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AIM: The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon-like peptide-1 analogue for type 2 diabetes, in healthy Chinese subjects. MATERIALS AND METHODS: This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC0-24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose. RESULTS: Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0-24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders. CONCLUSIONS: At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide.
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Glicemia , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Humanos , Peptídeos Semelhantes ao Glucagon/farmacocinética , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/farmacologia , Masculino , Método Duplo-Cego , Adulto , Feminino , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Administração Oral , Glicemia/efeitos dos fármacos , China , Adulto Jovem , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Povo Asiático , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Área Sob a Curva , Peso Corporal/efeitos dos fármacos , População do Leste AsiáticoRESUMO
INTRODUCTION: Time in range (TIR) is a metric of glycaemic target management derived from continuous glucose monitoring (CGM) data. This study aimed to understand knowledge of and attitudes towards use of TIR among healthcare professionals (HCPs), and gain insights into benefits and barriers to its use in clinical practice. METHODS: An online survey was disseminated across seven countries. Participants were sampled from online HCP panels and were aware of TIR (defined as amount of time in, below, and above target range). Participants were HCPs classified as specialists (SP), generalists (GP), or allied HCPs (AP; diabetes nurse specialists, diabetes educators, general nurses, nurse practitioners/physician assistants). RESULTS: Respondents included 741 SP, 671 GP and 307 AP. Most HCPs (approximately 90%) agreed TIR is likely/somewhat likely to become the standard of diabetes management. Perceived benefits of TIR included helping to optimise medication regimen (SP, 71%; GP, 73%; AP, 74%), giving HCPs the knowledge and insights to make informed clinical decisions (SP, 66%; GP, 61%; AP, 72%), and empowering people with diabetes with information to successfully manage their diabetes (SP, 69%; GP, 77%; AP, 78%). Barriers to wider adoption included limited CGM access (SP, 65%; GP, 74%; AP, 69%) and lack of HCP training/education (SP, 45%; GP, 59%; AP, 51%). Most participants considered integration of TIR into clinical guidelines, recognition of TIR by regulators as a primary clinical endpoint, and recognition of TIR by payers as a parameter for diabetes treatment evaluation as key factors for increased use. CONCLUSIONS: Overall, HCPs agreed on the benefits of using TIR for diabetes management. Besides raising awareness among HCPs and people with diabetes, more training and healthcare system updates are needed to facilitate increased TIR use. In addition, integration into clinical guidelines and recognition by regulators and payers are needed.
'Time in range' is the proportion of time in a day that a person's glucose level is within a particular range. The purpose of this study was to understand knowledge of and attitudes towards use of TIR among healthcare professionals. The study was carried out using an online survey and participants from seven countries were included. Participants were healthcare professionals classified as specialists (SP), generalists (GP), or allied healthcare professionals (AP; diabetes nurse specialists, diabetes educators, general nurses, nurse practitioners, or physician assistants). Overall, 1719 participants were included in the study. Most healthcare professionals (approximately 90%) agreed that time in range is likely/somewhat likely to become the standard of diabetes management. Participants reported the following benefits of time in range: helping to optimise medication regimen, giving healthcare professionals the knowledge and insights to make informed clinical decisions, and empowering people with diabetes with information to successfully manage their diabetes. The most common barrier to wider time in range adoption was limited access to continuous glucose monitoring (SP, 65%; GP, 74%; AP, 69%), followed by lack of healthcare professionals' training/education (SP, 45%; GP, 59%; AP, 51%). Most participants considered integration of time in range into clinical guidelines, recognition of time in range by regulators as a primary clinical endpoint, and recognition of time in range by payers as a parameter for evaluation of diabetes treatment as key factors for the increased use of time in range.
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INTRODUCTION: Hypertension is a progressive cardiovascular condition arising from complex aetiologies. Progression is strongly associated with functional and structural abnormalities that lead to multi-organ dysfunction. Stroke and myocardial infarction are two of the major complications of hypertension in India. Various anti-hypertensive drugs, such as calcium channel blockers (CCBs), beta-blockers, diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have been the medications of choice for disease management and are known to be effective in reducing the complications of hypertension. CCBs, such as amlodipine, are also currently being used and proven to be effective, although their beneficial effects in the management of complications of hypertension like stroke and myocardial infarction (MI) have yet to be proven. Therefore, the aim of this systematic review was to evaluate the effect of amlodipine on stroke and MI in hypertensive patients. METHODS: A systematic search of English electronic databases was performed for studies with sufficient statistical power that were published between 2000 andl 30 August 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A total of 676 papers were screened, and 13 were found eligible to be included in the meta-analysis. Studies that included patients who suffered from MI or stroke and were under amlodipine treatment were included in the analysis. The odds ratio and the risk ratio of amlodipine compared to active control/placebo were noted from the studies and statistically analyzed. RESULTS: Amlodipine had a significant effect in reducing stroke and MI in hypertensive patients. Similar to results published in reports, this systematic review proved that the hazard ratio for amlodipine was < 1 for stroke (0.69-1.04) and MI (0.77-0.98), showing that amlodipine accounted for better prevention of stroke and MI. CONCLUSION: In the pooled analysis of data from 12 randomised controlled trials and one double-blinded cohort study measuring the effect of CCBs, we found that the CCB amlodipine reduced the risk of stroke and MI in hypertensive patients. Superior results for amlodipine were found in ten of the 13 studies included in this meta-analysis.
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BACKGROUND: Early use of combination therapy in diabetes patients may lead to sustained glycemic control and thereby reduce the progression of diabetic complications. Given the limitation of the traditional stepwise intensification strategy, early combination therapy can be an effective approach. Therefore, this study aims to assess the real-world efficacy of a combination of metformin and vildagliptin in comparison to metformin alone in type 2 diabetes mellitus (T2DM) patients in India. METHODS: This was an observational, retrospective, non-interventional study based on electronic medical records (EMRs) of 2740 T2DM patients, retrieved from 2010 onwards from 22 diabetes centres across India. Adult drug naïve patients with a 5-year history of T2DM treated with either metformin or a combination of metformin and vildagliptin for at least 3 months were considered for this study. Efficacy assessment was done to evaluate the post-treatment HbA1c levels and patients requiring additional oral antidiabetic drugs (OADs) at the time of follow-up visit. Patients were also analyzed for the occurrence of adverse events. RESULTS: Out of the total, 2452 patients were in metformin only arm, and 288 patients were in metformin plus vildagliptin treatment arm. A more significant reduction in HbA1c level was observed in metformin plus vildagliptin arm than metformin only arm (median: -0.5% vs 0%, respectively; p<0.001). Patients requiring additional OAD at follow-up were significantly lesser in the metformin plus vildagliptin arm than the metformin only arm (15.6% vs 35.2%, respectively; p<0.001). The adverse events were comparable across the two arms, and commonly reported adverse events were giddiness, fatigue and gastric discomfort. CONCLUSION: The findings of this EMR-based real-world study emphasizes the need for early initiation of combination therapy (metformin plus vildagliptin) over metformin monotherapy for achieving better glycemic control.