our goal was to select a diabetes management regimen that would provide both glycemic control and stroke risk reduction. As diabetes and cerebrovascular disease commonly coexist and are important contributors to morbidity and mortality in older individuals, appropriate management must incorporate both current evidence as well as consideration for patient-specific factors that may influence the treatment plan. This patient case illustrates the importance of both.
Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Prevenção Secundária , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Hipoglicemiantes/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Prevenção Secundária/métodos , Idoso de 80 Anos ou mais , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , FemininoRESUMO
OBJECTIVES: The objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet. METHODS: In this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured. RESULTS: The EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (- 8.92 ± 1.80 vs. - 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05). CONCLUSION: In non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run. LEVEL I: Randomized clinical trial.
Assuntos
Compostos Benzidrílicos , Restrição Calórica , Glucosídeos , Obesidade , Sobrepeso , Topiramato , Humanos , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Masculino , Feminino , Adulto , Obesidade/tratamento farmacológico , Obesidade/dietoterapia , Obesidade/complicações , Sobrepeso/tratamento farmacológico , Sobrepeso/dietoterapia , Topiramato/uso terapêutico , Pessoa de Meia-Idade , Índice de Massa Corporal , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Quimioterapia Combinada , Método Duplo-Cego , Fármacos Antiobesidade/uso terapêutico , Composição Corporal/efeitos dos fármacos , Circunferência da Cintura/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoAssuntos
Compostos Benzidrílicos , Quimioterapia Combinada , Glucosídeos , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Masculino , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Idoso , Pessoa de Meia-Idade , Antagonistas dos Receptores de Endotelina/uso terapêutico , Antagonistas dos Receptores de Endotelina/administração & dosagem , Antagonistas do Receptor de Endotelina A/uso terapêutico , Antagonistas do Receptor de Endotelina A/administração & dosagemRESUMO
CLINICAL QUESTION: What is the impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on survival and on cardiovascular and kidneyoutcomes for adults living with chronic kidney disease (CKD)? CURRENT PRACTICE: Few therapies slow kidney disease progression and improve long term prognosis for adults living with CKD. SGLT-2 inhibitors have demonstrated cardiovascular and kidney benefits in adults with CKD with and without type 2 diabetes. Existing guidance for SGLT-2 inhibitors does not account for the totality of current best evidence for adults with CKD and does not provide fully stratified treatment effects and recommendations across all risk groups based on risk of CKD progression and complications. RECOMMENDATIONS: The guideline panel considered evidence regarding benefits and harms of SGLT-2 inhibitor therapy for adults with CKD over a five year period, along with contextual factors, and provided the following recommendations:1. For adults at low risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)2. For adults at moderate risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)3. For adults at high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour)4. For adults at very high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour).Recommendations are applicable to all adults with CKD, irrespective of type 2 diabetes status. HOW THIS GUIDELINE WAS CREATED: An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified typical risk strata of adults with CKD (from low to very high risk of CKD progression and related complications) using the classification system developed by Kidney Disease Improving Global Outcomes (KDIGO), and applied an individual patient perspective in moving from evidence to recommendations. Effects of SGLT-2 inhibitors were interpreted in absolute terms applicable to different risk strata with varying baseline risks for outcomes of benefit over a five year period. The panel explicitly considered the balance of benefits, harms, and burdens of starting an SGLT-2 inhibitor, incorporating the values and preferences of adults with different risk profiles. Interactive evidence summaries and decision aids accompany multilayered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that allows reuse and adaptation. THE EVIDENCE: A linked systematic review and pairwise meta-analysis (13 trials including 29 614 participants) of benefits and harms associated with SGLT-2 inhibitors in adults with CKD with or without type 2 diabetes informed guidance. Among individuals at very high risk of CKD progression and complications, moderate to high certainty evidence shows SGLT-2 inhibitors (relative to placebo or standard care without SGLT-2 inhibitors) decrease all-cause and cardiovascular mortality, hospitalisation for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke. Among individuals at high risk, moderate to high certainty evidence shows SGLT-2 inhibitors result in similar benefits across outcomes except demonstrating little or no effect on hospitalisation for heart failure and kidney failure. Among individuals at moderate and low risk, moderate to high certainty evidence shows SGLT-2 inhibitors probably reduce all-cause mortality and non-fatal stroke, with little or no effect for other outcomes of benefit. Risk-stratified estimates were unavailable for outcomes of harm; the panel therefore considered absolute effects summarised across risk strata. SGLT-2 inhibitors are associated with little or no effect on acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolaemia, although a residual possibility of harms at the individual patient level remains. UNDERSTANDING THE RECOMMENDATION: In order to apply recommendations, clinicians must appropriately identify adults with CKD, consider the underlying aetiology, and risk stratify them based on glomerular filtration rate (estimated or measured) and degree of albuminuria. In addition to classifying individuals into risk strata, further estimation of a given patient's risk based on the extent of their kidney disease and other comorbidities may be warranted to inform individual-level decisions and shared decision making. Available risk calculators may help estimate a given patient's risk of CKD progression and complications.
Assuntos
Diabetes Mellitus Tipo 2 , Progressão da Doença , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Insuficiência Renal Crônica/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Adulto , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controleRESUMO
OBJECTIVE: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of drugs that lower blood glucose and reduce mortality in heart failure patients with reduced ejection fraction (HFrEF). They also have antioxidant effects. The exact mechanism of SGLT-2i is unknown. This study investigated the effects of SGLT-2i on asprosin, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP-1) concentrations and echocardiographic measurements of strain in the left heart chamber. PATIENTS AND METHODS: This prospective follow-up study included 56 patients with HFrEF and diabetes mellitus (DM) who did not initially receive SGLT-2 inhibitors. The control group consisted of 30 healthy individuals. Patients with HFrEF were administered either empagliflozin (n=28) or dapagliflozin (n=28) in addition to their treatment. The patient group was evaluated for left ventricular global longitudinal strain (LVGLS), left atrial (LA) strain, and LA volumes at the beginning and third month of the study. The control group had blood collected once, while the patient group had it twice: at the start of the trial, on the same day as the echocardiographic evaluation, and at the end of the third month after starting an SGLT-2i. Serum levels of asprosin, MMP-1 and TIMP-1 were assessed. RESULTS: LVGLS increased significantly in HFrEF patients at the third-month assessment compared to baseline (-8.6±2.3% vs. -9±2.5%, respectively; p<0.001), but there was no significant difference in LVEF (p=0.593). A substantial increase was observed in the left atrial ejection fraction (LAEF) compared to baseline values (36.3±9.4% vs. 42.1±8.7%, respectively; p<0.001), driven by a reduction in minimal LA volume [32.5 (19-96) ml vs. 32 (20-86) ml, respectively; p=0.018]. Compared to baseline evaluation, LA reservoir [13 (6-25) vs. 16.5 (2-26), respectively; p<0.001] and contraction strain (7.7±4.3 vs. 9.4±5.6, respectively; p=0.014) values were also enhanced at the third month. Between the baseline and the 3rd month, the patient group's LA conduit strain (p=0.122) and LA maximum volume (p=0.716) remained unchanged. Serum asprosin significantly increased (11.7±5.1 ng/mL vs. 14±9.4 ng/mL, respectively; p=0.032); however, no statistically significant alteration was detected in MMP (p=0.278) and TIMP-1 levels (p=0.401). CONCLUSIONS: SGLT-2i are associated with elevated levels of LVGLS, LAEF, LA contraction strain, and LA reservoir strain. SGLT-2i medications may improve plasma asprosin levels to boost energy metabolism, reduce oxidative stress and reactive oxygen radicals.
Assuntos
Antioxidantes , Ecocardiografia , Glucosídeos , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Volume Sistólico , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Glucosídeos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Estudos Prospectivos , Idoso , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Seguimentos , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown. OBJECTIVES: These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status. METHODS: SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular death. Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) score was a prespecified secondary endpoint. This analysis evaluated change in the KCCQ-12 score from baseline to month 4. RESULTS: Of 1,222 patients randomized, 1,113 (91%) had complete KCCQ-12 data at baseline and 4 months. The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups. Sotagliflozin vs placebo reduced the risk of the primary endpoint consistently across KCCQ-12 tertiles (Ptrend = 0.54). Sotagliflozin-treated patients vs those receiving placebo experienced modest improvement in KCCQ-12 at 4 months (adjusted mean change: 4.1 points; 95% CI: 1.3-7.0 points; P = 0.005). KCCQ-12 improvements were consistent across prespecified subgroups, including left ventricular ejection fraction <50% or ≥50%. More patients receiving sotagliflozin vs those receiving placebo had at least small (≥5 points) improvements in KCCQ-12 at 4 months (OR: 1.38; 95% CI: 1.06-1.80; P = 0.017). CONCLUSIONS: Sotagliflozin improved symptoms, physical limitations, and quality of life within 4 months after worsening HF, with consistent benefits across baseline demographic and clinical characteristics. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).
Assuntos
Diabetes Mellitus Tipo 2 , Glicosídeos , Nível de Saúde , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Masculino , Feminino , Glicosídeos/uso terapêutico , Idoso , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Progressão da Doença , Volume Sistólico/efeitos dos fármacos , Qualidade de VidaAssuntos
Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Nível de Saúde , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Progressão da DoençaRESUMO
Background: Sodiumâglucose cotransporter-2 (SGLT2) inhibitors offer glycaemic and cardiorenal benefits in the early stage of chronic kidney disease (CKD). However, the use of SGLT2 inhibitors may increase the risk of genitourinary tract infection (GUTI). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may also cause deterioration of kidney function. The long-term follow-up of cardiorenal outcomes and GUTI incidence in patients with advanced CKD receiving SGLT2 inhibitors combined with ACEIs/ARBs should be further investigated. Methods: We analysed data from 5,503 patients in Taiwan's Taipei Medical University Research Database (2016-2020) who were part of a pre-end-stage renal disease (ESRD) program (CKD stages 3-5) and received ACEIs/ARBs. SGLT2 inhibitor users were matched 1:4 with nonusers on the basis of sex, CKD, and program entry duration. Results: The final cohort included 205 SGLT2 inhibitor users and 820 nonusers. SGLT2 inhibitor users experienced a significant reduction in ESRD/dialysis risk (aHR = 0.35, 95% CI = 0.190.67), and SGLT2 inhibitor use was not significantly associated with acute kidney injury or acute kidney disease risk. Among SGLT2 inhibitor users, those with a history of cardiovascular disease (CVD) had greater CVD rates. Conversely, those without a CVD history had lower rates of congestive heart failure, arrhythmia, acute pulmonary oedema, and acute myocardial infarction, although the differences were not statistically significant. Notably, SGLT2 inhibitor usage was associated with a greater GUTI incidence (aHR = 1.78, 95% CI = 1.122.84) shortly after initiation, irrespective of prior GUTI history status. Conclusion: Among patients with CKD stages 3-5, SGLT2 inhibitor use was linked to increased GUTI incidence, but it also significantly reduced the ESRD/dialysis risk without an episodic AKI or AKD risk. Clinical physicians should consider a personalized medicine approach by balancing GUTI episodes and cardiorenal outcomes for advanced CKD patients receiving SGLT2 inhibitors.
Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Taiwan/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Incidência , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologiaAssuntos
Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipolipemiantes , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipolipemiantes/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controleAssuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Glucosídeos , Hipoglicemiantes , Metformina , Fosfato de Sitagliptina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Metformina/uso terapêutico , Metformina/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Fosfato de Sitagliptina/uso terapêutico , Fosfato de Sitagliptina/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Resultado do Tratamento , Masculino , Feminino , Pessoa de Meia-Idade , Glicemia/análise , Hemoglobinas Glicadas/análise , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , IdosoAssuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Glucosídeos , Hipoglicemiantes , Metformina , Fosfato de Sitagliptina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Metformina/uso terapêutico , Metformina/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Fosfato de Sitagliptina/uso terapêutico , Fosfato de Sitagliptina/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Resultado do Tratamento , Masculino , Feminino , Pessoa de Meia-Idade , Glicemia/análise , Hemoglobinas Glicadas/análise , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , IdosoAssuntos
Arritmias Cardíacas , Inibidores do Transportador 2 de Sódio-Glicose , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Humanos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversosAssuntos
Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Resultado do Tratamento , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Risco , Animais , Transportador 2 de Glucose-Sódio/metabolismoRESUMO
BACKGROUND: Chronic brain dyscirculation is one of the frequent type 2 diabetes mellitus (DM) complications and leads to patients' disability. Sodium-glucose co-transporter type 2 inhibitors (SGLT-2i) have been proven to have advantages for cardiovascular system, but their effect on the central nervous system (CNS) has not been studied enough. AIM: To study empagliflozin effect on CNS damage functional and laboratory parameters in patients with type 2 DM and, under experimental conditions, to investigate the mechanisms of the drug neurotropic effect. MATERIALS AND METHODS: The clinical part of the study included patients with type 2 DM on metformin monotherapy (n=39). Patients with a target glycated hemoglobin level formed the "MET" group (n=19), in patients with a non-target glycated hemoglobin level empagliflozin was co-administered for the following 6 months (the "MET+EMPA" group, n=20). Healthy volunteers comprised the control group (n=16). The cognitive status and neuron-specific enolase (NSE) and neurofilament light chains (NLC) concentration were studied. DM was modeled in rats, thereafter the rats were treated with empagliflozin for 8 weeks. Microglia activation was assessed using anti-Iba-1 antibodies and morphological changes in neurons when stained by the Nissl method. RESULTS: Both in the "MET+EMPA" and the "MET" groups cognitive deficits were observed, according to the Montreal Cognitive Assessment (MOCA) (24.0 (23.0; 27.0) and 25.0 (21.0; 27.0) points) and the Mini-Mental State Examination (MMSE) (23.75 (23.0; 27.0) and 25.0 (21.0; 27.0) points). Empagliflozin therapy led to the cognitive status normalization after 6 months (26.5 (24.0; 27.0) points according to the MOCA scale and 27.5 (24.0; 28.0) points according to the MMSE). Initially, all patients had a significant increase of NSE (3.60 (2.66; 3.76) ng/ml in the "MET" group, 3.22 (2.94; 3.54) ng/ml in the "MET+EMPA¼ group, 2.72 (2.13; 2.72) ng/ml in the «Control¼ group) and NLC (4.50 (3.31; 5.56) ng/ml in the «MET¼ group, 5, 25 (3.75; 6.25) ng/ml in the «MET+EMPA¼ group comparing with 3.50 (2.25; 3.50) ng/ml in the «Control¼ group). Empagliflozin therapy led to a significant decrease in NLC already after 3 months (3.80 (3.25; 3.87) ng/ml), without significant influence on the NSE level. In the experiment, DM was characterized by an increased number of activated microgliocytes and destructured neurons and a decreased number of neurons with a normal structure. Empagliflozin therapy was accompanied by a decrease in the number of immunopositive microgliocytes in the CA1 zone of the hippocampus and an increase in the number of structured neurons. CONCLUSION: Type 2 diabetes mellitus is characterized by functional and biochemical changes in the central nervous system even under satisfactory glycemic control. Therapy with empagliflozin has a neuroprotective effect, manifested in an improvement in cognitive status and a decrease in NLC level. Empagliflozin reduces neuronal damage and abnormal microglial activation.
Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Ratos , Animais , Masculino , Feminino , Pessoa de Meia-Idade , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismoRESUMO
BACKGROUND: The overall mortality and morbidity benefit in patients with heart failure with a reduced ejection fraction is greatest with a treatment combination of sacubitril/valsartan, beta-blockers, mineralocorticoid-receptor antagonists, and sodium-glucose transporter-2 inhibitors, termed the "fantastic four" or "quadruple therapy." The addition of vericiguat (an oral soluble guanylate cyclase stimulator) is believed to aid in managing worsening heart failure after quadruple therapy. Among childhood and young adult cancer survivors, cardiovascular complications that develop more than 10 years after anthracycline-based chemotherapy have a poor prognosis. Therefore, this study reports the efficacy of multidrug regimen based on quadruple therapy for worsening heart failure in cancer survivors with anthracycline-induced cardiomyopathy. CASE PRESENTATION: A survivor of cancer as a young adult who received high-dose anthracycline chemotherapy presented with acute decompensated heart failure 20 years post-chemotherapy and worsening heart failure 1.5 years after discharge. The patient showed signs of improvement after a step-wise introduction of carvedilol, empagliflozin, sacubitril/valsartan, ivabradine, and spironolactone for worsening heart failure. Vericiguat was accelerated owing to the risk of more severe cardiovascular events associated with ongoing aortic stenosis and the poor prognosis of anthracycline-induced cardiomyopathy. Heart failure symptoms continued to improve, with significant cardiac reverse remodeling, and the patient successfully underwent aortic valve replacement for severe aortic stenosis. CONCLUSIONS: Our case highlighted that multidrug treatment with add-on vericiguat and ivabradine based on quadruple therapy can potentially treat worsening heart failure in young adult cancer survivors with severe anthracycline-induced cardiomyopathy.
Assuntos
Aminobutiratos , Antraciclinas , Compostos de Bifenilo , Sobreviventes de Câncer , Cardiomiopatias , Cardiotoxicidade , Combinação de Medicamentos , Quimioterapia Combinada , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Aminobutiratos/efeitos adversos , Aminobutiratos/uso terapêutico , Antraciclinas/efeitos adversos , Resultado do Tratamento , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/fisiopatologia , Cardiomiopatias/diagnóstico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Masculino , Antagonistas Adrenérgicos beta/uso terapêutico , Progressão da Doença , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Valsartana , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem , AdultoRESUMO
Sodium-glucose cotransporter-2 (SGLT-2) is expressed in the kidney and may contribute to anaemia and cardiovascular diseases. The effect of SGLT-2 inhibition on anaemia and vascular endpoints in sickle cell disease (SCD) is unknown. A murine model of SCD was studied to determine the effects of the SGLT-2 inhibitor, empagliflozin, on anaemia and stroke size. The University of Michigan's Precision Health Database was used to evaluate the effect of SGLT-2 inhibitors on anaemia in humans with SCD. SCD mice treated with daily empagliflozin for 8 weeks demonstrated increases in haemoglobin, haematocrit, erythrocyte counts, reticulocyte percentage and erythropoietin compared to vehicle-treated mice. Following photochemical-induced thrombosis of the middle cerebral artery, mice treated with empagliflozin demonstrated reduced stroke size compared to vehicle treated mice. In the electronic health records analysis, haemoglobin, haematocrit and erythrocyte counts increased in human SCD subjects treated with an SGLT-2 inhibitor. SGLT-2 inhibitor treatment of humans and mice with SCD is associated with improvement in anaemic parameters. Empagliflozin treatment is also associated with reduced stroke size in SCD mice suggesting SGLT-2 inhibitor treatment may be beneficial with regard to both anaemia and vascular complications in SCD patients.
Assuntos
Anemia Falciforme , Anemia , Compostos Benzidrílicos , Modelos Animais de Doenças , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Acidente Vascular Cerebral , Animais , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/sangue , Anemia Falciforme/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Humanos , Camundongos , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Masculino , Anemia/tratamento farmacológico , Anemia/etiologia , Feminino , Transportador 2 de Glucose-Sódio/metabolismo , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2 diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2 diabetes, with a specific focus on stratifying people by their frailty status. METHODS: In this retrospective, nationwide, longitudinal study, we identified people (aged ≥20 years) with type 2 diabetes who newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017 to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1 year before the index date. Mortality data were collected from the Taiwan National Death Registry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model. FINDINGS: We identified 320 210 people with type 2 diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57·7 years [SD 13·9], 11 338 [49·4%] were female, and 11 630 [50·6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58·8 years [12·3], 107 988 [42·0%] were female, and 149 207 [58·0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414 pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except for a higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than with SGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1·25 [95% CI 1·13-1·38]; p<0·0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2·43 [1·82-3·23]; p<0·0001), mild frailty (3·93 [3·03 -5·09]; p<0·0001), and moderate or severe frailty (2·60 [2·03-3·31]; p<0·0001) subgroups. INTERPRETATION: Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2 diabetes. FUNDING: Ministry of Education, Taiwan.