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1.
BMJ Case Rep ; 15(9)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36113958

RESUMO

Euglycaemic diabetic ketoacidosis is a serious but rare adverse effect of treatment with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A man in his 60s with type 2 diabetes mellitus underwent total hip replacement for an intracapsular neck of femur fracture. His SGLT-2 inhibitor was continued perioperatively and blood glucose levels were normal throughout the admission. A diagnosis of severe euglycaemic diabetic ketoacidosis was made in the operating theatre which required treatment in a critical care unit. This resulted in increased morbidity due to decreased postoperative mobilisation and a new requirement for subcutaneous insulin. This case highlights the need for withholding SGLT-2 inhibitors in patients admitted for emergency surgery and a need for regular ketone monitoring in these patients, even in the context of normoglycaemia.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Ortopedia , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/diagnóstico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Cetonas/efeitos adversos , Masculino , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
2.
Front Public Health ; 10: 990281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091534

RESUMO

Objective: Regarding the effects and practical application of insulin pumps on patients with type 1 diabetes mellitus (T1DM), the real-world evidence is limited especially concerning the incidence of hypoglycemia. This study aimed to compare the efficacy of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy on glycemic metrics evaluated by retrospective continuous glucose monitoring (CGM) in Chinese patients with T1DM. Methods: In total, 362 T1DM Chinese patients from the outpatient department of the Second Xiangya Hospital, Central South University, who underwent intensive insulin therapy and used a retrospective CGM system were included in this retrospective cross-sectional study. Comprehensive analysis of clinical and biological features and retrospective CGM derived-metrics was performed on the 362 enrolled T1DM patients who underwent CSII (n = 61) or MDI (n = 301) therapy (defined as 4 or more insulin injections per day). Results: Our findings demonstrated that patients who underwent CSII therapy, compared with those who received MDI therapy, had lower levels of hemoglobin A1c (HbA1c) and fasting blood glucose; moreover, CSII therapy was associated with better glycemic outcomes in terms of increasing time in range (TIR), decreasing time above range (TAR), and achieving CGM-associated targets of TIR ≥70% and TAR <25%. However, patients who underwent CSII therapy did not experience decreasing time below range (TBR), achieving CGM-associated targets of TBR <4%, and reduction of the risk of hypoglycemia as evidenced by comparing TBR and low blood glucose index (LBGI) between the two treatment regimens. The parameters of glycemic variability, such as standard deviation of glucose (SD), mean amplitude glycemic excursion (MAGE), and large amplitude glycemic excursion (LAGE) in T1DM patients who underwent CSII therapy outperformed. Conclusion: Our results provided further evidence that CSII therapy is safe and effective for management of Chinese T1DM patients, which was confirmed by a lower HbA1c level and better CGM-derived metrics but no demonstration of improvment in the risk of hypoglycemia. To achieve more satisfactory glycemic outcomes through the utilization of CSII therapy for Chinese T1DM patients, a strong physician-patient relationship is essential.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Glicemia/análise , Automonitorização da Glicemia/efeitos adversos , Estudos Transversais , Análise de Dados , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose/uso terapêutico , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/uso terapêutico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/efeitos adversos , Insulina/uso terapêutico , Sistemas de Infusão de Insulina/efeitos adversos , Estudos Retrospectivos
3.
Artigo em Inglês | MEDLINE | ID: mdl-36109050

RESUMO

INTRODUCTION: Type 2 diabetes is a risk factor for dementia and Parkinson's disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subtypes and PD compared with sulfonylureas. RESEARCH DESIGN AND METHODS: A new user comparator study design was conducted in patients ≥50 years old with diabetes who were new users of metformin or sulfonylureas between 2006 and 2018. Primary outcomes were all-cause dementia and PD. Secondary outcomes were Alzheimer's disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI). Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the HRs. Subanalyses included stratification by age, race, renal function, and glycemic control. RESULTS: We identified 96 140 and 16 451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4±8.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3207 patients developed all-cause dementia (2256 (2.3%) metformin, 951 (5.8%) sulfonylurea users) and 760 patients developed PD (625 (0.7%) metformin, 135 (0.8%) sulfonylurea users). After IPTW, HRs for all-cause dementia and PD were 0.80 (95% CI 0.73 to 0.88) and 1.00 (95% CI 0.79 to 1.28). HRs for AD, VD and MCI were 0.81 (0.70-0.94), 0.79 (0.63-1.00) and 0.91 (0.79-1.04). Stronger associations were observed in patients who were younger (<75 years old), Caucasian, and with moderate renal function. CONCLUSIONS: Metformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI. Age and renal function modified risk reduction. Our findings support the hypothesis that metformin provides more neuroprotection for dementia than sulfonylureas but not for PD, but further work is required to assess causality.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Metformina , Doença de Parkinson , Idoso , Demência/epidemiologia , Demência/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Compostos de Sulfonilureia/efeitos adversos
4.
JAMA ; 328(10): 968-979, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098720

RESUMO

Importance: Of youths diagnosed with type 2 diabetes, many develop microvascular complications by young adulthood. Objective: To review the evidence on benefits and harms of screening children and adolescents for prediabetes and type 2 diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through May 3, 2021; references; experts; literature surveillance through July 22, 2022. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or type 2 diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: This review included 8 publications (856 participants; mean age, 14 years [range, 10-17 years]). Of those, 6 were from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. No eligible studies directly evaluated the benefits or harms of screening. One randomized clinical trial (RCT) (TODAY; n = 699 adolescents with obesity; mean age, 14 years) comparing metformin, metformin plus rosiglitazone, and metformin plus lifestyle intervention reported that 2 youths with recently diagnosed diabetes developed kidney impairment (0 vs 1 vs 1, respectively; P > .99) and 11 developed diabetic ketoacidosis (5 vs 3 vs 3, respectively; P = .70). One RCT of 75 adolescents (mean age, 13 years) with obesity with prediabetes compared an intensive lifestyle intervention with standard care and reported that no participants in either group developed diabetes, although follow-up was only 6 months. Regarding harms of interventions, 2 RCTs assessing different comparisons enrolled youths with recently diagnosed diabetes. Major hypoglycemic events were reported by less than 1% of participants. Minor hypoglycemic events were more common among youths treated with metformin plus rosiglitazone than among those treated with metformin or metformin plus lifestyle intervention in TODAY (8.2% vs 4.3% vs 3.4%, P = .05). In 1 study, gastrointestinal adverse events were more commonly reported by those taking metformin than by those taking placebo (abdominal pain: 25% vs 12%; nausea/vomiting: 17% vs 10%; P not reported). Conclusions and Relevance: No eligible studies directly evaluated the benefits or harms of screening for prediabetes and type 2 diabetes in children and adolescents. For youths with prediabetes or recently diagnosed (not screen-detected) diabetes, the only eligible trials reported few health outcomes and found no difference between groups, although evidence was limited by substantial imprecision and a duration of follow-up likely insufficient to assess health outcomes.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Programas de Rastreamento , Metformina , Estado Pré-Diabético , Adolescente , Comitês Consultivos , Criança , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêutico , Obesidade/complicações , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/tratamento farmacológico , Serviços Preventivos de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Rosiglitazona/efeitos adversos , Rosiglitazona/uso terapêutico
5.
N Engl J Med ; 387(12): 1063-1074, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36129996

RESUMO

BACKGROUND: The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain. METHODS: In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, measured quarterly, of 7.0% or higher that was subsequently confirmed, and the secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%. RESULTS: A total of 5047 participants (19.8% Black and 18.6% Hispanic or Latinx) who had received metformin for type 2 diabetes were followed for a mean of 5.0 years. The cumulative incidence of a glycated hemoglobin level of 7.0% or higher (the primary metabolic outcome) differed significantly among the four groups (P<0.001 for a global test of differences across groups); the rates with glargine (26.5 per 100 participant-years) and liraglutide (26.1) were similar and lower than those with glimepiride (30.4) and sitagliptin (38.1). The differences among the groups with respect to a glycated hemoglobin level greater than 7.5% (the secondary outcome) paralleled those of the primary outcome. There were no material differences with respect to the primary outcome across prespecified subgroups defined according to sex, age, or race or ethnic group; however, among participants with higher baseline glycated hemoglobin levels there appeared to be an even greater benefit with glargine, liraglutide, and glimepiride than with sitagliptin. Severe hypoglycemia was rare but significantly more frequent with glimepiride (in 2.2% of the participants) than with glargine (1.3%), liraglutide (1.0%), or sitagliptin (0.7%). Participants who received liraglutide reported more frequent gastrointestinal side effects and lost more weight than those in the other treatment groups. CONCLUSIONS: All four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, more effective in achieving and maintaining target glycated hemoglobin levels. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Liraglutida/efeitos adversos , Metformina/efeitos adversos , Fosfato de Sitagliptina/efeitos adversos , Compostos de Sulfonilureia , Resultado do Tratamento
7.
N Engl J Med ; 387(12): 1075-1088, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36129997

RESUMO

BACKGROUND: Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes. METHODS: We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes. The randomly assigned therapies were insulin glargine U-100 (hereafter, glargine), glimepiride, liraglutide, and sitagliptin. Prespecified secondary outcomes with respect to microvascular and cardiovascular disease included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2 of body-surface area, diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, cardiovascular events (major adverse cardiovascular events [MACE], hospitalization for heart failure, or an aggregate outcome of any cardiovascular event), and death. Hazard ratios are presented with 95% confidence limits that are not adjusted for multiple comparisons. RESULTS: During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group. CONCLUSIONS: In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Insuficiência Cardíaca , Hipertensão , Metformina , Albuminúria/complicações , Glicemia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neuropatias Diabéticas/induzido quimicamente , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/tratamento farmacológico , Hemoglobina A Glicada , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/complicações , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Liraglutida/uso terapêutico , Metformina/uso terapêutico , Fosfato de Sitagliptina/efeitos adversos , Compostos de Sulfonilureia
8.
J Am Heart Assoc ; 11(18): e026289, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36102222

RESUMO

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow-up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow-up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73-2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/complicações , Arritmias Cardíacas/epidemiologia , Estudos de Coortes , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Compostos de Sulfonilureia/efeitos adversos
11.
Cardiovasc Diabetol ; 21(1): 169, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050763

RESUMO

Tirzepatide is the first dual GIP/GLP-1 receptor co-agonist approved for the treatment of type 2 diabetes in the USA, Europe, and the UAE. Tirzepatide is an acylated peptide engineered to activate the GIP and GLP-1 receptors, key mediators of insulin secretion that are also expressed in regions of the brain that regulate food intake. Five clinical trials in type 2-diabetic subjects (SURPASS 1-5) have shown that tirzepatide at 5-15 mg per week reduces both HbA1c (1.24 to 2.58%) and body weight (5.4-11.7 kg) by amounts unprecedented for a single agent. A sizable proportion of patients (23.0 to 62.4%) reached an HbA1c of < 5.7% (which is the upper limit of the normal range indicating normoglycaemia), and 20.7 to 68.4% lost more than 10% of their baseline body weight. Tirzepatide was significantly more effective in reducing HbA1c and body weight than the selective GLP-1 RA semaglutide (1.0 mg per week), and titrated basal insulin. Adverse events related to tirzepatide were similar to what has been reported for selective GLP-1RA, mainly nausea, vomiting, diarrhoea, and constipation, that were more common at higher doses. Cardiovascular events have been adjudicated across the whole study program, and MACE-4 (nonfatal myocardial infarction, non-fatal stroke, cardiovascular death and hospital admission for angina) events tended to be reduced over up to a 2 year-period, albeit with low numbers of events. For none of the cardiovascular events analysed (MACE-4, or its components) was a hazard ratio > 1.0 vs. pooled comparators found in a meta-analysis covering the whole clinical trial program, and the upper bounds of the confidence intervals for MACE were < 1.3, fulfilling conventional definitions of cardiovascular safety. Tirzepatide was found to improve insulin sensitivity and insulin secretory responses to a greater extent than semaglutide, and this was associated with lower prandial insulin and glucagon concentrations. Both drugs caused similar reductions in appetite, although tirzepatide caused greater weight loss. While the clinical effects of tirzepatide have been very encouraging, important questions remain as to the mechanism of action. While GIP reduces food intake and body weight in rodents, these effects have not been demonstrated in humans. Moreover, it remains to be shown that GIPR agonism can improve insulin secretion in type 2 diabetic patients who have been noted in previous studies to be unresponsive to GIP. Certainly, the apparent advantage of tirzepatide, a dual incretin agonist, over GLP-1RA will spark renewed interest in the therapeutic potential of GIP in type 2 diabetes, obesity and related co-morbidities.


Assuntos
Diabetes Mellitus Tipo 2 , Polipeptídeo Inibidor Gástrico , Peso Corporal , Doenças Cardiovasculares/epidemiologia , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Controle Glicêmico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Metanálise como Assunto , Redução de Peso
12.
Biomed Pharmacother ; 153: 113517, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076602

RESUMO

Patients with type 2 diabetes mellitus (T2DM) face a high risk of developing cardiovascular diseases. However, traditional hypoglycemic drugs have limited effects on macrovascular complications of the disease. Clinical trials have confirmed that glucagon-like peptide-1 receptor agonists (GLP-1RAs), in addition to their capability of controlling blood glucose, can also decrease the risk of cardiovascular events in T2DM. The protective influence of GLP-1RAs on coronary heart disease and heart failure has been proven in recent clinical studies. Therefore, the international guidelines recommend GLP-1 RAs as the first-line therapy for patients with T2DM having cardiovascular disease. Notwithstanding the widespread clinical application of GLP-1RAs, the underlying mechanisms through which GLP-1RAs exert cardiovascular benefits in patients with DM remain unclear. In this review, we systematically summarize the mechanisms of action of GLP-1RAs responsible for producing favorable effects on the cardiovascular system, beyond their capability of blood glucose regulation. GLP-1RA-mediated cardiovascular protection is manifested through multiple mechanisms, including oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and vascular/cardiac remodeling. The understanding of these mechanisms will facilitate the development of new and promising therapeutic modalities for T2DM. Furthermore, we have identified several promising targets for future research in this area.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Glicemia , Doenças Cardiovasculares/etiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/efeitos adversos
13.
Rev Med Liege ; 77(9): 538-543, 2022 Sep.
Artigo em Francês | MEDLINE | ID: mdl-36082602

RESUMO

Patients with insulin-treated type 1 diabetes (T1D) are exposed to hypoglycaemia, which may be serious. Serious cognitive impairment (including coma and seizure) that requires the help of a third party is a medical emergency. Besides the intravenous injection of glucose by a health care provider, its treatment consists of the subcutaneous or intramuscular injection of glucagon which may be performed by a family member. However, such an injection is not easy and puts off some people, which retards the initiation of a potentially life-saving therapy. The intranasal administration of 3 mg glucagon has been shown as efficacious as the subcutaneous or intramuscular injection of 1 mg glucagon in controlled studies carried out in both adult and youth patients with T1D. Stimulation and real-life studies among caregivers, patients and acquaintances showed a preference for nasal glucagon because of its easy and quick use. The launch of nasal glucagon (Baqsimi®) offers new perspectives for the ambulatory emergency management of severe hypoglycaemia and hypoglycaemic coma with a special obvious advantage in children.


La personne avec un diabète de type 1 (DT1) traité par insuline est exposée à un risque d'hypoglycémie, parfois grave. L'hypoglycémie sévère qui désigne tout trouble cognitif grave (y compris coma, convulsion) nécessitant l'intervention d'un tiers est une urgence médicale. Outre l'injection de glucose par voie intraveineuse, réservée à un personnel de santé, le traitement consiste en l'injection de glucagon par voie sous-cutanée ou intramusculaire qui peut être réalisée par un membre de l'entourage. Cependant, cette injection n'est pas aisée et rebute certaines personnes, ce qui retarde la mise en route d'un traitement potentiellement salvateur. L'administration nasale de glucagon 3 mg s'est avérée aussi performante que l'injection sous-cutanée ou intramusculaire de 1 mg dans des études contrôlées réalisées chez des patients DT1 adultes ou enfants/adolescents. Des études de simulation et de vraie vie réalisées auprès de soignants, de patients et de connaissances ont montré une préférence pour la forme nasale en raison de sa facilité et rapidité d'utilisation. La commercialisation du glucagon nasal (Baqsimi®) offre de nouvelles perspectives pour le traitement d'urgence ambulatoire de l'hypoglycémie sévère et du coma, avec un avantage particulièrement évident chez les enfants.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Adulto , Glicemia , Criança , Coma/induzido quimicamente , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucagon/efeitos adversos , Glucagon/uso terapêutico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina
14.
Artigo em Inglês | MEDLINE | ID: mdl-36078769

RESUMO

We conducted this study to determine the effect of metformin use on the risk of new-onset chronic urticaria in patients with type 2 diabetes (T2D). In total, 24,987 pairs of metformin users and nonusers were identified with propensity score-matching from Taiwan's National Health Insurance Research Database from 1 January 2000, to 31 December 2017. Multivariable Cox proportional hazards models were used to compare the risks of chronic urticaria development, severe chronic urticaria, and hospitalization for chronic urticaria between metformin users and nonusers. Compared with metformin nonuse, the aHRs (95% CI) for metformin use in chronic urticaria development, severe chronic urticaria, and hospitalization for chronic urticaria were 1.56 (1.39-1.74), 0.40 (0.12-1.30), and 1.45 (0.82-2.56), respectively. The cumulative incidence of chronic urticaria development was significantly higher in metformin users than in nonusers (p < 0.0001). A longer average cumulative duration of metformin use was associated with higher risks of new-onset and hospitalization for chronic urticaria than metformin nonuse. This nationwide cohort study showed that metformin use was associated with a significantly higher risk of chronic urticaria development. A longer average cumulative duration of metformin use was associated with a higher risk of outcomes. More prospective studies are needed to verify our results.


Assuntos
Urticária Crônica , Diabetes Mellitus Tipo 2 , Metformina , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipoglicemiantes/efeitos adversos , Incidência , Metformina/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
15.
Front Endocrinol (Lausanne) ; 13: 962385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060938

RESUMO

Introduction: The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to facilitate insulin secretion by reducing glucagon and inhibiting glucagon like peptides. With a vague consensus, the advantageous and non-inferior effects of evogliptin relative to other DPP-4i drugs were recently demonstrated on hemoglobin A1c (HbA1c) levels and overall adverse events in T2DM patients. Thus, the aim was to evaluate the overall influence of evogliptin on HbA1c levels and the adverse events in T2DM patients compared to sitagliptin and linagliptin. Methods: Complying with PRISMA guidelines, we conducted a systematic literature search in databases and a meta-analysis. Data about HbA1c levels and the adverse events of T2DM patients were collected and analyzed. Results: From 1,397 studies, we found five matched studies involving 845 subjects (mean age: 54.7 ± 3 years). The meta-analysis revealed that evogliptin was non-inferior to sitagliptin/linagliptin with a mean difference of 0.062 (95% CI: -0.092 to 0.215. I2: 0%. P = 0.431) regarding the HbA1c level reduction, and the risk ratio was -0.006 (95% CI: -0.272 to 0.260. I2: 1.7%. P = 0.966) regarding the adverse effects, indicating no significant difference between evogliptin and linagliptin or sitagliptin in affecting the HbA1c level and adverse effects. Conclusion: The study provides preliminary evidence regarding the similarity in the efficacy of evogliptin compared to other DPP-4i drugs, including sitagliptin and linagliptin, for managing HbA1c levels and adverse events.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Linagliptina/uso terapêutico , Pessoa de Meia-Idade , Piperazinas , Fosfato de Sitagliptina/efeitos adversos
16.
Medicine (Baltimore) ; 101(34): e30072, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36042668

RESUMO

BACKGROUND: New hypoglycemic agents include sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP1RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is). The association between each class of these new hypoglycemic drugs and the risks of various digestive system diseases is unknown. We aimed to explore this relationship by performing a meta-analysis. METHODS: We included large randomized trials of SGLT2is, GLP1RAs, and DPP4is. Outcomes of interest were 91 kinds of digestive diseases including 75 kinds of gastrointestinal disorders and 16 kinds of hepatobiliary disorders. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis was conducted according to 3 different drug classes. RESULTS: We included 21 large trials in this meta-analysis. Compared with placebo, GLP1RAs were associated with the higher risks of gastric ulcer hemorrhage (RR 2.68, 95% CI 1.07-6.68; Pdrug = .035; I2 = 0), pancreatitis (RR 1.48, 95% CI 1.02-2.15; Pdrug = .041; I2 = 0), cholangitis acute (RR 5.96, 95% CI 1.04-34.08; Pdrug = .045; I2 = 0), and cholecystitis acute (RR 1.52, 95% CI 1.08-2.15; Pdrug = .017; I2 = 1.5%), but were not significantly associated with the occurrences of the other 87 kinds of digestive diseases (Pdrug ranged from .064 to .999). SGLT2is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .077 to .995). DPP4is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .085 to .999). CONCLUSIONS: Neither SGLT2is nor DPP4is are associated with the occurrences of various kinds of digestive diseases, whereas GLP1RAs are associated with the higher risks of 4 kinds of digestive diseases, namely, gastric ulcer hemorrhage, pancreatitis, cholangitis acute, and cholecystitis acute. These findings seem to suggest that GLP1RAs are not applicable for patients at high risk of 4 specific digestive diseases, whereas SGLT2is and DPP4is are safe for patients susceptible to digestive diseases. However, our findings require to be further verified by future studies with sufficient statistical power.


Assuntos
Colangite , Colecistite , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Pancreatite , Inibidores do Transportador 2 de Sódio-Glicose , Úlcera Gástrica , Colangite/complicações , Colecistite/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Hipoglicemiantes/efeitos adversos , Pancreatite/induzido quimicamente , Pancreatite/complicações , Pancreatite/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Úlcera Gástrica/tratamento farmacológico
17.
Pharmacol Res ; 183: 106396, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35970329

RESUMO

BACKGROUND AND AIMS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) may have important benefits for the elderly with type 2 diabetes (T2D), however some safety concerns still limit their use in patients over 70 years of age. The SOLD study (SGLT2i in Older Diabetic patients) is a multicenter study, aimed to evaluate the effectiveness and safety of SGLT2i in the older diabetic patients in a real-life setting. MATERIALS AND METHODS: We analyzed a population of 739 adults (mean age 75.4 ± 3.9 years, M/F 420/319) with T2D, which started a SGLT2i-based treatment after the age of 70, with at least one year of follow-up. Data were collected at baseline, at 6 and 12 months of follow-up. RESULTS: SGLT2i (37.5% Empagliflozin, 35.7% Dapagliflozin, 26.1% Canagliflozin, 0.7% Ertugliflozin) were an add-on therapy to Metformin in 88.6%, to basal insulin in 36.1% and to other antidiabetic drugs in 29.6% of cases. 565 subjects completed the follow up, while 174 (23.5%) discontinued treatment due to adverse events which were SGLT2i related. A statistically significant reduction of glycated hemoglobin (baseline vs 12 months: 7.8 ± 1.1 vs 7.1 ± 0.8%, p < 0.001) and body mass index values (baseline vs 12 months: 29.2 ± 4.7 vs 28.1 ± 4.5 kg/m2, p < 0.001) were evident during follow-up. Overall, estimated glomerular filtration rate remained stable over time, with significant reduction of urinary albumin excretion. In the subgroup of patients which were ≥ 80 years, a significant improvement in glycated hemoglobin values without renal function alterations was evident. Overall discontinuation rate during the follow-up period was different across age groups, being urinary tract infections and worsening of renal function the most common cause. CONCLUSION: SGLT2i are well-tolerated and safe in the elderly and appear as an effective therapeutic option, though some caution is also suggested, especially in more fragile subjects.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Idoso de 80 Anos ou mais , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Segurança do Paciente , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
18.
Int J Mol Sci ; 23(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35955455

RESUMO

Metformin, a molecule belonging to the biguanide family, represents one of the most commonly prescribed medications for the treatment of diabetes mellitus in the world. Over the sixty years during which it has been used, many benefits have been described, which are not limited to the treatment of diabetes mellitus. However, since metformin is similar to other members of the same drug family, there is still much concern regarding the risk of lactic acidosis. This article aims to highlight the correlation between the use of metformin and the onset of renal damage or lactic acidosis. Metformin-associated lactic acidosis exists; however, it is rare. The appropriate use of the drug, under safe conditions, induces benefits without risks.


Assuntos
Acidose Láctica , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Metformina , Acidose Láctica/induzido quimicamente , Acidose Láctica/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medo , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos
19.
Nutrients ; 14(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35956334

RESUMO

A previous animal study demonstrated that the administration of Omija extract and soybean mixture (OSM) improved glycemic control in the type 2 diabetes model. In this study, we conducted a 12-week, randomized, double-blinded, and placebo-controlled clinical trial to determine the effects of OSM in humans with hyperglycemia. Participants with fasting plasma concentrations of 100-140 mg/dL were enrolled (n = 80) and administered either OSM or placebo products for 12 weeks. The outcomes included measurements of efficacy (fasting plasma glucose (FPG), postprandial glucose (PPG), fasting plasma insulin (FPI), postprandial insulin (PPI), hemoglobin A1c (HbA1c), C-peptide, fructosamine, and lipid parameters) and safety at baseline and at 12 weeks. After the intervention, the OSM group showed significantly decreased levels of FPG, PPG (30, 60 min), PPI (60 min), insulin area under the curve (AUC), fructosamine, and low-density-lipoprotein (LDL) cholesterol compared to the placebo group. No clinically significant changes in any safety parameter were observed. Therefore, it is hypothesized that OSM supplementation is an effective and safe functional food supplement for humans with hyperglycemia.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Schisandra , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Frutosamina , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Insulina
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