RESUMO
In community nursing, the administration of insulin for people with type 2 diabetes can be delegated by registered nurses to healthcare support workers. Although a voluntary framework in England provides national guidance, little is known about its uptake. The project aim was to determine the roll-out, characteristics and support needs in relation to the delegation of insulin administration in community settings. An online survey was disseminated to community nursing services in England via social media and nursing networks. Of the 115 responding organisations, 81% (n=93) had an insulin delegation programme, with most initiated since 2018. From these services, 41% (n=3704) of insulin injections were delegated daily, with benefits for patients, staff and services reported, along with some challenges. Delegation of insulin administration is an established and valued initiative. Awareness of the national voluntary framework is increasing. National guidance is considered important to support governance arrangements and safety.
Assuntos
Enfermagem em Saúde Comunitária, Diabetes Mellitus Tipo 2, Insulina, Humanos, Inglaterra, Insulina/administração & dosagem, Insulina/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/enfermagem, Inquéritos e Questionários, Medicina Estatal, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Delegação Vertical de Responsabilidades ProfissionaisRESUMO
PURPOSE: This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. METHODS: Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. RESULTS: The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. CONCLUSIONS: The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.
Assuntos
Compostos Benzidrílicos, Diabetes Mellitus Tipo 2, Glucosídeos, Metformina, Pancreatite, Compostos de Sulfonilureia, Humanos, Compostos Benzidrílicos/efeitos adversos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/epidemiologia, Pancreatite/induzido quimicamente, Pancreatite/epidemiologia, Glucosídeos/efeitos adversos, Glucosídeos/uso terapêutico, Glucosídeos/administração & dosagem, Compostos de Sulfonilureia/efeitos adversos, Compostos de Sulfonilureia/uso terapêutico, Masculino, Feminino, Pessoa de Meia-Idade, Idoso, Metformina/efeitos adversos, Metformina/administração & dosagem, Metformina/uso terapêutico, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/administração & dosagem, Bases de Dados Factuais, Incidência, Vigilância de Produtos Comercializados/estatística & dados numéricos, Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Adulto, Estados Unidos/epidemiologia, Pontuação de PropensãoRESUMO
OBJECTIVE: Tirzepatide is an injectable peptide approved by the US Food and Drug Administration for the treatment of Type 2 diabetes (T2DM). Its weight-loss effect primarily targets fat reduction; however, such effect on patients with chronic kidney disease (CKD) undergoing haemodialysis (HD) has not been reported. METHODS: Nine patients with CKD undergoing HD received weekly tirzepatide doses (2.5-7.5 mg) once a week. Evaluations encompassed tirzepatide's impact on dry weight (DW) and body composition assessed at baseline and study conclusion using bioelectrical impedance analysis. This longitudinal study included nine patients, with a median age of 53 years and median HD duration of 4 years. RESULTS: Tirzepatide treatment significantly decreased glycated albumin compared with the value at baseline (22.7 ± 5.4 vs. 18.3 ± 2.5%, p = 0.028, respectively). Significant reductions were observed in DW (-1.0 kg, p = 0.024) and body mass index (-0.6 kg/m2, p = 0.050) following tirzepatide administration. Total fat mass was also reduced, but not significantly (- 2.51% from baseline, p = 0.214). In contrast, skeletal muscle mass was not decreased (-1.02% from baseline, p = 0.722). No serious side effects other than nausea were observed during the study period. CONCLUSION: Tirzepatide effectively provides good glycaemic control in T2DM patients undergoing HD, decreasing DW by reducing body fat mass without increasing frailty risk.
Assuntos
Diabetes Mellitus Tipo 2, Controle Glicêmico, Diálise Renal, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Pessoa de Meia-Idade, Masculino, Feminino, Estudos Retrospectivos, Controle Glicêmico/métodos, Adulto, Idoso, Composição Corporal, Insuficiência Renal Crônica/terapia, Insuficiência Renal Crônica/complicações, Glicemia/metabolismo, Estudos Longitudinais, Hipoglicemiantes/administração & dosagemAssuntos
Diabetes Mellitus Tipo 2, Peptídeos Semelhantes ao Glucagon, Hipoglicemiantes, Humanos, Peptídeos Semelhantes ao Glucagon/uso terapêutico, Peptídeos Semelhantes ao Glucagon/efeitos adversos, Peptídeos Semelhantes ao Glucagon/administração & dosagem, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/administração & dosagemRESUMO
BACKGROUND: The efficacy and safety of lobeglitazone sulfate has been reported only in the Korean population, and no study has been conducted in India. MATERIALS AND METHODS: In this 16-week randomized, double-blind, and multicenter study, the efficacy and safety of lobeglitazone sulfate 0.5 mg were evaluated with pioglitazone 15 mg. Type 2 diabetes mellitus (T2DM) patients with ≥7.5% glycated hemoglobin (HbA1c) ≤10.5% and on stable metformin dose were assigned to both treatment arms. The primary outcome was a mean change in HbA1c. Safety assessments included adverse events (AE), home-based glucose monitoring, vital parameters, electrocardiogram (ECG), and laboratory assessments. RESULTS: A total of 328 subjects were randomized equally in two groups. A statistically significant reduction in HbA1c at week 16 in the lobeglitazone group with the least square (LS) mean change: 1.01 [standard error (SE): 0.09] (p < 0.0001) was seen. The LS mean difference between the two groups was 0.05 (SE: 0.12) [95% confidence interval (CI): -0.18, 0.27], which was statistically significant (p = 0.0013). Statistically significant reductions were also observed in fasting and postprandial glucose. Treatment-emergent Aes (TEAE) were comparable between both groups. CONCLUSION: Lobeglitazone 0.5 mg once daily was found to be efficacious and safe in the treatment of T2DM in the Indian population. Lobeglitazone significantly improved glycemic parameters and was noninferior to pioglitazone; hence, it could be a promising insulin sensitizer in T2DM management in India.
Assuntos
Diabetes Mellitus Tipo 2, Quimioterapia Combinada, Hemoglobinas Glicadas, Hipoglicemiantes, Metformina, Pioglitazona, Tiazolidinedionas, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Metformina/uso terapêutico, Metformina/administração & dosagem, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/efeitos adversos, Masculino, Pessoa de Meia-Idade, Método Duplo-Cego, Feminino, Tiazolidinedionas/uso terapêutico, Tiazolidinedionas/administração & dosagem, Hemoglobinas Glicadas/análise, Índia, Pioglitazona/uso terapêutico, Pioglitazona/administração & dosagem, Glicemia/análise, Glicemia/efeitos dos fármacos, Adulto, Resultado do Tratamento, Idoso, PirimidinasAssuntos
Peptídeos Semelhantes ao Glucagon, Hipoglicemiantes, Humanos, Peptídeos Semelhantes ao Glucagon/efeitos adversos, Peptídeos Semelhantes ao Glucagon/administração & dosagem, Peptídeos Semelhantes ao Glucagon/uso terapêutico, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
OBJECTIVE: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. DESIGN: Cohort study emulating a comparative effectiveness trial (target trial). SETTING: Linked primary care, hospital, and death data in England, 2015-21. PARTICIPANTS: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. MAIN OUTCOME MEASURES: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. RESULTS: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). CONCLUSIONS: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.
Assuntos
Diabetes Mellitus Tipo 2, Inibidores da Dipeptidil Peptidase IV, Hemoglobinas Glicadas, Hipoglicemiantes, Metformina, Inibidores do Transportador 2 de Sódio-Glicose, Compostos de Sulfonilureia, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Masculino, Feminino, Pessoa de Meia-Idade, Compostos de Sulfonilureia/uso terapêutico, Compostos de Sulfonilureia/administração & dosagem, Idoso, Metformina/uso terapêutico, Metformina/administração & dosagem, Hemoglobinas Glicadas/análise, Hemoglobinas Glicadas/metabolismo, Inibidores da Dipeptidil Peptidase IV/uso terapêutico, Inibidores da Dipeptidil Peptidase IV/administração & dosagem, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem, Administração Oral, Taxa de Filtração Glomerular/efeitos dos fármacos, Inglaterra/epidemiologia, Quimioterapia Combinada, Resultado do Tratamento, Estudos de Coortes, Pesquisa Comparativa da Efetividade, Índice de Massa Corporal, Pressão Sanguínea/efeitos dos fármacosRESUMO
Insulin is the cornerstone of treatment in type 1 diabetes mellitus. However, because of its protein structure, insulin has to be administered via injection, and many attempts have been made to create oral formulations, especially using nanoparticles (NPs). The aim of this study was to compare the hypoglycemic effect of insulin-loaded NPs to that of subcutaneous insulin in an in vivo rat model of diabetes. We used biodegradable D-α-tocopherol polyethylene glycol succinate-emulsified, chitosan-capped poly(lactic-co-glycolic acid) NPs loaded with soluble human insulin in a dose of 20 IU/kg body weight, and examined the physical characteristics of NPs in vivo and in vitro. Serum glucose levels were reduced after 6 h, but the difference was not significant compared to subcutaneous insulin; at 12 h and 24 h, insulin levels were significantly higher in rats treated with NPs than in rats treated with subcutaneous insulin. There was no significant difference in serum insulin levels at 12 h and 24 h compared to non-diabetic rats. Our findings suggest that chitosan-based NPs are able to maintain good glycemic control for up to 24 h and can be considered a potential carrier for oral insulin delivery.
Assuntos
Diabetes Mellitus Experimental, Hiperglicemia, Insulina, Nanopartículas, Estreptozocina, Animais, Diabetes Mellitus Experimental/tratamento farmacológico, Diabetes Mellitus Experimental/sangue, Insulina/sangue, Insulina/administração & dosagem, Ratos, Administração Oral, Masculino, Hiperglicemia/tratamento farmacológico, Quitosana/química, Glicemia, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Modelos Animais de Doenças, Ratos Sprague-DawleyRESUMO
BACKGROUND: Lifestyle changes, especially regarding diet quality and physical activity, are important in the management of type 2 diabetes (T2D). This mixed-methods study explores self-initiated lifestyle changes in patients with T2D who followed a periodic fasting-mimicking diet (FMD). METHODS: Quantitative data were obtained from the Fasting In diabetes Treatment trial (November 2018 to August 2021) in which 100 participants with T2D, using metformin only or no medication, were randomised to receive a monthly 5-day FMD for twelve months next to usual care, or usual care only. Diet quality and physical activity questionnaires were completed at baseline, six and twelve months. Changes over time were analysed using linear mixed models. Focus groups were organized with FMD participants to explore experiences regarding self-initiated lifestyle changes. The qualitative data was analysed using the Theoretical Domains Framework. RESULTS: Questionnaires were available from 49 FMD participants and 43 controls. No differences in diet quality were found. Total physical activity in the FMD participants changed from 34.6 to 38.5 h per week (h/wk) from baseline to twelve months, while in controls it changed from 34.9 to 29.0 h/wk (between group difference, p = 0.03). In six focus groups with FMD participants (n = 20), individual participants perceived the FMD as an encouragement for (minor) lifestyle changes. There were no barriers to behaviour change related to the FMD. Important facilitators of healthy behaviour were an increase in awareness of the impact of lifestyle on health (knowledge), better physical fitness (physical) and health improvement (reinforcement). Facilitators unrelated to the FMD included family support (social influences) and opportunities in the neighbourhood (environmental context and resources), while barriers unrelated to the FMD were experiencing health problems (physical) and social events (social influences). CONCLUSIONS: Using an FMD for five consecutive days per month did not affect diet quality in between FMD periods in quantitative analysis, but increased the number of hours per week spent on physical activity. Qualitative analysis revealed self-initiated improvements in both diet quality and physical activity in individual participants using an FMD. Healthcare professionals could use an FMD programme as a 'teachable moment' to stimulate additional lifestyle changes. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03811587. Registered 22 January 2019.
Assuntos
Diabetes Mellitus Tipo 2, Exercício Físico, Jejum, Humanos, Diabetes Mellitus Tipo 2/dietoterapia, Diabetes Mellitus Tipo 2/psicologia, Masculino, Feminino, Pessoa de Meia-Idade, Jejum/fisiologia, Exercício Físico/fisiologia, Exercício Físico/psicologia, Idoso, Estilo de Vida, Grupos Focais, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Metformina/uso terapêutico, Dieta, Inquéritos e QuestionáriosRESUMO
BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.
Assuntos
Automonitorização da Glicemia, Glicemia, Diabetes Mellitus Tipo 1, Hemoglobinas Glicadas, Estudos Multicêntricos como Assunto, Ensaios Clínicos Pragmáticos como Assunto, Humanos, Diabetes Mellitus Tipo 1/sangue, Diabetes Mellitus Tipo 1/tratamento farmacológico, Diabetes Mellitus Tipo 1/diagnóstico, Automonitorização da Glicemia/instrumentação, Quênia, Glicemia/metabolismo, Glicemia/análise, Glicemia/efeitos dos fármacos, Hemoglobinas Glicadas/metabolismo, Hemoglobinas Glicadas/análise, África do Sul, Qualidade de Vida, Controle Glicêmico/instrumentação, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/efeitos adversos, Ciência da Implementação, Insulina/administração & dosagem, Insulina/uso terapêutico, Resultado do Tratamento, Análise Custo-Benefício, Monitoramento Contínuo da GlicoseRESUMO
Oral dispersible films have received broad interest due to fast drug absorption and no first-path metabolism, leading to high bioavailability and better patient compliance. Saxagliptin (SXG) is an antidiabetic drug that undergoes first-path metabolism, resulting in a less active metabolite, so the development of SXG oral dispersible films (SXG-ODFs) improves SXG bioavailability. The formula optimisation included a response surface experimental design and the impact of three formulation factors, the type and concentration of polymer and plasticiser concentration on in-vitro disintegration time and folding endurance. Two optimised SXG-ODFs prepared using either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose were investigated. SXG-ODFs prepared with PVA demonstrated a superior rapid disintegration time, ranging from 17 to 890 s, with the fastest disintegration time recorded at 17 s. These short durations can be attributed to the hydrophilic nature of PVA, facilitating rapid hydration and disintegration upon contact with saliva. Additionally, PVA-based films displayed remarkable folding endurance, surpassing 200 folds without rupture, indicating flexibility and stability. The high tensile strength of PVA-based films further underscores their robust mechanical properties, with tensile strength values reaching up to 4.53 MPa. SXG exhibits a UV absorption wavelength of around 212 nm, posing challenges for traditional quantitative spectrophotometric analysis, so a polyaniline nanoparticles-based solid-contact screen-printed ion-selective electrode (SP-ISE) was employed for the determination of SXG release profile effectively in comparison to HPLC. SP-ISE showed a better real-time release profile of SXG-ODFs, and the optimised formula showed lower blood glucose levels than commercial tablets.
Assuntos
Adamantano, Compostos de Anilina, Dipeptídeos, Liberação Controlada de Fármacos, Nanopartículas, Álcool de Polivinil, Adamantano/química, Adamantano/análogos & derivados, Dipeptídeos/química, Dipeptídeos/farmacocinética, Dipeptídeos/administração & dosagem, Compostos de Anilina/química, Nanopartículas/química, Administração Oral, Álcool de Polivinil/química, Hipoglicemiantes/química, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/farmacocinética, Humanos, Derivados da Hipromelose/química, Resistência à Tração, Química Farmacêutica/métodos, Disponibilidade Biológica, Solubilidade, EletrodosRESUMO
INTRODUCTION-AIM: Flexible insulin therapy is currently considered the gold standard therapy of type 1 diabetes. We aimed to study the evolution of glycemic control, weight and nutritional intake of a group of patients with type 1 diabetes, three months after the initiation of functional insulin therapy (FIT). METHODS: This was a prospective longitudinal study having included 30 type 1 diabetic patients hospitalized for education to FIT. Each patient underwent an assessment of glycemic control (glycated hemoglobin (A1C) and number of hypoglycemia), weight and nutritional intake before FIT and 3 months after the initiation of this educative approach. RESULTS: The mean age of patients was 21,8 ± 7,9 years and the sex ratio was 0,5. The mean duration of diabetes was 7,2 ± 6 years. Three months after initiation of FIT, we observed a significant lowering of A1C, which went from 9,2 ± 1,6% to 8,3 ± 1,4% (p<0,001) of the number of minor hypoglycemia (p=0,001) and that of severe hypoglycemia (p= 0,021). the average weight went from 64,6 ± 13,1 kg to 65,5 ± 13,5 kg (p = 0,040) with a significant increase in BMI (p = 0,041). Weight gain was observed in 67% of patients. This weight gain contrasted with a significant decrease in caloric (p = 0,040) and in carbohydrates intakes (p = 0,027). CONCLUSION: Weight gain, associated with better glycemic control, should encourage the healthcare team to strengthen therapeutic education of patients undergoing FIT in order to limit weight gain.
Assuntos
Peso Corporal, Diabetes Mellitus Tipo 1, Hipoglicemiantes, Insulina, Humanos, Diabetes Mellitus Tipo 1/tratamento farmacológico, Diabetes Mellitus Tipo 1/sangue, Feminino, Masculino, Insulina/administração & dosagem, Insulina/uso terapêutico, Adulto, Adulto Jovem, Estudos Prospectivos, Estudos Longitudinais, Adolescente, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/uso terapêutico, Peso Corporal/fisiologia, Hemoglobinas Glicadas/análise, Hemoglobinas Glicadas/metabolismo, Hipoglicemia/prevenção & controle, Hipoglicemia/induzido quimicamente, Hipoglicemia/epidemiologia, Controle Glicêmico/métodos, Ingestão de Energia, Aumento de Peso/fisiologia, Aumento de Peso/efeitos dos fármacos, Fatores de Tempo, Glicemia/análise, Glicemia/metabolismoRESUMO
OBJECTIVE: Obesity presents an enduring and multifaceted dilemma that impacts individuals, society, economies, and healthcare systems alike. Glucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, have received FDA approval for obesity treatment. This study aims to present a cost-effectiveness analysis to compare the cost and clinical outcomes of semaglutide vs. liraglutide on weight loss in people with overweight and obesity. MATERIALS AND METHODS: A cost-effectiveness analysis was conducted to compare the cost and the clinical outcomes of adding weekly 2.4 mg SC semaglutide vs. daily 3.0 mg SC liraglutide or placebo to physical activity and diet control in overweight and obese patients. A clinical outcome of achieving ≥15% weight loss was chosen. A simple decision analysis model from a third-payer perspective was applied. Drug costs were based on the retail price of the USA market. One-way sensitivity analyses were performed. RESULTS: Results showed that 2.4 mg weekly semaglutide, when added to physical activity and diet control, was the most cost-effective choice in terms of ≥15% weight loss (ICER: $ 7,056/patient/68 weeks). The model was robust against the 50% increase in the unit cost of semaglutide and the 50% decrease in the unit cost of liraglutide, as well as the changes in probabilities by the corresponding 95% confidence intervals across the model. CONCLUSIONS: This cost-effectiveness analysis suggests that employing once-weekly 2.4 mg semaglutide emerges as a remarkably cost-effective option when contrasted with once-daily 3.0 mg liraglutide in patients with overweight and obesity when added to physical activity and diet control.
Assuntos
Análise Custo-Benefício, Peptídeos Semelhantes ao Glucagon, Liraglutida, Obesidade, Sobrepeso, Humanos, Peptídeos Semelhantes ao Glucagon/economia, Peptídeos Semelhantes ao Glucagon/administração & dosagem, Peptídeos Semelhantes ao Glucagon/uso terapêutico, Liraglutida/administração & dosagem, Liraglutida/economia, Liraglutida/uso terapêutico, Obesidade/tratamento farmacológico, Obesidade/economia, Sobrepeso/tratamento farmacológico, Sobrepeso/economia, Injeções Subcutâneas, Técnicas de Apoio para a Decisão, Redução de Peso/efeitos dos fármacos, Esquema de Medicação, Fármacos Antiobesidade/economia, Fármacos Antiobesidade/administração & dosagem, Fármacos Antiobesidade/uso terapêutico, Hipoglicemiantes/economia, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/uso terapêutico, Análise de Custo-EfetividadeRESUMO
Insulin resistance complicates diabetes care. Its effectiveness and tolerability as an addition to metformin, DPP4 inhibitor and insulin treatment in type 2 diabetic patients will be examined in this research. Participants with type 2 diabetes from poor socio-economic backgrounds had HbA1c values ≥8.5% when using Insulin+Metformin+DPP-4 inhibitors. They received 10mg Empagliflozin daily for 12 weeks (n=143). The main outcome was change in HbA1c at 12th week from baseline. Secondary outcomes were baseline weight and week 12 FPG. Adjusted mean (SE) HbA1c increases at week 12 were: Mean ± SD 10.38 (6.8-17.0) vs. Mean±SD 9.05±1.77 (5.60-16.0) with empagliflozin 10mg. When added to the regimen, empagliflozin significantly reduced FPG, systolic and diastolic blood pressure. The mean (SE) BMI increases from baseline were 31.28±5.89 (16.0-66.0) and 29.73±5.47 (3.0-46.0) with 10mg empagliflozin. Two individuals experienced urinary tract infections as AEs, but no genital infections. Adding empagliflozin 10mg daily to metformin+DPP4 inhibitor+insulin improved glycemic control, body weight and blood pressure for 12 weeks. The intervention was well-tolerated, highlighting empagliflozin's therapeutic potential.
Assuntos
Compostos Benzidrílicos, Diabetes Mellitus Tipo 2, Quimioterapia Combinada, Glucosídeos, Hipoglicemiantes, Insulina, Metformina, Obesidade, Humanos, Glucosídeos/efeitos adversos, Glucosídeos/administração & dosagem, Glucosídeos/uso terapêutico, Compostos Benzidrílicos/efeitos adversos, Compostos Benzidrílicos/uso terapêutico, Compostos Benzidrílicos/administração & dosagem, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/sangue, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/administração & dosagem, Pessoa de Meia-Idade, Masculino, Feminino, Metformina/administração & dosagem, Metformina/uso terapêutico, Metformina/efeitos adversos, Obesidade/tratamento farmacológico, Hemoglobinas Glicadas/metabolismo, Resultado do Tratamento, Glicemia/efeitos dos fármacos, Glicemia/metabolismo, Adulto, Idoso, Administração Oral, Inibidores da Dipeptidil Peptidase IV/uso terapêutico, Inibidores da Dipeptidil Peptidase IV/efeitos adversos, Inibidores da Dipeptidil Peptidase IV/administração & dosagem, Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
Pioglitazone is class of thiazolidinediones that activates peroxisome proliferator-activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone-induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach. All subjects received 30 mg of pioglitazone once daily in the assigned sequence and period. Urine samples were collected before pioglitazone administration and for 24 h after 7 days of administration. A total of 1465 compounds were detected and filtered using a coefficient of variance below 30% and 108 metabolites were significantly altered upon pioglitazone administration via multivariate statistical analysis. Fourteen significant metabolites were identified using authentic standards and public libraries. Additionally, pathway analysis revealed that metabolites from purine and beta-alanine metabolisms were significantly altered after pioglitazone administration. Further analysis of quantification of metabolites from purine metabolism, revealed that the xanthine/hypoxanthine and uric acid/xanthine ratios were significantly decreased at post-dose. Pioglitazone-dependent endogenous metabolites and metabolic ratio indicated the potential effect of pioglitazone on the activation of PPAR and fatty acid synthesis. Additional studies involving patients are required to validate these findings.
Assuntos
Voluntários Saudáveis, Pioglitazona, Purinas, Tiazolidinedionas, Humanos, Masculino, Pioglitazona/farmacologia, Pioglitazona/administração & dosagem, Purinas/administração & dosagem, Purinas/metabolismo, Adulto, Tiazolidinedionas/administração & dosagem, Tiazolidinedionas/farmacologia, Tiazolidinedionas/efeitos adversos, Metabolômica/métodos, Adulto Jovem, Hipoglicemiantes/farmacologia, Hipoglicemiantes/administração & dosagemRESUMO
Aim: To evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China. Methods: This was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups. Results: A total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303). Conclusion: URLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.
Assuntos
Automonitorização da Glicemia, Glicemia, Diabetes Mellitus Tipo 2, Hipoglicemiantes, Insulina Lispro, Período Pós-Prandial, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/sangue, Insulina Lispro/uso terapêutico, Insulina Lispro/administração & dosagem, Masculino, Feminino, Pessoa de Meia-Idade, Glicemia/análise, China/epidemiologia, Método Duplo-Cego, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Automonitorização da Glicemia/métodos, Estudos Prospectivos, Controle Glicêmico/métodos, Adulto, Idoso, Hemoglobinas Glicadas/análise, Quimioterapia CombinadaRESUMO
BACKGROUND: There is a rising prevalence of type 2 diabetes among older people. This population also suffers from co-morbidity and a greater number of diabetes related complications, such as visual and cognitive impairment, which can potentially affect their ability to manage insulin regimens. Understanding the experiences of older people when they transition to insulin will help the development of healthcare interventions to enhance their diabetes outcomes, overall health and quality of life. AIMS: The aims of this exploratory study were to (1) understand the experiences of older people with type 2 diabetes in relation to insulin treatment initiation and management and (2) use this understanding to consider how the insulin management support provided to older people by healthcare providers could be more tailored to their needs. METHOD: A qualitative study using semi structured (remote) interviews with older people with diabetes (n = 10) and caregivers (n = 4) from the UK. Interviews were audio recorded and transcribed, and framework analysis was used to analyse the data. RESULTS: Three main themes, along with six subthemes, were generated from the study data. Participants generally felt at ease with insulin administration following training, yet some reported feelings of failure at transitioning to insulin use. Participants were also frustrated at what they perceived were insufficient resources for effective self-management, coupled with a lack of professional interest in optimising their health as older people. Some also expressed dissatisfaction regarding the brevity of their consultations, inconsistent information from different healthcare professionals and poor treatment coordination between primary and secondary care. CONCLUSION: Overall, the study emphasised that older people need better support, education and resources to help manage their insulin use. Healthcare professionals should be encouraged to adopt a more individualised approach to supporting older people that acknowledges their prior knowledge, physical and psychological capabilities and motivation for diabetes self-management. In addition, better communication between different services and greater access to specialist support is clearly needed for this older population. PRACTICE IMPLICATIONS: An integrated care pathway for insulin use in older people could be considered. This would include an assessment of the older person's needs and capacity on their initiation to insulin; targeted education and training in self-management; timely access to appropriate emotional and peer support resources; care plans developed collaboratively with patients; and individualised glucose targets that recognise the needs and preferences of the older person.
Assuntos
Diabetes Mellitus Tipo 2, Hipoglicemiantes, Insulina, Pesquisa Qualitativa, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/psicologia, Idoso, Masculino, Feminino, Insulina/uso terapêutico, Insulina/administração & dosagem, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Idoso de 80 Anos ou mais, Autogestão/psicologia, Reino Unido, Pessoa de Meia-Idade, Cuidadores/psicologia, Entrevistas como Assunto, Qualidade de Vida/psicologiaRESUMO
The 5xFAD mouse model shows age-related weight loss as well as cognitive and motor deficits. Metabolic dysregulation, especially impaired insulin signaling, is also present in AD. This study examined whether intranasal delivery of insulin (INI) at low (0.875 U) or high (1.750 U) doses would ameliorate these deficits compared to saline in 10-month-old female 5xFAD and B6SJL wildtype (WT) mice. INI increased forelimb grip strength in the wire hang test in 5xFAD mice in a dose-dependent manner but did not improve the performance of 5xFAD mice on the balance beam. High INI doses reduced frailty scores in 5xFAD mice and improved spatial memory in both acquisition and reversal probe trials in the Morris water maze. INI increased swim speed in 5xFAD mice but had no effect on object recognition memory or working memory in the spontaneous alternation task, nor did it improve memory in the contextual or cued fear memory tasks. High doses of insulin increased the liver, spleen, and kidney weights and reduced brown adipose tissue weights. P-Akt signaling in the hippocampus was increased by insulin in a dose-dependent manner. Altogether, INI increased strength, reduced frailty scores, and improved visual spatial memory. Hypoglycemia was not present after INI, however alterations in tissue and organ weights were present. These results are novel and important as they indicate that intra-nasal insulin can reverse cognitive, motor and frailty deficits found in this mouse model of AD.
