RESUMEN
Background: Antidiabetic drugs are widely used in clinical practice as essential drugs for the treatment of diabetes. The effect of hypoglycemic drugs on erectile dysfunction has not been fully proven due to the presence of multiple confounding factors. Methods: Two-sample Mendelian randomization (TSMR) was used to examine the causal effect of antidiabetic drugs (including metformin, insulin and gliclazide) on erectile dysfunction. We used five robust analytic methods, of which the inverse variance weighting (IVW) method was the primary method, and also assessed factors such as sensitivity, pleiotropy, and heterogeneity. Effect statistics for exposures and outcomes were downloaded from publicly available data sets, including open Genome-Wide Association Studies (GWAS) and the UK Biobank (UKB). Results: In some of the hypoglycemic drug use, there was a significant causal relationship between metformin use and erectile dysfunction [Beta: 4.9386; OR:1.396E+02 (95% CI:9.13-2135); p-value: 0.0004), suggesting that metformin increased the risk of erectile dysfunction development. Also, we saw that gliclazide use also increased the risk of erectile dysfunction [Beta: 11.7187; OR:0.0125 (95% CI:12.44-1.21E+09); P value: 0.0125). There was no significant causal relationship between insulin use and erectile dysfunction [Beta: 3.0730; OR:21.6071 (95% CI:0.24-1942.38); p-value: 0.1806).Leave-one-out, MR-Egger, and MR-PRESSO analyses produced consistent results. Conclusion: The use of metformin and gliclazide have the potential to increase the risk of erectile dysfunction. There is no causal relationship between the use of insulin and erectile dysfunction.
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Disfunción Eréctil , Hipoglucemiantes , Análisis de la Aleatorización Mendeliana , Metformina , Humanos , Masculino , Disfunción Eréctil/inducido químicamente , Disfunción Eréctil/epidemiología , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Metformina/uso terapéutico , Estudio de Asociación del Genoma Completo , Insulina/efectos adversos , Gliclazida/efectos adversos , Gliclazida/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genéticaRESUMEN
BACKGROUND: With the increasing prevalence of obesity and type 2 diabetes, the availability of different treatment options remains essential. Studies comparing the outcomes of glucagon-like peptide 1 receptor agonists with those of metabolic bariatric surgery in patients with type 2 diabetes and obesity are lacking. METHODS: Using propensity score matching, based on data from several nationwide clinical registries, patients who underwent primary metabolic bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) were matched with patients who received glucagon-like peptide 1 receptor agonists. Outcome measures included the occurrence of major cardiovascular events, microvascular complications, and potential side effects (alcohol/substance abuse, self-harm, and fractures). RESULTS: Over a mean follow-up of 7 years, major cardiovascular events occurred in 191 of 2039 patients (cumulative incidence 14.5%) in the surgery group compared with 247 of 2039 patients (19.6%) in the glucagon-like peptide 1 receptor agonist group (HR 0.75 (95% c.i. 0.62 to 0.91), P = 0.003). Patients in the surgery group had lower haemoglobin A1c values 5 years after treatment (mean difference 9.82 (95% c.i. 8.51 to 11.14)â mmol/mol, P < 0.001) and fewer microvascular complications (retinopathy HR 0.88 (95% c.i. 0.79 to 0.99), P = 0.039; nephropathy HR 0.72 (95% c.i. 0.66 to 0.80), P < 0.001; and neuropathy or leg ulcers HR 0.82 (95% c.i. 0.74 to 0.92), P < 0.001), but a higher risk of alcohol/substance abuse (HR 2.56 (95% c.i. 1.87 to 3.50), P < 0.001), self-harm (HR 1.41 (95% c.i. 1.17 to 1.71), P < 0.001), and fractures (HR 1.86 (95% c.i. 1.11 to 3.12), P = 0.019). CONCLUSION: Compared with glucagon-like peptide 1 receptor agonist treatment, metabolic bariatric surgery is associated with superior metabolic outcomes and a lower risk of major cardiovascular events in patients with type 2 diabetes and obesity, but a higher risk of alcohol/substance abuse, self-harm, and fractures.
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Cirugía Bariátrica , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Agonistas Receptor de Péptidos Similares al Glucagón , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cirugía Bariátrica/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Puntaje de Propensión , Resultado del Tratamiento , Agonistas Receptor de Péptidos Similares al Glucagón/efectos adversos , Agonistas Receptor de Péptidos Similares al Glucagón/uso terapéuticoRESUMEN
SGLT2 inhibitors (gliflozins) have proven their efficacy in reducing complications due to atherosclerotic cardiovascular disease, heart failure and chronic kidney disease both in placebo-controlled clinical trials and in real-life studies versus other glucose-lowering agents (except GLP-1 analogues) in patients with type 2 diabetes. Hence, observational studies demonstrate that they are poorly used in -clinical practice, including in patients at high cardiorenal risk. -Reasons are multiple and involve physicians, patients and health care system with restricted criteria for prescription and reimbursement in many countries. Bridging the gap between scientific proves from evidence-based medicine and clinical practice represents a major health-care issue.
Les inhibiteurs des SGLT2 (gliflozines) ont prouvé leur efficacité pour réduire le risque des complications de la maladie athéromateuse, de l'insuffisance cardiaque et de la maladie rénale chronique dans des essais cliniques contrôlés versus placebo et dans des études de vraie vie versus les autres antidiabétiques (sauf les analogues du GLP-1) chez des patients avec un diabète de type 2. Pourtant, les études observationnelles démontrent qu'ils sont peu utilisés en pratique clinique, y compris chez des patients à haut risque cardiorénal. Les raisons en sont multiples et impliquent le médecin prescripteur, le patient et, éventuellement, le système de soins avec des critères d'utilisation ou de remboursement restreints. Combler le fossé entre l'évidence scientifique apportée par la médecine factuelle et la pratique clinique représente un enjeu majeur de santé publique.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Enfermedades Cardiovasculares/prevención & control , Insuficiencia Cardíaca/tratamiento farmacológico , Medicina Basada en la EvidenciaAsunto(s)
United States Food and Drug Administration , Humanos , Estados Unidos/epidemiología , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/administración & dosificación , Péptido 1 Similar al Glucagón/agonistas , Péptido 1 Similar al Glucagón/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Anciano , Liraglutida/efectos adversos , Liraglutida/uso terapéutico , Exenatida/efectos adversos , Exenatida/administración & dosificación , Adulto , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/epidemiologíaAsunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Linagliptina , Penfigoide Ampolloso , Humanos , Linagliptina/efectos adversos , Linagliptina/uso terapéutico , Penfigoide Ampolloso/mortalidad , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Anciano , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Anciano de 80 o más Años , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Factores de Riesgo , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Metformin-associated lactic acidosis (MALA) is a rare and potentially life-threatening complication of metformin use. It typically occurs in patients who are diabetic and also have other risk factors for lactic acidosis, including kidney and liver conditions, malignancy, or use of certain medications. We report a case of MALA in a man in his 70s with diabetes who presented with gradually worsening gastrointestinal symptoms, including severe abdominal pain and nausea. He reported these symptoms in the setting of metformin use with an acute kidney injury (AKI), likely brought on by poor oral intake and excessive antibiotic use for a urinary tract infection. He was promptly started on intravenous fluids with a bicarbonate drip to concurrently treat his prerenal AKI and lactic acidosis, which resulted in rapid resolution of his symptoms. Renal function normalised within 12 days of admission. Since diabetic patients commonly use metformin and are also at higher risk of renal dysfunction, this case highlights the vulnerability of this group of patients and the need for increased knowledge and awareness of MALA.
Asunto(s)
Acidosis Láctica , Lesión Renal Aguda , Hipoglucemiantes , Metformina , Humanos , Metformina/efectos adversos , Acidosis Láctica/inducido químicamente , Masculino , Hipoglucemiantes/efectos adversos , Anciano , Lesión Renal Aguda/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Dolor Abdominal/inducido químicamenteRESUMEN
BACKGROUND: Postoperative cognitive impairment are common neural complications in older surgical patients and exacerbate the burden of medical care on families and society. METHODS: A total of 140 older patients who were scheduled for elective orthopaedic surgery or pancreatic surgery with general anaesthesia were randomly assigned to Group S or Group I with a 1:1 allocation. Patients in Group S and Group I received intranasal administration of 400 µL of normal saline or 40 IU/400 µL of insulin, respectively, once daily from 5 minutes before anaesthesia induction until 3 days postoperatively. Perioperative cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MoCA-B) at 1 day before and 3 days after surgery and postoperative delirium (POD) incidence was assessed using the 3-minute Diagnostic Interview for CAM (3D-CAM) on postoperative days 1-3. Serum levels of interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), S100-ß and C-reactive protein (CRP) were measured on the first day after surgery. RESULTS: Insulin treatment significantly increased postoperative MMSE and MoCA-B scores in group I than in group S (P < 0.001, P = 0.001, respectively), decreased the incidence of POD within the 3-day postoperative period in Group I than in Group S (10.9% vs 26.6%, P = 0.024), and inhibited postoperative IL-6 and S100-ß levels in Group I compared to Group S (P = 0.034, P = 0.044, respectively). CONCLUSIONS: Intranasal insulin administration is thus suggested as a potential therapy to improve postoperative cognition in older patients undergoing surgery. However, a more standardized multi-centre, large-sample study is needed to further validate these results.
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Administración Intranasal , Cognición , Insulina , Complicaciones Cognitivas Postoperatorias , Humanos , Masculino , Femenino , Anciano , Método Doble Ciego , Insulina/administración & dosificación , Cognición/efectos de los fármacos , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/diagnóstico , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Anciano de 80 o más Años , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Pruebas de Estado Mental y Demencia , Resultado del Tratamiento , Biomarcadores/sangre , Procedimientos Ortopédicos/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: The prevalence of type 2 diabetes (DM) has been increasing globally, particularly among older adults who are more susceptible to DM-related complications. Elderly individuals with diabetes are at higher risk of developing hypoglycemia compared with younger diabetes patients. Hypoglycemia in elderly patients can result in serious consequences such as cognitive changes, increased risk of falls, heart and other vascular problems, and even high mortality rate. OBJECTIVE: To assess prevalence, and factors associated with hypoglycemia events among geriatric outpatients with type 2 diabetes mellitus. METHODS: The study was conducted at King Abdullah University Hospital (KAUH) at the outpatient diabetes clinic from October 1st, 2022 to August 1st, 2023. Variables such as socio-demographics, medication history, and comorbidities were obtained using electronic medical records. The prevalence of hypoglycemia was determined through patient interviews during their clinic visit. Patients were prospectively monitored for hospital admissions, emergency department visits, and mortality using electronic medical records over a three-month follow-up period. Logistic regression models were conducted to identify factors associated with hypoglycemia and hospital admissions/ emergency visits. Ethical Approval (Reference # 53/151/2022) was obtained on 19/9/2022. RESULTS: Electronic medical charts of 640 patients who have type 2 diabetes mellitus and age ≥ 60 years were evaluated. The mean age ± SD was 67.19 (± 5.69) years. Hypoglycemia incidents with different severity levels were prevalent in 21.7% (n = 139) of the patients. Insulin administration was significantly associated with more hypoglycemic events compared to other antidiabetic medication. Patients with liver diseases had a significantly higher risk of hypoglycemia, with odds 7.43 times higher than patients without liver diseases. Patients with dyslipidemia also had a higher risk of hypoglycemia (odd ratio = 1.87). Regression analysis revealed that hypoglycemia and educational level were significant predictors for hospital admission and emergency department (ER) visits. Hypoglycemia was a positive predictor, meaning it increased the odds of these outcomes, while having a college degree or higher was associated with reduced odds of hospital admission and ER visits. CONCLUSION: Current study identified a considerable prevalence of hypoglycemia among older patients with type 2 diabetes, particularly, among those with concurrent liver diseases and dyslipidemia. Furthermore, hypoglycemia was associated with an increased rate of emergency department visits and hospital admissions by 2 folds in this population.
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Diabetes Mellitus Tipo 2 , Hipoglucemia , Pacientes Ambulatorios , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemia/epidemiología , Anciano , Masculino , Femenino , Prevalencia , Pacientes Ambulatorios/estadística & datos numéricos , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Hospitalización/estadística & datos numéricosRESUMEN
BACKGROUND: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. METHODS: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. FINDINGS: Between Oct 31, 2018, and March 31, 2021, 17â604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17â604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. INTERPRETATION: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. FUNDING: Novo Nordisk.
Asunto(s)
Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Obesidad , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Método Doble Ciego , Anciano , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Inyecciones SubcutáneasRESUMEN
Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been reported to increase the risk of acute pancreatitis (AP). This real-world study did not observe a higher frequency of AP with GLP-1RA exposure in adults with T2D and a prior history of AP regardless of etiology.
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Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Pancreatitis , Humanos , Pancreatitis/epidemiología , Pancreatitis/inducido químicamente , Receptor del Péptido 1 Similar al Glucagón/agonistas , Masculino , Femenino , Persona de Mediana Edad , Incidencia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Anciano , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Enfermedad Aguda , AdultoRESUMEN
BACKGROUND: Western guidelines often recommend biguanides as the first-line treatment for diabetes. However, dipeptidyl peptidase-4 (DPP-4) inhibitors, alongside biguanides, are increasingly used as the first-line therapy for type 2 diabetes (T2DM) in Japan. However, there have been few studies comparing the effectiveness of biguanides and DPP-4 inhibitors with respect to diabetes-related complications and cardio-cerebrovascular events over the long term, as well as the costs associated. OBJECTIVE: We aimed to compare the outcomes of patients with T2DM who initiate treatment with a biguanide versus a DPP-4 inhibitor and the long-term costs associated. METHODS: We performed a cohort study between 2012 and 2021 using a new-user design and the Shizuoka Kokuho database. Patients were included if they were diagnosed with T2DM. The primary outcome was the incidence of cardio-cerebrovascular events or mortality from the initial month of treatment; and the secondary outcomes were the incidences of related complications (nephropathy, renal failure, retinopathy, and peripheral neuropathy) and the daily cost of the drugs used. Individuals who had experienced prior events during the preceding year were excluded, and events within 6 months of the start of the study period were censored. Propensity score matching was performed to compare between two groups. RESULTS: The matched 1:5 cohort comprised 529 and 2,116 patients who were initially treated with a biguanide or a DPP-4 inhibitor, respectively. Although there were no significant differences in the incidence of cardio-cerebrovascular events or mortality and T2DM-related complications between the two groups (p = 0.139 and p = 0.595), daily biguanide administration was significantly cheaper (mean daily cost for biguanides, 61.1 JPY; for DPP-4 inhibitors, 122.7 JPY; p<0.001). CONCLUSION: In patients with T2DM who initiate pharmacotherapy, there were no differences in the long-term incidences of cardio-cerebrovascular events or complications associated with biguanide or DPP-4 use, but the former was less costly.
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Biguanidas , Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Inhibidores de la Dipeptidil-Peptidasa IV , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biguanidas/efectos adversos , Biguanidas/economía , Biguanidas/uso terapéutico , Enfermedades Cardiovasculares/economía , Enfermedades Cardiovasculares/tratamiento farmacológico , Estudios de Cohortes , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/economía , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/economía , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/economía , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/economía , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/economía , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Hipoglucemiantes/economía , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Japón , Resultado del TratamientoRESUMEN
INTRODUCTION: From 2008 and following the withdrawal of rosiglitazone, obligatory cardiovascular outcomes trials are performed for glucose lowering drugs introduced to the market to ensure their cardiovascular (CV) safety. Paradoxically, these studies have demonstrated CV safety but also shown additional cardio-reno-vascular protection of some therapeutic agents. Additionally, nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) have emerged as novel drugs for cardio - and renoprotection in type 2 diabetes (T2D) and chronic kidney disease (CKD). In addition to atherosclerotic CV disease, heart failure (HF) and CKD are important clinical problems in T2D leading to poor quality of life and premature death as such cardio-reno-vascular protection is an important clinical issue. AREAS COVERED: We provide new insights into pharmacotherapeutic cardio-reno-vascular protection in T2D based on the new glucose lowering drugs and ns-MRA. PUB MED/CINAHL/Web of Science/Scopus were searched (May 2024). EXPERT OPINION: The conventional glucose lowering approach alone which was implemented for decades is now replaced by the use of disease modifying drugs which lower the rates of CV events, HF decompensation, hospitalization due to HF, slow progression of CKD and all-cause mortality. Indeed, the choice of medications in T2D should be focused on underlying co-morbidities with cardio-reno-vascular protection rather than a gluco-centric approach.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Calidad de Vida , AnimalesRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is increasingly being diagnosed in older adults. Our objective is to assess the advantages and potential drawbacks of different glucose-lowering medications in this specific population. METHODS: A network meta-analysis was conducted to identify randomized controlled trials that examined patient-centered outcomes in adults aged ≥65 years with T2DM. We searched PubMed, Cochrane CENTRAL, and Embase up to September 23, 2023. Quality of eligible studies were assessed using the Cochrane RoB 2.0 tool. RESULTS: A total of 22 trials that involved 41 654 participants were included, incorporating sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, sulfonylureas (SU) and acarbose. Our findings reveal that GLP-1RAs reduce the risk of major adverse cardiovascular events (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.71 to 0.97) and body weight (mean difference [MD], -3.87 kg; 95% CI, -5.54 to -2.21). SGLT2 inhibitors prevent hospitalization for heart failure (RR, 0.66; 95% CI, 0.57 to 0.77), renal composite outcome (RR, 0.69; 95% CI, 0.53 to 0.89), and reduce body weights (MD, -1.85 kg; 95% CI, -2.42 to -1.27). SU treatment increases the risk of any hypoglycaemia (RR, 4.19; 95% CI, 3.52 to 4.99) and severe hypoglycaemia (RR, 7.06; 95% CI, 3.03 to 16.43). GLP-1RAs, SGLT2 inhibitors, metformin, SU and DPP-4 inhibitors are effective in reducing glycaemic parameters. Notably, the number of treatments needed decreases in most cases as age increases. CONCLUSIONS: Novel glucose-lowering medications with benefits that outweigh risks should be prioritized for older patients with diabetes.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Anciano , Femenino , Humanos , Masculino , Factores de Edad , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Resultado del TratamientoAsunto(s)
Acidosis Láctica , Síndrome Coronario Agudo , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Hipoglucemiantes , Insulina , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Metformina/efectos adversos , Síndrome Coronario Agudo/mortalidad , Acidosis Láctica/inducido químicamente , Acidosis Láctica/mortalidad , Acidosis Láctica/sangre , Femenino , Masculino , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Insulina/efectos adversos , Anciano , Hospitalización , Persona de Mediana EdadRESUMEN
INTRODUCTION: Gliptins are a relatively recent class of oral antidiabetic agents used in the treatment of type 2 diabetes. The aim of this study is to identify the adverse effects of gliptins in patients with type 2 diabetes, compare the tolerability of these drugs with data from the literature, and determine patients' behavior in the face of these adverse effects with a view to optimizing their management. METHODS: Our study is cross-sectional, descriptive, and analytical, involving 100 patients aged over 20 years, followed at the Endocrinology Department of the Military Hospital Mohammed V. RESULTS: The average age of the patients was 63 years, with a sex ratio F/H of 1.13. The median age of diabetes in the patients was 13 years, with an average blood glucose level of 1.64 and an average hemoglobin A1c of 8.26. The comorbidities were 30% cardiovascular disease, 25% hypertension, and 14% dyslipidemia, and 30% of patients had no comorbidities. Forth-six percent of patients reported adverse events and 54% did not report any adverse event. Twenty-eight percent of the adverse events were gastrointestinal, 18% skin disorders, 14% urinary tract infections, 12% hypoglycemia, 12% nervous system disorders, 8% airway infections, and 8% general disorders. CONCLUSION: This study shows that gliptins remain a safe option as the side effects seem fairly well tolerated by patients. Adverse events may impact patient compliance and pose a problem of adherence to treatment. Thus, it would be advantageous to develop therapeutic education for diabetic patients to detect and manage adverse effects.
Résumé Introduction:Les gliptines sont une classe relativement récente d'antidiabétiques oraux utilisés dans le traitement du diabète de type 2. Le but de cette étude est d'identifier les effets indésirables des gliptines chez les patients diabétiques de type 2, de comparer la tolérance de ces médicaments avec les données de la littérature et de déterminer le comportement des patients face à ces effets indésirables afin d'optimiser leur prise en charge.Méthodes:Notre étude est transversale, descriptive et analytique, portant sur 100 patients âgés de plus de 20 ans, suivis au service d'endocrinologie de l'hôpital militaire Mohammed V.Résultats:L'âge moyen des patients était de 63 ans, avec un sex-ratio F/H de 1,13. L'âge médian d'apparition du diabète chez les patients était de 13 ans, avec une glycémie moyenne de 1,64 et une hémoglobine A1c moyenne de 8,26%. Les comorbidités étaient les suivantes: 30 % de maladies cardiovasculaires, 25 % d'hypertension et 14 % de dyslipidémie; 30 % des patients n'avaient aucune comorbidité. Quarante-six pour cent des patients ont signalé des effets indésirables et 54 % n'ont signalé aucun effet indésirable. Vingt-huit pour cent des effets indésirables étaient d'ordre gastro-intestinal, 18 % des troubles cutanés, 14 % des infections urinaires, 12 % des hypoglycémies, 12 % des troubles du système nerveux, 8 % des infections des voies respiratoires et 8 % des troubles généraux.Conclusion:Cette étude montre que les gliptines restent une option sûre car les effets secondaires semblent assez bien tolérés par les patients. Les effets indésirables peuvent avoir un impact sur la compliance des patients et poser un problème d'adhésion au traitement. Ainsi, il serait avantageux de développer l'éducation thérapeutique des patients diabétiques pour détecter et gérer les effets indésirables.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Marruecos/epidemiología , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Anciano , Adulto , Glucemia/efectos de los fármacos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inducido químicamente , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipertensión/epidemiologíaAsunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversosRESUMEN
BACKGROUND: Diabetic Mellitus (DM) has progressively emerged as a worldwide health problem, leading to the widespread deployment of antidiabetic drugs as the primary therapy in the global population. The incidence of diabetes medications-related movement disorders (drMD) is noteworthy but underestimated by clinical practitioners. RESEARCH DESIGN AND METHODS: In order to address the incidence of drMD in DM patients and realize the serious outcomes associated with drMD, we conducted a real-world pharmacovigilance study of 612,043 DM patients using the FDA Adverse Event Reporting System (FAERS) database from January 2004 to September 2023. Reporting Odd Ratio (ROR) was calculated to reflect the risk of drMD. A multivariable logistic regression analysis was employed to adjust crude ROR with the mixed factors including age, sex and various antidiabetic treatments. Afterward, a Mendelian Randomization (MR) study was performed to elucidate the underlying genetic correlation between the genetically proxied targets of antidiabetic drugs and motor disorders. RESULTS: Among 11,729 cases of motor adverse events in DM patients, six categories of drMD were significantly associated with DM medications. Noticeably, metformin was revealed to drastically increase the incidence of parkinsonism (adjusted ROR:3.97; 95 %CI (3.03, 5.19), p = 5.68e-24), bradykinesia (adjusted ROR:1.69; 95 %CI (1.07,2.59), p = 0.02) and irregular hyperkinesia, including chorea, choreoathetosis and athetosis. Insulin/insulin analogues and GLP-1 analogues presented notably higher odds of tremor: the adjusted ROR (aROR) of insulin and GLP-1 analogue is respectively 1.24 (95 %CI (1.15,1.34), p = 2.51e-08) and 1.78 (95 %CI (1.65,1.91), p = 5.64e-54). The combined therapeutic effects of multiple genetic variants of metformin, especially AMP-activated protein kinase (AMPK) were markedly linked to a greater likelihood of developing secondary parkinsonism (OR:10.816, p = 0.049) according to MR analyses. CONCLUSION: The use of antidiabetic medications was significantly related to an increased incidence of movement disorders in DM patients. Moreover, MR analyses provided further genetic evidence for the pharmacovigilance study. This comprehensive investigation might help physicians recognize neurological adverse events associated with antidiabetic treatments and administer effective interventions.