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1.
Medicine (Baltimore) ; 100(6): e24593, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578559

RESUMEN

BACKGROUND: The goals of improving quality of life and increasing longevity are receiving growing amounts of attention. Body weight and lipid metabolism are closely related to various complications of diabetes. The aim of this study was to rank SGLT inhibitors according to their efficacy with regard to weight and evaluate the effect of SGLT inhibitors on lipid metabolism at 24 weeks of treatment. METHODS: The Web of Science, PubMed, Cochrane Library, Embase, and Clinical Trials databases were electronically searched to collect randomized controlled trials involving patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the selected studies and extracted the outcome indexes. ADDIS 1.16.5 and STATA 16 software were used to perform the network meta-analysis and draw the plots. RESULTS: Ultimately, 36 studies were selected and included in this study. We found that all SGLT inhibitors were effective at reducing weight; canagliflozin was the most effective. SGLT inhibitors and placebo were not associated with significantly different serum cholesterol levels. SGLT inhibitors lowered serum triglyceride levels and increased serum high-density and low-density lipoprotein cholesterol levels. SGLT inhibitors also reduced the level of alanine aminotransferase. CONCLUSIONS: SGLT inhibitors can bring about weight loss in patients with T2DM and can also improve lipid metabolism. Therefore, patients with hyperlipidemia who have been unsuccessful at losing weight should consider taking SGLT inhibitors. In addition, SGLT inhibitors are hepatoprotective and appear to be safe for patients with mild to moderate liver dysfunction. TRIAL REGISTRATION: CRD42020198516.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Peso Corporal/efectos de los fármacos , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología
2.
BMJ ; 372: m4573, 2021 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-33441402

RESUMEN

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Mortalidad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Humanos , Hipoglucemiantes/efectos adversos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal/epidemiología , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos
3.
Medicine (Baltimore) ; 100(1): e24101, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33429775

RESUMEN

BACKGROUND: To evaluate dapagliflozin, canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin according to their effect on the glycated hemoglobin A1c (HbA1c) level in patients with type 2 diabetes mellitus. METHODS: The Web of Science, PubMed, Cochrane Library, EMBASE, and Clinical Trials databases were electronically searched to collect randomized controlled trials of patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used to perform the meta-analysis and to create plots. RESULTS: Finally, 27 studies were selected and included in this study. The meta-analysis results showed that sodium-dependent glucose transporter (SGLT) inhibitors significantly reduced the HbA1c level in patients with type 2 diabetes mellitus. However, these results were highly heterogeneous, so we conducted a subgroup analysis. The results of the subgroup analysis suggested that by dividing populations into different subgroups, the heterogeneity of each group could be reduced. CONCLUSIONS: SGLT inhibitors had a good effect on the HbA1c level in patients with type 2 diabetes mellitus, but there might be differences in the efficacy of SGLT inhibitors in different populations. It is hoped that more studies will be conducted to evaluate the efficacy and safety of SGLT inhibitors in different populations. REGISTRATION NUMBER: CRD42020185025.


Asunto(s)
Hemoglobina A Glucada/análisis , Inhibidores del Cotransportador de Sodio-Glucosa 2/normas , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/normas , Compuestos de Bencidrilo/uso terapéutico , Glucemia/análisis , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/normas , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Canagliflozina/farmacología , Canagliflozina/normas , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/farmacología , Glucósidos/normas , Glucósidos/uso terapéutico , Glicósidos/farmacología , Glicósidos/normas , Glicósidos/uso terapéutico , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Factores de Tiempo
4.
Rev Med Suisse ; 17(723): 188-191, 2021 Jan 27.
Artículo en Francés | MEDLINE | ID: mdl-33507658

RESUMEN

Diabetes is a rapidly evolving discipline, numerous new molecules and recommendations are available. However, these rapid changes are sometimes difficult to follow for general practitioners. Metformin remains the cornerstone of type 2 diabetes treatment after lifestyle modifications, which should always be encouraged before medications. Currently, the best classes to add after metformin seem to be SGLT2 inhibitors and GLP-1 receptor agonists, as these molecules showed some cardiovascular and renal beneficial effects in dedicated studies. Nevertheless, the current pharmacological plethora is paradoxically associated with clinical inertia as general practitioners may be in trouble finding the right medication. This article will highlight novelties in the field of diabetes during the year 2020.


Asunto(s)
Diabetes Mellitus Tipo 2 , Médicos Generales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Hipoglucemiantes/uso terapéutico , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
6.
Adv Exp Med Biol ; 1307: 213-230, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32006266

RESUMEN

In type 2 diabetes, the maladaptive upregulation of sodium-glucose cotransporter 2 (SGLT2) protein expression and activity contribute to the maintenance of hyperglycemia. By inhibiting these proteins, SGLT2 inhibitors increase urinary glucose excretion (UGE) that leads to fall in plasma glucose concentrations and improvement in all glycemic parameters. Clinical studies have demonstrated that in patients with type 2 diabetes, SGLT2 inhibitors resulted in sustained reductions in glycated hemoglobin (HbA1C), body weight, blood pressure and serum uric acid levels. Interestingly, the cardiovascular (CV) and renal outcome trials revealed the beneficial effects of SGLT2 inhibitors on CV and renal functions. Because the benefits were seen soon after initiation of SGLT2 inhibitors, these observations are explained by effects beyond their glucose lowering capacity. SGLT2 inhibitors also reduce liver fat in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. This chapter describes the basic information about SGLT2 inhibitors, current status of SGLT2 inhibitors in the management of type 2 diabetes and their beneficial effects in addition to glycemic control.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Ácido Úrico/sangre
7.
Adv Exp Med Biol ; 1307: 193-212, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32034729

RESUMEN

The risk of cardiovascular disease (CVD) (myocardial infarction, stroke, peripheral vascular disease) is twice in type 2 diabetes (T2D) patients compared to non-diabetic subjects. Furthermore, cardiovascular disease (CV) is the leading cause of death in patients with T2D.In the last years several clinical intervention studies with new anti-hyperglycaemic drugs have been published, and they have shown a positive effect on the reduction of mortality and cardiovascular risk in T2D patients. In particular, these studies evaluated sodium/glucose-2 cotransporter inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA).In secondary prevention, it was clearly demonstrated that SGLT2i and GLP-1RA drugs reduce CV events and mortality, and new guidelines consider now these drugs as first choice (after metformin) in the treatment of T2D; there are also some signs that they may be effective also in primary prevention of CVD. However, the mechanisms involved in cardiovascular protection are not yet fully understood, but they appear to be both "glycaemic" and "extra-glycaemic".In this review, we will examine the fundamental results of the clinical trials on SGLT2i and GLP-1RA, their clinical relevance in term of treatment of T2D, and we will discuss the mechanisms that may explain how these drugs exert their cardiovascular protective effects.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
8.
Adv Exp Med Biol ; 1307: 7-27, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32200500

RESUMEN

This chapter gives an overview of present knowledge and clinical aspects of antidiabetic drugs according to the recently available research evidence and clinical expertise.Many agents are acting on eight groups of pathophysiological mechanisms, which is commonly called as "Ominous Octet" by DeFronzo. The muscle, liver and ß-cell, the fat cell, gastrointestinal tract, α-cell, kidney, and brain play essential roles in the development of glucose intolerance in type 2 diabetic individuals (Defronzo, Diabetes 58:773-795, 2009).A treatment paradigm shift is seen in the initiation of anti-hyperglycemic agents from old friends (meglitinides or sulphonylürea) to newer agents effecting on GLP-1 RA or SGLT-2 inhibitors. It is mostly about the other protective positive effects of these agents for kidney, heart, etc. Although there are concerns for the long term safety profiles; they are used widely around the World. The delivery of patient-centered care, facilitating medication adherence, the importance of weight loss in obese patients, the importance of co-morbid conditions are the mainstays of selecting the optimal agent.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Comorbilidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Glucosa , Humanos , Cumplimiento de la Medicación , Atención Dirigida al Paciente , Pérdida de Peso
9.
Adv Exp Med Biol ; 1307: 85-114, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32488607

RESUMEN

Emergency admissions due to acute metabolic crisis in patients with diabetes remain some of the most common and challenging conditions. DKA (Diabetic Ketoacidosis), HHS (Hyperglycaemic Hyperosmolar State) and recently focused EDKA (Euglycaemic Diabetic Ketoacidosis) are life-threatening different entities. DKA and HHS have distinctly different pathophysiology but basic management protocols are the same. EDKA is just like DKA but without hyperglycaemia. T1D, particularly children are vulnerable to DKA and T2D, particularly elderly with comorbidities are vulnerable to HHS. But these are not always the rule, these acute conditions are often occur in different age groups with diabetes. It is essential to have a coordinated care from the multidisciplinary team to ensure the timely delivery of right treatment. DKA and HHS, in many instances can present as a mixed entity as well. Mortality rate is higher for HHS than DKA but incidences of DKA are much higher than HHS. The prevalence of HHS in children and young adults are increasing due to exponential growth of obesity and increasing T2D cases in this age group. Following introduction of SGLT2i (Sodium-GLucose co-Transporter-2 inhibitor) for T2D and off-label use in T1D, some incidences of EDKA has been reported. Healthcare professionals should be more vigilant during acute illness in diabetes patients on SGLT2i without hyperglycaemia to rule out EDKA. Middle aged, mildly obese and antibody negative patients who apparently resemble as T2D without any precipitating causes sometime end up with DKA which is classified as KPD (Ketosis-prone diabetes). Many cases can be prevented by following 'Sick day rules'. Better access to medical care, structured diabetes education to patients and caregivers are key measures to prevent acute metabolic crisis.


Asunto(s)
Cetoacidosis Diabética , Hiperglucemia , Anciano , Niño , Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/terapia , Urgencias Médicas , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Adulto Joven
10.
Adv Exp Med Biol ; 1307: 1-5, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32583142

RESUMEN

The number of people living with diabetes, the number of deaths attributable to it, and the cost of treating the disease and its complications are increasing exponentially. Centuries of research led to the discovery of insulin and other drugs based on pathophysiology from "the triumvirate to ominous octet". The agonists of the glucagon-like peptide-1 (GLP-1) receptor, and the inhibitors of the sodium-glucose transport protein 2 (SGLT2) are the new drugs that improve cardiovascular outcomes and provide renal protection, and they are being used increasingly for evidence-based treatment of type 2 diabetes. Bariatric surgery, when indicated, results in excellent weight- and metabolic-control, and in many instances even remission of diabetes. Technological advances like Flash glucose monitoring, continuous subcutaneous insulin infusion (CSII), and continuous glucose monitoring (CGM) have improved glycemic control, reduced episodes of severe hypoglycemia, and improved quality of life. For the treatment of diabetic macular edema intravitreal injection of several anti-VEGF agents are being used. Numerous people living in the middle- and low-income countries cannot afford the costs of care of diabetes. Institutions like the World Health Organization, the World Bank and the International Monetary Fund should roll out plans to convince the politicians to invest more in improving the diabetes care facilities.


Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Edema Macular , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Hemoglobina A Glucada , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Edema Macular/tratamiento farmacológico , Calidad de Vida , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
12.
Ann Pharmacother ; 55(1): 65-79, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32571083

RESUMEN

OBJECTIVE: To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH). DATA SOURCES: MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors. STUDY SELECTION AND DATA EXTRACTION: Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated. DATA SYNTHESIS: Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS. CONCLUSIONS: Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Hipoglucemiantes/administración & dosificación , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
14.
Lancet Diabetes Endocrinol ; 9(2): 106-116, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33357505

RESUMEN

BACKGROUND: SGLT2 inhibitors are a promising treatment option in patients with heart failure and reduced ejection fraction. We aimed to investigate the effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate (GFR) in patients with heart failure and reduced ejection fraction. METHODS: Empire HF Renal was a prespecified substudy of the investigator-initiated, double-blind, randomised, placebo-controlled Empire HF trial. The study was done at Herlev and Gentofte University Hospital (Herlev, Denmark), with patients recruited from four Danish heart failure outpatient clinics. Patients with New York Heart Association class I-III symptoms, with a left ventricular ejection fraction of 40% or lower, and on guideline-directed heart failure therapy were randomly assigned (1:1) to receive either oral empagliflozin 10 mg or matched placebo once daily for 12 weeks. The allocation sequence was computer-generated. Patients and study investigators were masked to treatment allocation. The coprimary prespecified renal outcomes were the between-group difference in the changes in estimated extracellular volume, estimated plasma volume, and measured GFR from baseline to 12 weeks. All analyses were done in the intention-to-treat population (apart from safety analyses, which were done in patients who received at least one dose of study drug), with no interim analyses done during the trial. The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585, and EudraCT, 2017-001341-27. FINDINGS: Between June 29, 2017, and July 15, 2019, we assessed 391 patients for eligibility, of whom 120 (31%) were randomly assigned to empagliflozin or placebo, including 105 (88%) without diabetes. In intention-to-treat analyses, 60 (100%) patients in the empagliflozin group and 59 (98%) patients in the placebo group were included for estimated extracellular volume and estimated plasma volume, and 59 (98%) patients in the empagliflozin group and 58 (97%) patients in the placebo group were included for measured GFR. Empagliflozin treatment resulted in reductions in estimated extracellular volume (adjusted mean difference -0·12 L, 95% CI -0·18 to -0·05; p=0·00056), estimated plasma volume (-7·3%, -10·3 to -4·3; p<0·0001), and measured GFR (-7·5 mL/min, -11·2 to -3·8; p=0·00010) compared with placebo. Five (8%) of 60 patients in the empagliflozin group and three (5%) of 60 patients in the placebo group had one or more serious adverse events. INTERPRETATION: In patients with heart failure and reduced ejection fraction, empagliflozin reduced estimated extracellular volume, estimated plasma volume, and measured GFR after 12 weeks. Fluid volume changes might be an important mechanism underlying the beneficial clinical effects of SGLT2 inhibitors. FUNDING: Research Council at Herlev and Gentofte University Hospital, Research and Innovation Foundation of the Department of Cardiology at Herlev and Gentofte University Hospital, Capital Region of Denmark, Danish Heart Foundation, and AP Møller Foundation for the Advancement of Medical Science.


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Glucósidos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Compuestos de Bencidrilo/administración & dosificación , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Glucósidos/administración & dosificación , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Volumen Plasmático/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacos
15.
Diab Vasc Dis Res ; 17(6): 1479164120971220, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33371732

RESUMEN

INTRODUCTION: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. MATERIALS AND METHODS: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)-dapagliflozin (n = 52) or empagliflozin (n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. RESULTS: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups (p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e' or left atrial volume index, decreased only in Group G at 36 months. CONCLUSIONS: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.


Asunto(s)
Albuminuria/tratamiento farmacológico , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Glucósidos/uso terapéutico , Incretinas/uso terapéutico , Riñón/efectos de los fármacos , Liraglutida/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Albuminuria/diagnóstico , Albuminuria/etiología , Albuminuria/fisiopatología , Compuestos de Bencidrilo/efectos adversos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Glucósidos/efectos adversos , Humanos , Incretinas/efectos adversos , Riñón/fisiopatología , Liraglutida/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Rigidez Vascular/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos
16.
Diab Vasc Dis Res ; 17(6): 1479164120975256, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33307785

RESUMEN

OBJECTIVE: It is well established that higher low-density lipoprotein (LDL)-cholesterol levels are associated with increased cardiovascular risk. We analyzed whether effects of empagliflozin on cardiovascular outcomes varied by different LDL-cholesterol levels at baseline in EMPA-REG OUTCOME. METHODS: Participants with type 2 diabetes and high cardiovascular risk received empagliflozin (10/25 mg) or placebo in addition to standard of care. We investigated the time to first 3P-MACE, cardiovascular death, hospitalization for heart failure (HHF) and all-cause mortality for empagliflozin versus placebo between baseline LDL-cholesterol categories <1.8, 1.8-<2.2, 2.2- <2.6, 2.6-3.0, and > 3.0 mmol/L, by a Cox regression including the interaction of baseline LDL-cholesterol category and treatment. RESULTS: Of the 7020 participants randomized and treated, 81.0% received lipid lowering therapy (77.0% statins). Mean ± SD LDL-cholesterol was 2.2 ± 0.9 mmol/L, and 38%/18%, had LDL-cholesterol <1.8/>3.0 mmol/L. Age, BMI, and HbA1c levels were balanced between the LDL-cholesterol subgroups, but those in the lowest versus highest group, had more coronary artery disease (83.0% vs 59.9%) and statin treatment (88.2% vs 50.9%). Empagliflozin consistently reduced all outcomes across LDL-cholesterol categories (all interaction p-values > 0.05). CONCLUSION: The beneficial cardiovascular effects of empagliflozin was consistent across higher and lower LDL-cholesterol levels at baseline.


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Glucósidos/efectos adversos , Humanos , Estudios Prospectivos , Medición de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
17.
BMC Med ; 18(1): 359, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-33190637

RESUMEN

BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.


Asunto(s)
Infecciones por Coronavirus/mortalidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/normas , Insulina/uso terapéutico , Metformina/uso terapéutico , Neumonía Viral/mortalidad , Respiración Artificial/estadística & datos numéricos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Anciano de 80 o más Años , Betacoronavirus , Estudios de Cohortes , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Diabetes Mellitus Tipo 2/complicaciones , Quimioterapia Combinada , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Hipoglucemiantes/uso terapéutico , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Modelos Logísticos , Masculino , Ventilación no Invasiva/estadística & datos numéricos , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Estudios Prospectivos , España
18.
Medicine (Baltimore) ; 99(41): e22660, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031329

RESUMEN

BACKGROUND: Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. This current research is a double blinded, randomized, and prospective trial to determine the effect of dapagliflozin on cardiovascular outcomes in type 2 diabetes. METHODS: This randomized controlled, double-blinded, single center trial is carried out according to the principles of Declaration of Helsinki. This present study was approved in institutional review committee of the Lianyungang Hospital affiliated to Xuzhou Medical University (LW-20200901001). All the patients received the informed consent. Diabetic patients were randomized equally to receive 28-week treatment with dapagliflozin or matching placebo. The major outcome of our current study was the change in the level of hemoglobin A1c (HbA1c) from the baseline to week 28. Secondary outcome measures contained the levels of fasting blood glucose, the mean change in seated systolic and diastolic blood pressure, body weight, and the mean change in calculated average daily insulin dose in patients treated with insulin at baseline, the other laboratory variables, and self-reported adverse events. The P < .05 was regarded as statistically significant. RESULTS: We assumed that the dapagliflozin administration in patients with type 2 diabetes would reduce HbA1c, body weight, systolic blood pressure, and achieve the goal of glycemic control, without adversely impacting cardiovascular risk. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5987).


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Método Doble Ciego , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Lancet Diabetes Endocrinol ; 8(11): 903-914, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33065060

RESUMEN

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors might enhance erythropoiesis and increase red blood cell mass. We assessed the long-term effects of canagliflozin on anaemia-related outcomes. METHODS: In a post-hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we included patients with type 2 diabetes and chronic kidney disease who were randomly assigned to treatment with canagliflozin or placebo at 690 sites in 34 countries. We assessed the effects of canagliflozin versus matched placebo on haemoglobin and haematocrit using linear mixed-effects models. The primary outcome of this post-hoc analysis was a composite outcome of investigator-reported anaemia or treatment for anaemia, which was assessed using Kaplan-Meier analysis and Cox regression models. All analyses were done by intention to treat. FINDINGS: Between March 24, 2014, and May 5, 2017, 4401 participants were randomly assigned to receive canagliflozin (100 mg; n=2202) or placebo (n=2199). At baseline, mean haemoglobin concentration was 132·0 g/L (SD 17·7), 1599 (36%) of 4401 participants had anaemia (defined as haemoglobin <130 g/L in men or <120 g/L in women), and 33 (<1%) of 4401 participants used erythropoiesis-stimulating agents. During a median follow-up period of 2·6 years (IQR 2·1-3·1), mean haemoglobin concentration was 7·1 g/L (95% CI 6·4-7·8) higher and haematocrit was 2·4% (2·2-2·6) higher in the canagliflozin group than the placebo group. Overall, 573 of 4401 participants had either an investigator-reported anaemia event or initiation of treatment for anaemia: 358 (8%) of 4401 participants reported anaemia events, 343 (8%) initiated iron preparations, 141 (3%) initiated erythropoiesis-stimulating agents, and 114 (2%) received blood transfusion. The risk of the composite outcome of anaemia events or initiation of treatment for anaemia was lower in the canagliflozin group than the placebo group (hazard ratio 0·65, 95% CI 0·55-0·77; p<0·0001). Compared with the placebo group, participants in the canagliflozin group also had lower risks of anaemia events alone (0·58, 0·47-0·72; p<0·0001), initiation of iron preparations (0·64, 0·52-0·80; p<0·0001), and need for erythropoiesis-stimulating agents (0·65, 0·46-0·91; p=0·012). INTERPRETATION: These data suggest that canagliflozin reduces the risk of anaemia-associated outcomes, including the need for erythropoiesis-stimulating agents, among patients with type 2 diabetes and chronic kidney disease. FUNDING: Janssen Research and Development.


Asunto(s)
Anemia/tratamiento farmacológico , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Anemia/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/epidemiología , Resultado del Tratamiento
20.
Nat Commun ; 11(1): 5162, 2020 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-33056984

RESUMEN

Bioactive natural C-glycosides are rare and chemical C-glycosylation faces challenges while enzymatic C-glycosylation catalyzed by C-glycosyltransferases provides an alternative way. However, only a small number of C-glycosyltransferases have been found, and most of the discovered C-glycosyltransferases prefer to glycosylate phenols with an acyl side chain. Here, a promiscuous C-glycosyltransferase, AbCGT, which is capable of C-glycosylating scaffolds lacking acyl groups, is identified from Aloe barbadensis. Based on the substrate promiscuity of AbCGT, 16 C-glycosides with inhibitory activity against sodium-dependent glucose transporters 2 are chemo-enzymatically synthesized. The C-glycoside 46a shows hypoglycemic activity in diabetic mice and is biosynthesized with a cumulative yield on the 3.95 g L‒1 scale. In addition, the key residues involved in the catalytic selectivity of AbCGT are explored. These findings suggest that AbCGT is a powerful tool in the synthesis of lead compounds for drug discovery and an example for engineering the catalytic selectivity of C-glycosyltransferases.


Asunto(s)
Aloe/enzimología , Glicósidos/biosíntesis , Glicosiltransferasas/metabolismo , Proteínas de Plantas/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/metabolismo , Aloxano/toxicidad , Aloe/genética , Animales , Biocatálisis , Glucemia/análisis , Glucemia/efectos de los fármacos , Clonación Molecular , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Descubrimiento de Drogas/métodos , Femenino , Glicósidos/farmacología , Glicósidos/uso terapéutico , Glicosilación , Glicosiltransferasas/genética , Glicosiltransferasas/aislamiento & purificación , Humanos , Masculino , Ratones , Proteínas de Plantas/genética , Proteínas de Plantas/aislamiento & purificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Transportador 2 de Sodio-Glucosa/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Especificidad por Sustrato
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