Background: Patients with underlying medical conditions have a greater risk of developing severe COVID-19. Unlike vaccine-derived immunity which develops over time, administration of neutralizing monoclonal antibodies is an immediate, passive humoral immunotherapy, with the potential to reduce disease progression, emergency room visits, hospitalizations, and death. Methods: In this phase 3 portion of the BLAZE-1 trial, a high-risk ambulatory cohort of 1035 patients with mild-to-moderate COVID-19 were randomly assigned 1:1 to receive a single intravenous infusion of a neutralizing monoclonal antibody combination treatment consisting of 2800mg bamlanivimab+2800mg etesevimab together, or placebo, within 3 days of laboratory diagnosis. The primary outcome was overall patient clinical status, measured by the proportion of patients who experienced COVID-19-related hospitalization or death by any cause by Day 29. Results: 1035 patients were randomized and infused (mean age [SD];53.8 years [16.8], female (52%)). A 70% reduction in COVID-19-related hospitalization and death by any cause by Day 29 was observed in patients who received the bamlanivimab+etesevimab combination treatment (11/518 arm total) compared to those who received placebo (36/517 arm total) (Δ[95% CI]=-4.8[-7.4,-2.3])(p=0.0004). No deaths were observed among patients who received the combination treatment, 10 deaths were reported in the placebo group, at least 8 designated COVID-19-related. A significantly greater reduction in log10(viral load) from baseline at Day 7 was observed amongst patients who received bamlanivimab+etesevimab compared to placebo (Δ[95% CI]=-1.20[-1.46,-0.94])(p<0.00000001). The median time to sustained symptom resolution was shorter for those who received the combination treatment (days [95% CI]=8[7.0,8.0]) compared to those who received placebo (days [95% CI]=9[8.0,10.0])(p=0.007). Similar rates of adverse events were observed between placebo (60/517,11.6%) and combination treatment groups (69/518,13.3%). Conclusion: 2800mg bamlanivimab+2800mg etesevimab neutralizing monoclonal antibody combination therapy significantly reduced COVID-19- related hospitalizations and deaths amongst high-risk ambulatory patients and accelerated the decline in viral load and disease symptoms over time. This study confirms that early intervention with bamlanivimab + etesevimab greatly improves the clinical outcomes for high-risk ambulatory patients, and links reduction in nasopharyngeal viral load to clinically meaningful benefits.

Aim: Real-world effectiveness of insulin therapy is affected by poor treatment persistence, often occurring soon after initiation. An international cross-sectional survey of people with type 2 diabetes mellitus (T2DM) has been conducted to describe reasons for non-persistence with insulin therapy. Methods: Responders to an online survey in 7 countries were classified as continuers (no gap of >= 7 days), interrupters (interrupted therapy for >= 7 days within first 6 months, then restarted), and discontinuers (terminated therapy for >= 7 days within first 6 months, no restart before survey). We present the results from the United Kingdom (UK) cohort. Results; Of 942 global respondents, 131 were from the UK, having a mean age of 37 years and a mean of 7 years since first T2DM diagnosis. Reasons contributing to insulin continuation (n = 50) were improved physical feeling (52.0%) and improved glycemic control (48.0%). Common reasons for interruption (n = 50) or discontinuation (n = 31), respectively were weight gain (50.0%, 48.4%) and hypoglycemia (38.0%, 25.8%). Most important reason for possible re-initiation for interrupters and discontinuers, respectively was persuasion by physician/healthcare professional (74.0%, 64.5%). Conclusion: The benefits of basal insulin therapy motivated continuers to persist with the treatment; experienced or anticipated side effects contributed to interruption and discontinuation. (C) 2018 Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe.

To evaluate the effects of once weekly dulaglutide 1.5 mg versus insulin glargine or exenatide BID on HbA1c, weight and hypoglycaemia in the AWARD-1 and AWARD-2 clinical trials with patients with baseline HbA1c ≥7.5%.

AIM:To describe the characteristics and management of patients with diabetes who chose to fast during Ramadan in 2010.METHODS:This was a multi-country, retrospective, observational study, supplemented with physician and patient questionnaires, with data captured before, during and after Ramadan. A total of 508 physicians in 13 countries enrolled 3777 patients and a total of 3394 evaluable cases were analysed. We report on the subset of patients with Type 2 diabetes, which included 3250 patients (95.8%).RESULTS:Oral anti-hyperglycaemic therapy was the predominant pre-Ramadan therapy for most patients (76.6%). The treatment regimen was modified before Ramadan for 39.3% of all patients (34.9% for patients on oral drugs alone, 47.1% for patients on injectable drugs alone). Almost all physicians (96.2%) reported providing fasting-specific advice to patients and 62.6% report using guidelines or recommendations for the management of diabetes during Ramadan. In all, 64% of patients reported fasting everyday of Ramadan and 94.2% fasted for at least 15 days.CONCLUSIONS:Physicians have increasingly adopted multiple approaches to the management of fasting during Ramadan, including the adoption of international and/or national guidelines, providing fasting-specific advice and adjusting treatment regimens, such that patients are able to fast for a greater number of days without acute complications. Additional research is needed to explore physician and patient beliefs and practices to inform the evidence-based management of diabetes while fasting, both during and outside of Ramadan, and to identify and address barriers to the universal uptake of techniques to facilitate that management.

Introduction: We estimated the percentage of patients with baseline HbA1c ≥7.5% achieving HbA1c reduction ≥1% and weight loss ≥3% [NICE continuity criteria for glucagon-like peptide-1 (GLP-1) receptor agonists] after 26 weeks treatment with dulaglutide or exenatide, combined with oral antidiabetes medications.

Aim: To investigate the response to long- and short-acting glucagon-like peptide-1 receptor agonists based on baseline HbA1c levels. The AWARD-1 trial compared once weekly dulaglutide 1.5 mg and dulaglutide 0.75 mg to placebo and exenatide 10 µg bid in patients with T2DM on metformin and pioglitazone.

Évaluer la réponse aux agonistes des récepteurs du glucagon-like peptide-1 à action prolongée ou rapide en fonction du taux initial d'HbA1c. L'essai AWARD-1 a comparé le dulaglutide 1,5 mg et 0,75 mg hebdomadaire au placebo, à l'exénatide 10 μg 2 fois par jour chez des DT2 sous metformine et pioglitazone. Les variations d'HbA1c à partir du taux initial et le pourcentage de patients atteignant les valeurs cibles d'HbA1c (< 7 % et < 6,5 %) avec dulaglutide 1,5 mg et 0,75 mg à 26 semaines ont été analysées en fonction du taux initial d'HbA1c (< 8,5 %, ≥ 8,5%) et comparées au placebo et à l'exénatide. Les résultats sont présentés (moyenne des moindres carrés [MMC] ± erreur-type) pour les variations d'HbA1c à partir du taux initial et les pourcentages atteignant les cibles glycémiques, pour le groupe < 8,5 % suivi du groupe ≥ 8,5 %. Les variations d'HbA1c (MMC) à partir du taux initial sous dulaglutide 1,5 (– 1,16[0,07]%; –2,37[0,10]%) étaient supérieures versus placebo (0,17 [0,10] % ; –0,76 [0,16] %] et exénatide (− 0,64[0, 07]%; –1,86[0,11] %) (p < 0,001, toute comparaison). Avec dulaglutide 1,5 mg un nombre significativement supérieur de patients dans les deux groupes (HbA1c initiale < 8,5 % et ≥ 8,5 %), a atteint les cibles < 7 % (92 %, 47 %) et ≤ 6,5 % (80 %, 26 %) versus placebo (< 7 %: 55 %, 10 %; ≤6,5 %: 32 %, 3 %) et exénatide (< 7 %: 65 %, 21 %; ≤6,5%: 50%, 9%) (p < 0,05, toute comparaison). Dulaglutide 0,75 mg a aussi démontré des variations significatives pour les deux groupes initiaux versus placebo (p < 0,05 pour les deux cibles, toute comparaison). La signification statistique n'a pas été atteinte pour la comparaison dulaglutide 0,75 mg versus exénatide dans les groupes avec une HbA1c initiale ≥ 8,5 %. Quel que soit le taux initial d'HbA1c, l'administration hebdomadaire de dulaglutide 1,5 mg et 0,75 mg a montré une réduction importante d'HbA1c dans cette population de patients atteints de DT2.

Aim: To compare once weekly dulaglutide 1.5 mg and dulaglutide 0.75 mg with placebo at 26 weeks, and with sitagliptin 100 mg once daily (AWARD-5) and exenatide 10 µg twice daily (AWARD-1) at 26 and 52 weeks in patients with Type 2 diabetes with a mean baseline HbA1c of approximately 8%.

Comparer les doses hebdomadaires de dulaglutide 1,5 mg et 0,75 mg au placebo à 26 semaines, exénatide 10 μg 2 fois par jour (AWARD-1) et à sitagliptine 100 mg/jour (AWARD-5) à 26 et 52 semaines chez des patients atteints de diabète de type 2 ayant un taux initial d'HbA1c moyen d'environ 8 %. Les données des bras dulaglutide 1,5 mg, dulaglutide 0,75 mg et placebo ont été poolées par traitement. Des comparaisons des variations d'HbA1c (moyenne des moindres carrés [MMC] ± erreur-type) et du pourcentage de patients atteignant les valeurs cibles d'HbA1c < 7 % et < 6,5 %, à 26 semaines et 52 semaines, ont été réalisées. À 26 semaines, dulaglutide 1,5 mg et 0,75 mg ont présenté respectivement des réductions d'HbA1c de – 1,34 (0,05) % et de – 1,12 (0,05) %, significativement supérieures à celles de l'exénatide (– 0,80 [0,06] %), sitagliptine (– 0,74 [0,06] %) et placebo (– 0,15 [0,06] %) (p < 0,001, toute comparaison). Un nombre supérieur de patients avait atteint une HbA1c < 7 % avec dulaglutide (1,5 mg : 69 % ; 0,75 mg : 60 %) comparé à exénatide (52 %), sitagliptine (38 %) et placebo (30 %) (p < 0,001, toute comparaison). Des résultats similaires ont été démontrés avec les deux doses de dulaglutide pour la cible < 6,5 % comparés à exénatide, sitagliptine et placebo (p < 0,001, toute comparaison). À 52 semaines, dulaglutide 1,5 mg et 0,75 mg ont montré une variation supérieure d'HbA1c par rapport au taux initial, comparé à exénatide et sitagliptine, avec plus de patients atteignant une HbA1c < 7 % et < 6,5 % (p < 0,001, toute comparaison). Comparé aux autres traitements de la voie des incrétines habituellement utilisés, le dulaglutide hebdomadaire a présenté une efficacité supérieure jusqu'à 52 semaines. Ces réductions importantes d'HbA1c ont été observées malgré un taux initial moyen d'HbA1c relativement bas.