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1.
Diabetes Metab J ; 45(3): 326-336, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33866775

RESUMO

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and ß-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.


Assuntos
Diabetes Mellitus Tipo 2 , Tiazolidinedionas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Pirimidinas , Tiazolidinedionas/efeitos adversos
2.
Osteoporos Int ; 32(9): 1705-1712, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33594487

RESUMO

The population-based cohort study used the Korean National Health Insurance claims database to evaluate the effect of anti-diabetic drugs on osteoporosis. The use of DPP-IV inhibitors does not increase the risk of osteoporosis compared with the use of sulfonylureas in patients with type 2 diabetes mellitus, while a weak association was found between thiazolidinediones and increased risk of osteoporosis. PURPOSE: The current study aimed to evaluate the effect of dipeptidyl peptidase IV inhibitors (DPP-IVi), thiazolidinedione (TZD), and sulfonylurea (SU) on osteoporosis in patients with type 2 diabetes. METHODS: A population-based cohort study was conducted in the Republic of Korea using the Korean National Health Insurance claims database. Data from 2012 to 2017 for patients of 50-99 years of age who were prescribed DPP-IVi, TZD, or SU during 2013-2015 were extracted from the database. Based on pre-defined criteria, a total of 381,404 patients were analyzed after inverse probability of treatment weighting. The association between the study drugs and osteoporosis was estimated using Cox proportional hazards models. Data of 220,166 patients who were prescribed DPP-IVi, 18,630 who were prescribed TZD, and 142,608 patients who were prescribed SU were set. RESULTS: In the multivariate-adjusted analysis, the hazard ratio (HR) of osteoporosis in the DPP-IVi group was not significantly different from that of the SU group (HR: 0.97; 95% confidence interval (CI) 0.94-1.00), whereas the HR of osteoporosis in the TZD group was higher (HR: 1.13; 95% CI 1.06-1.20). In the subgroup analysis, the HRs of osteoporosis were higher with pioglitazone (HR: 1.14; 95% CI 1.06-1.23) in the TZD group and with glibenclamides (HR: 1.39; 95% CI 1.09-1.77) in the SU group, whereas drugs with lower HR in the DPP-IVi group were saxagliptin (HR: 0.93; 95% CI 0.87-0.99) and sitagliptin (HR: 0.93; 95% CI 0.89-0.97). CONCLUSION: DPP-IV inhibitors do not increase the risk of osteoporosis compared with sulfonylureas in patients with type 2 diabetes mellitus, while a weak association was found between thiazolidinediones and increased risk of osteoporosis.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Osteoporose , Tiazolidinedionas , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Tiazolidinedionas/efeitos adversos
3.
Liver Int ; 41(1): 110-122, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33124143

RESUMO

BACKGROUND& AIMS: Type 2 diabetes mellitus (T2DM) management in patients with cirrhosis is complicated. No clinical trials have investigated appropriate antidiabetic drug use in these patients. This study compared the risks of all-cause mortality, major adverse cardiovascular events (MACE) and hepatic outcomes between patients with T2DM and cirrhosis using and not using thiazolidinedione (TZD). METHODS: We selected 1,705 propensity score-matched TZD users and nonusers from a Taiwan National Health Insurance Research Database cohort of T2DM patients with compensated cirrhosis between January 1, 2000, and December 31, 2012 and followed them until December 31, 2013. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risks of investigated outcomes for TZD users. RESULTS: MACE incidence rates during follow-up were 2.14 and 1.30 per 100 patient-years for TZD users and nonusers, respectively (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI], 1.32-2.19). On the basis of TZD use, the aHRs (95% CIs) for stroke, ischemic heart disease and heart failure were 1.81 (1.28-2.55), 1.59 (1.03-2.44) and 2.09 (1.22-3.60) respectively. Compared with TZD nonusers, rosiglitazone users had significantly higher aHR [1.67 (1.26-2.20)] and pioglitazone users had no significant difference of aHR [1.12 (0.90-1.64)]. All-cause mortality, hepatocellular carcinoma, decompensated cirrhosis and hepatic failure risks did not differ significantly between TZD users and nonusers. CONCLUSIONS: Compared with nonuser, TZD users demonstrated significantly higher MACE risks. Therefore, the risks of cardiovascular complications should be considered when prescribing TZDs to patients with T2DM and cirrhosis.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Tiazolidinedionas , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Hipoglicemiantes/efeitos adversos , Cirrose Hepática/epidemiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Tiazolidinedionas/efeitos adversos
4.
Expert Opin Pharmacother ; 22(2): 229-240, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33054481

RESUMO

INTRODUCTION: Diabetes mellitus is one of the most prevalent comorbidities identified in patients with coronavirus disease 2019 (COVID-19). This article aims to discuss the pharmacotherapeutic considerations for the management of diabetes in hospitalized patients with COVID-19. AREAS COVERED: We discussed various aspects of pharmacotherapeutic management in hospitalized patients with COVID-19: (i) susceptibility and severity of COVID-19 among individuals with diabetes, (ii) glycemic goals for hospitalized patients with COVID-19 and concurrent diabetes, (iii) pharmacological treatment considerations for hospitalized patients with COVID-19 and concurrent diabetes. EXPERT OPINION: The glycemic goals in patients with COVID-19 and concurrent type 1 (T1DM) or type 2 diabetes (T2DM) are to avoid disruption of stable metabolic state, maintain optimal glycemic control, and prevent adverse glycemic events. Patients with T1DM require insulin therapy at all times to prevent ketosis. The management strategies for patients with T2DM include temporary discontinuation of certain oral antidiabetic agents and consideration for insulin therapy. Patients with T2DM who are relatively stable and able to eat regularly may continue with oral antidiabetic agents if glycemic control is satisfactory. Hyperglycemia may develop in patients with systemic corticosteroid treatment and should be managed upon accordingly.


Assuntos
COVID-19/terapia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Corticosteroides/efeitos adversos , Glicemia/metabolismo , COVID-19/complicações , Comorbidade , Desprescrições , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Suscetibilidade a Doenças , Controle Glicêmico , Hospitalização , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Incretinas/efeitos adversos , Incretinas/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêutico , Monitorização Fisiológica , Planejamento de Assistência ao Paciente , SARS-CoV-2 , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico
5.
Sci Rep ; 10(1): 17545, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067519

RESUMO

Little is known about gender-specific reporting of adverse events (AEs) associated with antidiabetic drugs. This study was to assess the gender-related difference in AEs reporting associated with antidiabetic agents. The number of antidiabetic drug-AE pairs associated was identified using the Korea Adverse Event Reporting System database. Prevalence of diabetes was estimated using the Health Insurance Review and Assessment Service-National Patients Sample database. Reporting rate per 10,000 people was calculated by dividing drug-AE pairs with the number of antidiabetic drug users by gender. Gender difference was presented with risk ratio (reporting rate ratio) of women to men. Antidiabetic agent-associated AEs were more frequently reported by women than men throughout body organs and drug classes. 13 out of 17 system organ class level disorders with significant gender differences were reported more often by women than men. By drug class, gender-specific reporting rates were observed in most of the drug classes, especially in newer classes such as glucagon-like peptide-1 analog (GLP1-RA), sodium glucose co-transporter-2 inhibitor (SGLT2i), and thiazolidinedione (TZD). Looking into preferred term level for each drug class, women dominated the reports of class-specific AEs of newer antidiabetic drugs such as urinary tract/genital infection (all reported by women) in SGLT2i, edema in TZD (risk ratio (RR) 12.56), and hyperglycemia in insulin users (RR 15.35). Gender differences in antidiabetic-associated AE reporting often attributed to women. Explanations for these different report levels by gender should be further investigated.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Fatores Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Tiazolidinedionas/efeitos adversos
6.
Vnitr Lek ; 66(2): 121-125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32942898

RESUMO

Pioglitazone belongs to the drugs primarily reducing insulin resistance. Currently, it is the only insulin sensitizer available. In addition to hypoglycaemic action, it has a number of other metabolically beneficial effects that are responsible for its positive effect on the vascular wall. The paper provides an overview of cardiovascular clinical trials with pioglitazone, its safety profile and practical recommendations for its administration.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Tiazolidinedionas , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Pioglitazona , Tiazolidinedionas/efeitos adversos
7.
Cochrane Database Syst Rev ; 8: CD009966, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32803882

RESUMO

BACKGROUND: Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. OBJECTIVES: To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). AUTHORS' CONCLUSIONS: The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adamantano/efeitos adversos , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Viés , Causas de Morte , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Jejum/sangue , Hemoglobina A Glicada/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Pioglitazona , Complicações Pós-Operatórias/etiologia , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fosfato de Sitagliptina/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Transplantados , Vildagliptina
8.
Diabetes Care ; 43(10): 2493-2499, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32801130

RESUMO

OBJECTIVE: To evaluate the association between metformin use and anemia risk in type 2 diabetes, and the time-course for this, in a randomized controlled trial (RCT) and real-world population data. RESEARCH DESIGN AND METHODS: Anemia was defined as a hemoglobin measure of <11 g/dL. In the RCTs A Diabetes Outcome Progression Trial (ADOPT; n = 3,967) and UK Prospective Diabetes Study (UKPDS; n = 1,473), logistic regression was used to model anemia risk and nonlinear mixed models for change in hematological parameters. In the observational Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) population (n = 3,485), discrete-time failure analysis was used to model the effect of cumulative metformin exposure on anemia risk. RESULTS: In ADOPT, compared with sulfonylureas, the odds ratio (OR) (95% CI) for anemia was 1.93 (1.10, 3.38) for metformin and 4.18 (2.50, 7.00) for thiazolidinediones. In UKPDS, compared with diet, the OR (95% CI) was 3.40 (1.98, 5.83) for metformin, 0.96 (0.57, 1.62) for sulfonylureas, and 1.08 (0.62, 1.87) for insulin. In ADOPT, hemoglobin and hematocrit dropped after metformin initiation by 6 months, with no further decrease after 3 years. In UKPDS, hemoglobin fell by 3 years in the metformin group compared with other treatments. At years 6 and 9, hemoglobin was reduced in all treatment groups, with no greater difference seen in the metformin group. In GoDARTS, each 1 g/day of metformin use was associated with a 2% higher annual risk of anemia. CONCLUSIONS: Metformin use is associated with early risk of anemia in individuals with type 2 diabetes, a finding consistent across two RCTs and replicated in one real-world study. The mechanism for this early fall in hemoglobin is uncertain, but given the time course, is unlikely to be due to vitamin B12 deficiency alone.


Assuntos
Anemia/induzido quimicamente , Anemia/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/efeitos adversos , Adulto , Idoso , Conjuntos de Dados como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Dinâmica não Linear , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Fatores de Risco , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/efeitos adversos , Reino Unido/epidemiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-32532851

RESUMO

INTRODUCTION: This study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin-sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin. RESEARCH DESIGN AND METHODS: We assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin-sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models. RESULTS: Over a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p<0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively. CONCLUSIONS: For patients with T2DM on metformin-sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Neoplasias , Tiazolidinedionas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Metformina/efeitos adversos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Estudos Retrospectivos , Tiazolidinedionas/efeitos adversos , Resultado do Tratamento
10.
Sci Rep ; 10(1): 5746, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238842

RESUMO

While basal insulin remains the most effective antidiabetic agent and substantially reduces the risk of hypoglycemia, few studies have examined the comparative effect of basal insulin in the real-world setting. This study aimed to assess the outcomes of adding basal insulin compared with thiazolidinediones (TZDs) or dipeptidyl peptidase-4 inhibitors (DPP-4is) as a third antidiabetic agent in patients with type 2 diabetes mellitus (T2DM). A retrospective cohort study involving T2DM was conducted with health administrative data in Taiwan. Patients starting a third antidiabetic agent after receiving a metformin-containing dual combination were identified. The study endpoints included composite major adverse cardiovascular events (MACEs), all-cause mortality, and hypoglycemia. Propensity score matching and Cox modeling were used for analysis. After matching, the basal insulin and TZD groups contained 6,101 and 11,823 patients, respectively, and the basal insulin and DPP-4i groups contained 6,051 and 11,900 patients, respectively. TZDs and DPP-4is were both associated with similar risks of MACEs and hypoglycemia but a lower risk of all-cause mortality than basal insulin (TZDs: HR 0.55, 95% CI 0.38-0.81; DPP-4is: HR 0.56, 95% CI 0.39-0.82). Further studies are needed to elucidate the findings of increased all-cause mortality risk in patients receiving basal insulin, especially those with advanced diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan/epidemiologia , Tiazolidinedionas/efeitos adversos , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(17): e19833, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332631

RESUMO

The study aimed to investigate the association between the risk of hepatocellular carcinoma and thiazolidinediones use among type 2 diabetic patients who had risk factors for hepatocellular carcinoma.A population-based case-control study was performed using the database of the Taiwan National Health Insurance Program. The cases consisted of 23580 type 2 diabetic subjects aged 20 to 84 years with newly diagnosed hepatocellular carcinoma between 2000 and 2011. The sex- and age-matched controls consisted of 23580 randomly selected type 2 diabetic subjects without hepatocellular carcinoma between 2000 and 2011. Ever use of thiazolidinediones was defined as subjects who had at least 1 prescription of thiazolidinediones before the index date. Never use of thiazolidinediones was defined as subjects who did not have a prescription of thiazolidinediones before the index date. The odds ratio and 95% confidence interval for the association between hepatocellular carcinoma and cumulative duration of thiazolidinediones use was measured by a multivariable logistic regression model.Among subjects with any 1 of the comorbidities including alcohol-related disease, cirrhosis, hepatitis B infection, hepatitis C infection, and other chronic hepatitis, a multivariable logistic regression model demonstrated that there was a negative association between hepatocellular carcinoma and every 1-year increase of cumulative duration of thiazolidinediones use (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97).There was a negative association in a duration-dependent manner between the risk of hepatocellular carcinoma and thiazolidinediones use among type 2 diabetic patients who had risk factors for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/uso terapêutico , Neoplasias Hepáticas/epidemiologia , Tiazolidinedionas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Tiazolidinedionas/efeitos adversos , Adulto Jovem
12.
Curr Diabetes Rev ; 16(8): 851-858, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32026779

RESUMO

BACKGROUND: The vast majority of individuals diagnosed with diabetes are low/middle income and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost: metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide, glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or dose-related. OBJECTIVE: We conducted a narrative review of low-cost OHMs. METHODS: We evaluated the maximum recommended (MAX) compared to the most effective (EFF) daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic medications. RESULTS: We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000 mg, EFF: 1,500-2,000/1,500-2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide (MAX: 20 mg, EFF: 2.5-5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in HbA1c levels occurred at weeks 12-20 (sulfonylureas), 25-39 (metformin), and 25 (pioglitazone). Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses (p<0.05). Glimepiride and pioglitazone have been successfully used in renal impairment. CONCLUSION: Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Administração Oral , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulinas/administração & dosagem , Insulinas/efeitos adversos , Insulinas/economia , Insulinas/uso terapêutico , Metformina/administração & dosagem , Metformina/efeitos adversos , Metformina/economia , Metformina/uso terapêutico , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/economia , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/economia , Tiazolidinedionas/uso terapêutico
14.
J Hepatol ; 72(4): 613-626, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31697972

RESUMO

BACKGROUND & AIMS: MSDC-0602K is a novel insulin sensitizer designed to preferentially target the mitochondrial pyruvate carrier while minimizing direct binding to the transcriptional factor PPARγ. Herein, we aimed to assess the efficacy and safety of MSDC-0602K in patients with non-alcoholic steatohepatitis. METHODS: Patients with biopsy-confirmed NASH and fibrosis (F1-F3) were randomized to daily oral placebo, or 1 of 3 MSDC-0602K doses in a 52-week double-blind study. The primary efficacy endpoint was hepatic histological improvement of ≥2 points in non-alcoholic fatty liver disease activity score (NAS) with a ≥1-point reduction in either ballooning or lobular inflammation and no increase in fibrosis stage at 12 months. Secondary endpoints included NAS improvement without worsening fibrosis, NASH resolution, and fibrosis reduction. Exploratory endpoints included changes in insulin sensitivity, liver injury and liver fibrosis markers. RESULTS: Patients were randomly assigned to placebo (n = 94), or 62.5 mg (n = 99), 125 mg (n = 98), or 250 mg (n = 101) of MSDC-0602K. At baseline, glycated hemoglobin was 6.4 ±â€¯1.0%, 61.5% of patients had fibrosis F2/F3 and the average NAS was 5.3. The primary endpoint was reached in 29.7%, 29.8%, 32.9% and 39.5% of patients in the placebo, 62.5 mg, 125 mg and 250 mg dose arms, respectively, with adjusted odds ratios relative to placebo of 0.89 (95% CI 0.44-1.81), 1.22 (95% CI 0.60-2.48), and 1.64 (95% CI 0.83-3.27). The 2 highest doses of MSDC-0602K led to significant reductions in glucose, glycated hemoglobin, insulin, liver enzymes and NAS compared to placebo. The incidence of hypoglycemia and PPARγ-agonist-associated events such as edema and fractures were similar in the placebo and MSDC-0602K groups. CONCLUSIONS: MSDC-0602K did not demonstrate statistically significant effects on primary and secondary liver histology endpoints. However, effects on non-invasive measures of liver cell injury and glucose metabolism support further exploration of MSDC-0602K's safety and potential efficacy in patients with type 2 diabetes and liver injury. [ClinicalTrials.gov Identifier: NCT02784444]. LAY SUMMARY: First-generation insulin sensitizers are used to treat type 2 diabetes, but are associated with side effects including edema, bone fractures, and hypoglycemia. MSDC-0602K is a second-generation insulin sensitizer designed to reduce these side effects. We hypothesized that insulin sensitization could improve non-alcoholic steatohepatitis. In the current study of patients with non-alcoholic steatohepatitis, MSDC-0602K did not demonstrate significant effects on liver histology with the biopsy techniques used. However, useful information was gained for the design of future studies and MSDC-0602K significantly decreased fasting glucose, insulin, glycated hemoglobin, and markers of liver injury without dose-limiting side effects.


Assuntos
Acetofenonas/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Tiazolidinedionas/efeitos adversos , Acetofenonas/administração & dosagem , Administração Oral , Adulto , Idoso , Aspartato Aminotransferases/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/sangue , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Tiazolidinedionas/administração & dosagem , Resultado do Tratamento
15.
Diabet Med ; 37(2): 248-255, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31365143

RESUMO

AIM: To compare weight change in a lifestyle-based weight management programme between participants taking weight-gaining, weight-neutral/loss and mixed diabetes medications. METHODS: Electronic health records for individuals (≥ 18 years) with Type 2 diabetes who had been referred to a non-surgical weight management programme between February 2008 and May 2014 were studied. Diabetes medications were classified into three categories based on their effect on body weight. In this intervention cohort study, weight change was calculated for participants attending two or more sessions. RESULTS: All 998 individuals who took oral diabetes medications and attended two or more sessions of weight management were included. Some 59.5% of participants were women, and participants had a mean BMI of 41.1 kg/m2 (women) and 40.2 kg/m2 (men). Of the diabetes medication combinations prescribed, 46.0% were weight-neutral/loss, 41.3% mixed and 12.7% weight-gaining. The mean weight change for participants on weight-gaining and weight-neutral/loss diabetes medications respectively was -2.5 kg [95% confidence interval (CI) -3.2 to -1.8) and -3.3 kg (95% CI -3.8 to -2.9) (P = 0.05) for those attending two or more sessions (n = 998). Compared with those prescribed weight-neutral medications, participants prescribed weight-gaining medication lost 0.86 kg less (95% CI 0.02 to 1.7; P = 0.045) in a model adjusted for age, sex, BMI and socio-economic status. CONCLUSIONS: Participants on weight-neutral/loss diabetes medications had a greater absolute weight loss within a weight management intervention compared with those on weight-gaining medications. Diabetes medications should be reviewed ahead of planned weight-loss interventions to help ensure maximal effectiveness of the intervention.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade/terapia , Perda de Peso , Programas de Redução de Peso , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Hipoglicemiantes/classificação , Incretinas/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Obesidade/complicações , Manejo da Obesidade , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Ganho de Peso , Adulto Jovem
16.
Physiol Res ; 68(Suppl 2): S107-S120, 2019 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-31842574

RESUMO

Patients with diabetes mellitus are at an increased risk of bone fractures. Several groups of effective antidiabetic drugs are available, which are very often given in combination. The effects of these medications on bone metabolism and fracture risk must not be neglected. Commonly used antidiabetic drugs might have a positive, neutral or negative impact on skeletal health. Increased risk of fracture has been identified with use of thiazolidinediones, most definitively in women. Also treatment with sulfonylureas can have adverse effects on bone. One consequence of these findings has been greater attention to fracture outcomes in trails of new diabetes medication (incretins and SGLT-2 inhibitors). The effect of insulin on bone is discussed and the risk of fractures in patients using insulin seems to be unrelated to insulin as itself. The aim of the review is to summarize effects of antidiabetic treatment on bone - bone mineral density, fractures and bone turnover markers. The authors also try to recommend a strategy how to treat patients with diabetes mellitus regarding the risk of osteoporotic fractures. In this review the problem of how to treat osteoporosis in patient with diabetes is also discussed.


Assuntos
Osso e Ossos/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Animais , Conservadores da Densidade Óssea/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Humanos , Incretinas/farmacologia , Insulina/farmacologia , Metformina/farmacologia , Osteoporose/complicações , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Compostos de Sulfonilureia/efeitos adversos , Tiazolidinedionas/efeitos adversos
17.
Curr Diab Rep ; 19(12): 151, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776781

RESUMO

PURPOSE OF REVIEW: Thiazolidinediones (TZDs) are the only pharmacologic agents that specifically treat insulin resistance. The beneficial effects of TZDs on the cardiovascular risk factors associated with insulin resistance have been well documented. TZD use has been limited because of concern about safety issues and side effects. RECENT FINDINGS: Recent studies indicate that cardiovascular toxicity with rosiglitazone and increase in bladder cancer with pioglitazone are no longer significant issues. There are new data which show that pioglitazone treatment reduces myocardial infarctions and ischemic strokes. New data concerning TZD-mediated edema, congestive heart failure, and bone fractures improves the clinician's ability to select patients that will have minimal significant side effects. Thiazolidinediones are now generic and less costly than pharmaceutical company-promoted therapies. Better understanding of the side effects coupled with clear benefits on the components of the insulin resistance syndrome should promote TZD use in treating patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Tiazolidinedionas/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Resistência à Insulina , Pioglitazona/efeitos adversos , Pioglitazona/uso terapêutico , Rosiglitazona/efeitos adversos , Rosiglitazona/uso terapêutico , Tiazolidinedionas/efeitos adversos
19.
Molecules ; 24(19)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590284

RESUMO

The thiazolidinedione 49 (TD49) is an effective algaecide against harmful algae; however, its potential effects on the immune function of the edible bay scallop are unclear. Therefore, the present work studied the effects of TD49 on the immune response in bay scallop by evaluating activities of acid phosphatase (ACP), alkaline phosphatase (ALP), and superoxide dismutase (SOD), as well as nitric oxide (NO) levels, total protein content, and expression of immune genes (CTL-6, PGRP, PrxV, MT, and Cu/Zn-SOD) at 3-48 h post-exposure (hpe) to TD49. The activities of ACP and ALP significantly increased in TD49-treated groups at 3-24 hpe, whereas NO levels decreased significantly in 0.58 and 0.68 µM of TD49 at 6-24 hpe, after which the level was similar to that in the untreated control. Moreover, SOD activity significantly increased in all three concentration groups at 3-6 hpe, while it decreased at 12 hpe in the 0.68 µM TD49 treatment group. Notably, total protein content increased with TD49 treatment at each time interval. The results revealed that variable effects on the expression of immune-related genes were observed after treatment with TD49. The findings demonstrate that exposure of scallops to TD49 changes immune responses and expression of immune-related genes. We hypothesize that TD49 may disrupt immune system in bay scallop. The current investigation highlights the potential negative effects of using TD49 as an algaecide on marine economic bivalves to control harmful algal blooms in marine environments.


Assuntos
Herbicidas/efeitos adversos , Pectinidae/imunologia , Tiazolidinedionas/efeitos adversos , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Herbicidas/química , Imunidade/efeitos dos fármacos , Pectinidae/efeitos dos fármacos , Pectinidae/metabolismo , Frutos do Mar , Superóxido Dismutase/metabolismo , Tiazolidinedionas/química
20.
Diabetes Care ; 42(11): 2065-2074, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31471377

RESUMO

OBJECTIVE: A recent study raises concerns that dipeptidyl peptidase 4 inhibitors (DPP4i) are associated with increased risk of inflammatory bowel disease (IBD). We evaluated the association between new use of DPP4i and IBD risk compared with other second-line antihyperglycemics. RESEARCH DESIGN AND METHODS: We implemented an active-comparator, new-user cohort design using two U.S. administrative claims databases for commercially insured (MarketScan) and older adult (Medicare fee-for-service, 20% random sample) patients from January 2007 to December 2016. We identified patients, aged ≥18 years, who initiated DPP4i versus sulfonylureas (SUs) or initiated DPP4i versus thiazolidinediones (TZDs) and were without prior diagnosis, treatment, or procedure for IBD. The primary outcome was incident IBD, defined by IBD diagnosis preceded by colonoscopy and biopsy and followed by IBD treatment. We performed propensity score weighting to control for measured baseline confounding, estimated adjusted hazard ratios (aHRs [95% CI]) using weighted Cox proportional hazards models, and used random-effects meta-analysis models to pool aHRs across cohorts. RESULTS: We identified 895,747 eligible patients initiating DPP4i, SU, or TZD; IBD incidence rates ranged from 11.6 to 32.3/100,000 person-years. Over a median treatment duration of 1.09-1.69 years, DPP4i were not associated with increased IBD risk across comparisons. The pooled aHRs for IBD were 0.82 (95% CI 0.41-1.61) when comparing DPP4i (n = 161,612) to SU (n = 310,550) and 0.76 (0.46-1.26) when comparing DPP4i (n = 205,570) to TZD (n = 87,543). CONCLUSIONS: Our population-based cohort study of U.S. adults with diabetes suggests that short-term DPP4i treatment does not increase IBD risk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hipoglicemiantes/efeitos adversos , Doenças Inflamatórias Intestinais/epidemiologia , Compostos de Sulfonilureia/efeitos adversos , Tiazolidinedionas/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Masculino , Medicare , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
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