Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial

Background: Semaglutide is an effective treatment for type 2 diabetes; however, 20–30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. Methods: We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (≥18 years) with inadequately controlled type 2 diabetes (HbA1c 8·0–10·0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2·0 mg or 1·0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA1c (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162. Findings: Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58·0 years [SD 10·0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2·0 mg (n=480 [50%]) or 1·0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2·0 mg group and 471 (98%) in the semaglutide 1·0 mg group completed the trial. Mean baseline HbA1c was 8·9% (SD 0·6; 73·3 mmol/mol [SD 6·9]) and BMI was 34·6 kg/m2 (SD 7·0). Mean change in HbA1c from baseline at week 40 was −2·2 percentage points with semaglutide 2·0 mg and −1·9 percentage points with semaglutide 1·0 mg (estimated treatment difference [ETD] −0·23 percentage points [95% CI −0·36 to −0·11]; p=0·0003; trial product estimand) and −2·1 percentage points with semaglutide 2·0 mg and −1·9 percentage points with semaglutide 1·0 mg (ETD −0·18 percentage points [–0·31 to −0·04]; p=0·0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was −6·9 kg with semaglutide 2·0 mg and −6·0 kg with semaglutide 1·0 mg (ETD −0·93 kg [95% CI −1·68 to −0·18]; p=0·015; trial product estimand) and −6·4 kg with semaglutide 2·0 mg and −5·6 kg with semaglutide 1·0 mg (ETD −0·77 kg [–1·55 to 0·01]; p=0·054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2·0 mg group and 148 [31%] in the 1·0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2·0 mg and 25 (5%) participants given semaglutide 1·0 mg. Three deaths were reported during the trial (one in the semaglutide 1·0 mg group and two in the semaglutide 2·0 mg group). Interpretation: Semaglutide 2·0 mg was superior to 1·0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control. Funding: Novo Nordisk

The Soft X-ray Imager (SXI) on the SMILE Mission

The Soft X-ray Imager (SXI) is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission. SMILE is a joint science mission between the European Space Agency (ESA) and the Chinese Academy of Sciences (CAS) and is due for launch in 2025. SXI is a compact X-ray telescope with a wide field-of-view (FOV) capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit. SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange (SWCX) process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere. SWCX provides a mechanism for boundary detection within the magnetosphere, such as the position of Earth’s magnetopause, because the solar wind heavy ions have a very low density in regions of closed magnetic field lines. The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours. SXI is led by the University of Leicester in the United Kingdom (UK) with collaborating organisations on hardware, software and science support within the UK, Europe, China and the United States

What should selective cardiometabolic prevention programmes in European primary care look like? A consensus-based design by the SPIMEU group.

Background Selective prevention of cardiometabolic diseases (CMD)-that is, preventive measures specifically targeting the high-risk population-may represent the most effective approach for mitigating rising CMD rates. Objectives To develop a universal concept of selective CMD prevention that can guide implementation within European primary care. Methods Initially, 32 statements covering different aspects of selective CMD prevention programmes were identified based on a synthesis of evidence from two systematic literature reviews and surveys conducted within the SPIMEU project. The Rand/UCLA appropriateness method (RAM) was used to find consensus on these statements among an international panel consisting of 14 experts. Before the consensus meeting, statements were rated by the experts in a first round. In the next step, during a face-to-face meeting, experts were provided with the results of the first rating and were then invited to discuss and rescore the statements in a second round. Results In the outcome of the RAM procedure, 28 of 31 statements were considered appropriate and three were rated uncertain. The panel deleted one statement. Selective CMD prevention was considered an effective approach for preventing CMD and a proactive approach was regarded as more effective compared to case-finding alone. The most efficient method to implement selective CMD prevention systematically in primary care relies on a stepwise approach: initial risk assessment followed by interventions if indicated. Conclusion The final set of statements represents the key characteristics of selective CMD prevention and can serve as a guide for implementing selective prevention actions in European primary care

Adverse Pregnancy Outcomes and Incident Heart Failure in the Women's Health Initiative

Importance: Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. Objective: To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI). Design, Setting, and Participants: In 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021. Exposures: APOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery). Main Outcomes and Measures: All confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods. Results: Of 10292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF. Conclusions and Relevance: In this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF.. © 2021 American Medical Association. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]