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BACKGROUND: Obesity is a major risk factor for many leading causes of illness and death worldwide. Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity. METHODS: In this phase 2, randomized, double-blind trial, we enrolled adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without diabetes. Participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36, or 45 mg) or placebo once daily for 36 weeks. The percentage change from baseline in body weight was assessed at week 26 (primary end point) and at week 36 (secondary end point). RESULTS: A total of 272 participants underwent randomization. At baseline, the mean body weight was 108.7 kg, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.9. At week 26, the mean change from baseline in body weight ranged from -8.6% to -12.6% across the orforglipron dose cohorts and was -2.0% in the placebo group. At week 36, the mean change ranged from -9.4% to -14.7% with orforglipron and was -2.3% with placebo. A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo. The use of orforglipron led to improvement in all prespecified weight-related and cardiometabolic measures. The most common adverse events reported with orforglipron were gastrointestinal events, which were mild to moderate, occurred primarily during dose escalation, and led to discontinuation of orforglipron in 10 to 17% of participants across dose cohorts. The safety profile of orforglipron was consistent with that of the GLP-1 receptor agonist class. CONCLUSIONS: Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists. (Funded by Eli Lilly; GZGI ClinicalTrials.gov number, NCT05051579.).
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Fármacos Antiobesidad , Receptor del Péptido 1 Similar al Glucagón , Obesidad , Pérdida de Peso , Adulto , Humanos , Administración Oral , Fármacos Antiobesidad/administración & dosificación , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Diabetes Mellitus Tipo 2 , Método Doble Ciego , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/inducido químicamente , Pérdida de Peso/efectos de los fármacosRESUMEN
AIMS: Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This review describes the study design and rationale of the efsitora phase 3 Once Weekly (QW) Insulin Therapy (QWINT) clinical development programme, including the five trials, QWINT-1 through QWINT-5. MATERIALS AND METHODS: The five trials included insulin-naïve adults (QWINT-1 and -2) with type 2 diabetes (T2D), adults with T2D previously treated with basal insulin (QWINT-3 and -4), and QWINT-5 in adults with type 1 diabetes. All five trials were designed as multicentre, randomized, controlled, open-label, treat-to-target studies to investigate the efficacy and safety of efsitora versus active once-daily basal insulin comparators (insulin glargine U100 or insulin degludec U100). The primary objective of each trial is to compare the change in HbA1c from baseline to week 26 or 52 between efsitora and the active comparator. The key secondary objectives include change in fasting glucose, insulin dose and continuous glucose monitoring variables, and patient-reported outcome questionnaires. CONCLUSIONS: The QWINT development programme includes a racially and geographically diverse population to provide important information regarding the efficacy and safety of efsitora and its clinical management of people with diabetes.
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Ensayos Clínicos Fase III como Asunto , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Esquema de Medicación , Hipoglucemiantes , Insulina de Acción Prolongada , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Insulina de Acción Prolongada/administración & dosificación , Insulina de Acción Prolongada/uso terapéutico , Glucemia/efectos de los fármacos , Glucemia/análisis , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Adulto , Insulina Glargina/administración & dosificación , Insulina Glargina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Femenino , Masculino , Proyectos de Investigación , Insulina/administración & dosificación , Insulina/uso terapéutico , Estudios Multicéntricos como Asunto , Persona de Mediana EdadRESUMEN
The t:slim X2 insulin pump with Control-IQ technology (Control-IQ) advanced hybrid closed-loop automated insulin delivery system was evaluated in this prospective single-arm trial. Thirty adults with type 2 diabetes using the Control-IQ system showed substantial glycemic improvement with no increase in hypoglycemia. Mean time in range (70-180 mg/dL) improved 15%, representing an increase of 3.6 hours/day, and mean glucose decreased by 22 mg/dL.
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Despite increases in the availability and effectiveness of other therapies, insulin remains an essential treatment for approximately 30 million people with type 2 diabetes worldwide. The development of biosimilars has created the potential for significant health care cost savings and may lead to greater access to basal insulin for vast populations. In this review, we discuss evidence demonstrating equipoise between basal insulin biosimilars and the patented analogs they may replace.
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Rapid-acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra-rapid-acting insulins, including ultra-rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.
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Diabetes Mellitus Tipo 2 , Hipoglucemia , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa/uso terapéutico , Humanos , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Insulina , Insulina Aspart/efectos adversos , Insulina Lispro/uso terapéutico , Insulina Regular Humana/uso terapéutico , Insulina de Acción Corta/uso terapéuticoRESUMEN
OBJECTIVE: The objective of this study was to define an expert opinion on continuous glucose monitoring (CGM) in persons with type 2 diabetes mellitus, including its advantages, barriers, and best clinical practices for initiation, patient-clinician communication, and data management. METHODS: A series of virtual discussions was held to recommend improvements to clinical practice and design clinical tools for primary care clinicians. Participants included endocrinologists, primary care physicians, physician assistants, advanced practice nurses, and diabetes care and education specialists. RESULTS: The expert panels recommended CGM as a supplement to blood glucose monitoring and hemoglobin A1c for managing diabetes in persons with diabetes (PWDs). CGM can help predict potential pitfalls in glycemic management, including hypo and hyperglycemic excursions, which directly influence lifestyle changes, medication initiation, and dosing decisions. A toolkit was designed with practical guidance on the integration of CGM into clinical practice, interpretation of results, clinical guidelines, a patient action plan, and other useful management tools. CONCLUSION: This review summarizes the findings from a roundtable discussion with endocrinology and primary care clinicians, a discussion of the advantages and challenges of CGM, and clinical approaches to improving the care of PWDs. CGM offers more detailed tracking of glucose levels than blood glucose monitoring or hemoglobin A1c, and it can detect asymptomatic hypoglycemia. Specialized education of providers, the cost to patients and providers, and data management are barriers to the widespread adoption of CGM for PWDs.
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Diabetes Mellitus Tipo 2 , Hipoglucemia , Glucemia , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/diagnósticoRESUMEN
OBJECTIVE: To provide evidence-based recommendations regarding the use of advanced technology in the management of persons with diabetes mellitus to clinicians, diabetes-care teams, health care professionals, and other stakeholders. METHODS: The American Association of Clinical Endocrinology (AACE) conducted literature searches for relevant articles published from 2012 to 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established AACE protocol for guideline development. MAIN OUTCOME MEASURES: Primary outcomes of interest included hemoglobin A1C, rates and severity of hypoglycemia, time in range, time above range, and time below range. RESULTS: This guideline includes 37 evidence-based clinical practice recommendations for advanced diabetes technology and contains 357 citations that inform the evidence base. RECOMMENDATIONS: Evidence-based recommendations were developed regarding the efficacy and safety of devices for the management of persons with diabetes mellitus, metrics used to aide with the assessment of advanced diabetes technology, and standards for the implementation of this technology. CONCLUSIONS: Advanced diabetes technology can assist persons with diabetes to safely and effectively achieve glycemic targets, improve quality of life, add greater convenience, potentially reduce burden of care, and offer a personalized approach to self-management. Furthermore, diabetes technology can improve the efficiency and effectiveness of clinical decision-making. Successful integration of these technologies into care requires knowledge about the functionality of devices in this rapidly changing field. This information will allow health care professionals to provide necessary education and training to persons accessing these treatments and have the required expertise to interpret data and make appropriate treatment adjustments.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Humanos , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Calidad de Vida , Tecnología , Estados UnidosRESUMEN
AIMS: To assess the efficacy, insulin dose, safety and immunogenicity when people with type 1 diabetes mellitus switched between MYL-1501D and reference insulin glargine (Lantus®; Sanofi-Aventis US LLC, Bridgewater, New Jersey). MATERIALS AND METHODS: Eligible participants from INSTRIDE 1 who completed 52 weeks of reference insulin glargine treatment were randomized 1:1 to the reference sequence (n = 63; reference insulin glargine for 36 weeks) or to the treatment-switching sequence (n = 64; MYL-1501D [weeks 0-12], reference insulin glargine [weeks 12-24] and MYL-1501D [weeks 24-36]). Change in glycated haemoglobin (HbA1c) from baseline to week 36 was the primary efficacy endpoint used to demonstrate equivalence between the two treatment sequences. Secondary endpoints included: change in fasting plasma glucose (FPG), self-monitored blood glucose (SMBG) and insulin dose; immunogenicity; and adverse events, including hypoglycaemia. RESULTS: Mean changes in HbA1c (least squares [LS] mean [SE]) from baseline to week 36 were -0.05 (0.032) and -0.06 (0.034) for the treatment-switching and reference sequences, respectively (LS mean difference 0.01 [95% CI -0.085 to 0.101]). Treatment sequences were comparable in terms of secondary endpoints, including FPG, SMBG and insulin dose, and the safety and immunogenicity profiles of the two sequences were similar. CONCLUSIONS: Switching participants between MYL-1501D and reference insulin glargine demonstrated equivalent efficacy and similar safety and immunogenicity, showing that people taking reference insulin glargine can safely switch to MYL-1501D.
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Diabetes Mellitus Tipo 1 , Biosimilares Farmacéuticos , Glucemia , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/efectos adversos , Insulina Glargina/efectos adversosRESUMEN
In this post hoc analysis we investigated the effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers in participants in the DUAL II (vs. insulin degludec), DUAL V (vs. insulin glargine 100 units/mL) and DUAL VII (vs. basal-bolus therapy) trials, grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in glycated haemoblogin (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), HDL cholesterol (DUAL VII) and LDL cholesterol (DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in men (DUAL V). Differences in treatment effect were seen between sexes in waist circumference (DUAL II), systolic BP (DUAL II, DUAL V) and triglycerides (DUAL VII), and between diabetes durations in LDL cholesterol (DUAL V). In conclusion, IDegLira is associated with a general improvement in CV risk markers compared with basal insulin or basal-bolus therapy after 26 weeks of treatment.
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Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2 , Hipoglucemiantes/uso terapéutico , Insulina de Acción Prolongada/uso terapéutico , Liraglutida/uso terapéutico , Anciano , Presión Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Combinación de Medicamentos , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Liraglutida/administración & dosificación , Masculino , Persona de Mediana Edad , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
AIMS: To assess the non-inferiority of MYL-1501D, a proposed biosimilar or follow-on biological agent to marketed insulin glargine, to reference insulin glargine (Lantus®; Sanofi-Aventis US LLC, Bridgewater, New Jersey) based on change in glycated hemoglobin (HbA1c). MATERIALS AND METHODS: INSTRIDE 2 was a multicentre, open-label, randomized, parallel-group, phase III non-inferiority study comparing the efficacy and safety of MYL-1501D with those of reference insulin glargine in insulin-naive and insulin-non-naive patients with type 2 diabetes mellitus receiving oral antidiabetic drugs (OADs). The primary efficacy endpoint was change in HbA1c from baseline to week 24. Secondary endpoints included metabolic readouts (eg, changes in fasting plasma glucose, insulin dosage, self-monitored blood glucose), immunogenicity and adverse events, including hypoglycaemia and nocturnal hypoglycaemic events. RESULTS: In all, 560 patients were randomized to MYL-1501D or insulin glargine in combination with OADs for 24 weeks. The mean change in HbA1c from baseline to week 24 was -0.60% (95% CI -0.78, -0.41) and - 0.66% (95% CI -0.84, -0.48) for MYL-1501D and reference insulin glargine, respectively. MYL-1501D was well tolerated and had a safety profile similar to that of reference insulin glargine. CONCLUSIONS: Demonstration of non-inferiority between MYL-1501D and reference insulin glargine for reduction of HbA1c during 24 weeks of treatment was achieved. The two treatment groups were similar in terms of secondary endpoints, including hypoglycaemia and nocturnal hypoglycaemia, local and systemic reactions, other safety variables, and immunogenicity.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes , Insulina Glargina , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Insulina Glargina/efectos adversos , Insulina Glargina/uso terapéutico , Masculino , Persona de Mediana EdadRESUMEN
AIM: To test the safety and efficacy of MYL-1501D, a proposed insulin glargine biosimilar, in patients with type 1 diabetes mellitus (T1DM). METHODS: The safety and efficacy of MYL-1501D and reference insulin glargine were evaluated in INSTRIDE 1, a 52-week, open-label, randomized, phase III study in patients with T1DM. The primary objective was to determine whether once-daily MYL-1501D was non-inferior to once-daily insulin glargine when administered in combination with mealtime insulin lispro based on change in glycated haemoglobin (HbA1c) from baseline to week 24. Secondary endpoints were changes in fasting plasma glucose, insulin dose, self-monitored blood glucose and immunogenicity from baseline, and occurrences of hypoglycaemic, nocturnal hypoglycaemic and adverse events up to week 52. RESULTS: Overall, 558 patients were randomized 1:1 to MYL-1501D or reference insulin glargine in combination with thrice-daily mealtime insulin lispro for 52 weeks. The mean change in HbA1c from baseline to week 24 was 0.14% (standard error [SE] 0.054; 95% confidence interval [CI] 0.033, 0.244) for MYL-1501D and 0.11% (SE 0.054; 95% CI 0.007, 0.220) for reference insulin glargine. MYL-1501D had a safety profile similar to that of reference insulin glargine and was well tolerated in patients with T1DM up to week 52. CONCLUSIONS: The upper 95% CI limit for mean change in HbA1c at week 24 indicated that MYL-1501D was non-inferior to reference insulin glargine. There were no clinically meaningful differences between groups in incidence of overall and nocturnal hypoglycaemia, local or systemic reactions, safety or immunogenicity.
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Biosimilares Farmacéuticos/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina Glargina/uso terapéutico , Actividades Cotidianas , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada/efectos adversos , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemia/fisiopatología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Incidencia , Insulina Glargina/administración & dosificación , Insulina Glargina/efectos adversos , Insulina Lispro/administración & dosificación , Insulina Lispro/uso terapéutico , Comidas , Sobrepeso/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
Dulaglutide (DU) is a once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for the treatment of type 2 diabetes mellitus (T2DM). Glycaemic efficacy and safety characteristics of dulaglutide have been assessed in six Phase 3 studies in the AWARD program. The objective of this review article is to summarize these results from the six completed AWARD studies. At the primary endpoint, in five of the six studies, once weekly dulaglutide 1.5 mg was superior to the active comparator [exenatide, insulin glargine (two studies), metformin, and sitagliptin], with a greater proportion of patients reaching glycated hemoglobin A1c (HbA1c) targets of <7.0% (53.0 mmol/mol) and ≤6.5% (47.5 mmol/mol). Dulaglutide 1.5 mg was non-inferior to liraglutide in AWARD-6. Once weekly dulaglutide 0.75 mg was evaluated in five of these trials and demonstrated superiority to the active comparator in four of five AWARD studies (exenatide, glargine, metformin, and sitagliptin), and non-inferiority to glargine in the AWARD-2 study. Similar to other GLP-1 receptor agonists, treatment with dulaglutide was associated with weight loss or attenuation of weight gain and low rates of hypoglycaemia when used alone or with non-insulin-secretagogue therapy. The most frequently reported adverse events were gastrointestinal, including nausea, vomiting, and diarrhea. The incidence of dulaglutide antidrug antibody formation was 1-2.8% with rare injection site reactions. In conclusion, dulaglutide is an effective treatment for T2DM and has an acceptable tolerability and safety profile. Copyright © 2016 John Wiley & Sons, Ltd.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Animales , Ensayos Clínicos como Asunto , Péptidos Similares al Glucagón/uso terapéutico , Humanos , Seguridad , Resultado del TratamientoRESUMEN
OBJECTIVE: The primary objective was to assess the operative rate in patients with a benign result from the Afirma gene expression classifier (GEC) during long-term follow-up at nonacademic medical facilities. The secondary endpoint of this study was the treating physician's opinion regarding the safety of GEC use compared to the hypothetical situation of providing thyroid nodule management without the GEC. METHODS: This was a retrospective study of nonacademic medical practices utilizing the GEC. Those clinicians utilizing the GEC testing who had three or more 'benign' results during the data collection period (September 2010 through June 2014) were invited to participate. Operative status and patient demographics were documented for patients with GEC testing at least 36 months (± 3 months) prior to the date of data collection. A survey also was administered to the treating physicians to assess their perceived safety of using the GEC in patient care. RESULTS: During 36 months (± 3 months) of follow-up, 17 of 98 patients (17.3%) with a 'benign' GEC result underwent surgery. Within the first 2 years after a 'benign' GEC, 88% of surgeries were performed. Regarding safety of the GEC, the treating physicians reported that patient safety was improved by using the GEC compared to not using the GEC in 78 of 91 cases (86%). CONCLUSION: It appears that a 'benign' result on the GEC is associated with a reduction in the rate of thyroid surgeries compared to published data when patients are followed for 36 months after testing. A nonoperative approach to follow-up was felt to be a safe alternative to diagnostic surgery by the majority of responsible physicians in the study. ABBREVIATIONS: AUS = atypia of undetermined significance FLUS = follicular lesion of undetermined significance FN = follicular neoplasm FNA = fine-needle aspiration GEC = gene expression classifier.
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OBJECTIVE/METHODS: Barriers to continuous glucose monitoring (CGM) use continue to hamper adoption of this valuable technology for the management of diabetes. The American Association of Clinical Endocrinologists and the American College of Endocrinology convened a public consensus conference February 20, 2016, to review available CGM data and propose strategies for expanding CGM access. RESULTS: Conference participants agreed that evidence supports the benefits of CGM in type 1 diabetes and that these benefits are likely to apply whenever intensive insulin therapy is used, regardless of diabetes type. CGM is likely to reduce healthcare resource utilization for acute and chronic complications, although real-world analyses are needed to confirm potential cost savings and quality of life improvements. Ongoing technological advances have improved CGM accuracy and usability, but more innovations in human factors, data delivery, reporting, and interpretation are needed to foster expanded use. The development of a standardized data report using similar metrics across all devices would facilitate clinician and patient understanding and utilization of CGM. Expanded CGM coverage by government and private payers is an urgent need. CONCLUSION: CGM improves glycemic control, reduces hypoglycemia, and may reduce overall costs of diabetes management. Expanding CGM coverage and utilization is likely to improve the health outcomes of people with diabetes. ABBREVIATIONS: A1C = glycated hemoglobin AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ASPIRE = Automation to Simulate Pancreatic Insulin Response CGM = continuous glucose monitoring HRQOL = health-related quality of life ICER = incremental cost-effectiveness ratio JDRF = Juvenile Diabetes Research Foundation MARD = mean absolute relative difference MDI = multiple daily injections QALY = quality-adjusted life years RCT = randomized, controlled trial SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR = Sensor-Augmented Pump Therapy for A1C Reduction T1D = type 1 diabetes T2D = type 2 diabetes.
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Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Endocrinología/normas , Automonitorización de la Glucosa Sanguínea/normas , Consenso , Endocrinología/organización & administración , Humanos , Calidad de VidaRESUMEN
OBJECTIVE: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group. CONCLUSIONS: Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.
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Glucemia , Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Glucemia/efectos de los fármacos , Glucemia/análisis , Adulto , Insulina/administración & dosificación , Insulina/uso terapéutico , Masculino , Femenino , Administración por Inhalación , Persona de Mediana Edad , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Periodo Posprandial , Sistemas de Infusión de Insulina , Insulina de Acción Corta/administración & dosificación , Insulina de Acción Corta/uso terapéuticoRESUMEN
BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.
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Hiperglucemia , Hipoglucemia , Adulto , Humanos , Glucemia , Automonitorización de la Glucosa Sanguínea , Hipoglucemia/diagnóstico , Hiperglucemia/diagnóstico , GlucosaRESUMEN
BACKGROUND: MYL-1601D is a proposed biosimilar of originator insulin aspart, Novolog®/NovoRapid® (Ref-InsAsp-US/Ref-InsAsp-EU). OBJECTIVE: This study assessed the immunogenicity, efficacy, and safety of MYL-1601D with Ref-InsAsp-US in patients with type 1 diabetes mellitus (T1D). METHODS: This was a 24-week, open-label, randomized, phase III study. Patients were randomized 1:1 to mealtime MYL-1601D or Ref-InsAsp-US in combination with insulin glargine (Lantus SoloSTAR®) once daily. The treatment-emergent antibody response (TEAR) rate (defined as patients who were anti-insulin antibody [AIA] negative at baseline and became positive at any timepoint post-baseline or patients who were AIA positive at baseline and demonstrated a 4-fold increase in titer values at any timepoint post-baseline) was the primary endpoint. The study also compared the change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), prandial, basal, and total daily insulin, 7-point self-monitored blood glucose (SMBG) profiles, immunogenicity, and adverse events (AEs) including hypoglycemia. RESULTS: In total, 478 patients were included in the intent-to-treat analysis (MYL-1601D: 238; Ref-InsAsp-US: 240) set. The 90% confidence interval (CI) for the primary endpoint was within the pre-defined equivalence margin of ±11.7% and the treatment differences (SE) in TEAR responders between the treatment groups was - 2.86 (4.16) with 90% CI - 9.71 to 3.99. The mean (SD) changes from baseline for HbA1c, FPG, and insulin dosages were similar in both groups at week 24. The safety profiles including hypoglycemia, immune-related events, AEs, and other reported variables were similar between the treatment groups at week 24. CONCLUSIONS: MYL-1601D demonstrated similar immunogenicity, efficacy, and safety profiles to Ref-InsAsp-US in patients with T1D over 24 weeks. CLINICAL TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03760068.
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Biosimilares Farmacéuticos , Diabetes Mellitus Tipo 1 , Hipoglucemia , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina Aspart/efectos adversos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Hipoglucemiantes/efectos adversos , Glucemia , Insulina Glargina/efectos adversos , Hipoglucemia/inducido químicamente , Insulina/efectos adversosRESUMEN
Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9-100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1-100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Biopsia con Aguja Fina , Carcinoma Neuroendocrino , Perfilación de la Expresión Génica/métodos , Humanos , ARN , Estudios Retrospectivos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/genética , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugíaRESUMEN
This is a single-center randomized open label active-controlled crossover trial comparing efficacy and safety of fast acting insulin aspart (FA) (FIASP®) versus insulin aspart (IAsp) (NovoLog®) when used in the Medtronic 670G system in auto mode in patients with type 1 diabetes. Forty patients were randomized to either IAsp or FA. Each treatment period was 7 weeks and a standardized meal test was administered 6 weeks after the start of each treatment period. The primary endpoint was postprandial glucose (PPG) increment after the meal test at 1 h. Treatment with FA using the MiniMed 670G hybrid closed loop (HCL) led to a greater reduction in 1-h postprandial glucose increase compared with treatment with IAsp during the standardized mixed meal test. Change in glucose: [estimated treatment difference (ETD ± standard deviation [SD]); 95% confidence interval]: 70.27 (±17.36) mg/dL (3.9 ± 1.0 mmol/L) with FA versus 98.42 (±17.36) mg/dL (5.5 ± 1.0 mmol/L) with IAsp (P = 0.008). Patients spent 1.81% (P = 0.016) more time (equivalent to 26 min per day) in the 70-180 mg/dL (3.89-9.99 mmol/L) range with FA than with IAsp. The entire sample spent only 0.5% of time <54 mg/dL (<3.0 mmol/L) range. The increment in the 1 h postmeal test glucose was significantly lower with FA versus IAsp. FA in a HCL setting is safe and effective with patients spending more time in the 70-180 mg/dL (3.89-9.99 mmol/L) target range than with IAsp. Trial registration: Clinicaltrials.gov identifier: NCT03977727.
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Diabetes Mellitus Tipo 1 , Insulina Aspart , Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Método Doble Ciego , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Insulina Aspart/uso terapéuticoRESUMEN
Background: The EValuating U-500R Infusion Versus Injection in Type 2 Diabetes Mellitus (VIVID) study compared two methods of U-500R insulin delivery, continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI), for 26 weeks in people with type 2 diabetes (T2D) requiring high doses of insulin. To assess glycemic variability (GV) and time in range (TIR), a subset of participants performed masked continuous glucose monitoring (CGM). Methods: VIVID participants were adults who had insulin requirements of >200 but ≤600 U/day and A1C 7.5% to 12%. Participants performed masked CGM for seven consecutive days on each of three occasions: before weeks 0 (baseline), 14, and 26. The primary objective was to compare GV between CSII and MDI groups, based on change from baseline of within-day standard deviation (SDw) of CGM glucose. Results: Of 54 participants enrolled, 41 with evaluable data were analyzed (17 and 24 in CSII and MDI groups, respectively). The CSII group had a significantly greater reduction from baseline in mean SDw of glucose (45.0 to 38.2 mg/dL [-8.1 mg/dL]) compared with the MDI group (47.0 to 45.8 [-0.4 mg/dL]; P = 0.047). TIR 70-180 mg/dL glucose increased significantly from baseline in the CSII group only, from 59.8% to 73.1% (change +12.9%, P < 0.05), but was not significantly different between groups. There were no significant between-group differences in the endpoint mean glucose or A1C. Conclusions: In the VIVID CGM substudy of U-500R in people with T2D requiring high doses of insulin, participants using CSII significantly reduced GV compared with MDI. CSII also significantly increased TIR with no difference between groups.