The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery—a Retrospective Analysis

Purpose

About 20–25% of patients experience weight regain (WR) or insufficient weight loss (IWL) after bariatric metabolic surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with the GLP-1 receptor agonist semaglutide in non-diabetic patients with WR or IWL after BS.

Materials and Methods

Post-bariatric patients without type 2 diabetes (T2D) with WR or IWL (n?=?44) were included in the analysis. The primary endpoint was weight loss 3 and 6 months after initiation of adjunct treatment. Secondary endpoints included change in BMI, HbA1c, lipid profile, hs-CRP, and liver enzymes.

Results

Patients started semaglutide 64.7?±?47.6 months (mean?±?SD) after BS. At initiation of semaglutide, WR after post-bariatric weight nadir was 12.3?±?14.4% (mean?±?SD). Total weight loss during semaglutide treatment was???6.0?±?4.3% (mean?±?SD, p?<?0.001) after 3 months (3.2 months, IQR 3.0–3.5, n?=?38) and???10.3?±?5.5% (mean?±?SD, p?<?0.001) after 6 months (5.8 months, IQR 5.8–6.4, n?=?20). At 3 months, categorical weight loss was?>?5% in 61% of patients,?>?10% in 16% of patients, and?>?15% in 2% of patients. Triglycerides (OR?=?0.99; p?<?0.05), ALT (OR?=?0.87; p?=?0.05), and AST (OR?=?0.89; p?<?0.05) at baseline were negatively associated with weight loss of at least 5% at 3 months’ follow-up (p?<?0.05).

Conclusion

Treatment options to manage post-bariatric excess weight (regain) are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post-bariatric patients. However, these results need to be confirmed in a prospective randomized controlled trial to close the gap between lifestyle intervention and revision surgery in patients with IWL or WR after BS.

Graphical abstract

     

Using online content uniformity measurements for rapid automated process development exemplified via an X-ray system

This paper addresses the relevance of automated content testing for the rapid automated process development (RAPD). Our previous work demonstrated that RAPD allowed a fast and efficient development of a continuous capsule-filling process. Target was the mean weight and the relative standard deviation of the weight. Likewise important are the content and the content uniformity. However, an implementation demands a certain level of automation. In general, technology is available that can detect active pharmaceutical ingredient (API) inside the capsules but the final application is linked to additional development and investment in machinery. To eliminate doubts regarding the benefits of an automated content check within the RAPD we present an application example. First, an X-ray system was used to detect barium sulfate accurately inside capsules. Second, a process was developed where barium sulfate was filled. The concentration of excipients was modified in the experiments, as well as the setting of the process parameter. The obtained model provided an explicit understanding of the process. Subsequently, the content uniformity model was compared to a model of the capsule weight relative standard deviation, confirming the benefits of an automated content check in the RAPD. Moreover, we presented another example illustrating the advantages of a connected continuous filling process, which permits evaluation of all process steps and their interactions (i.e. evaluation of the entire process).     

HPTN 068: A Randomized Control Trial of a Conditional Cash Transfer to Reduce HIV Infection in Young Women in South Africa—Study Design and Baseline Results

Young women in South Africa are at high risk for HIV infection. Cash transfers offer promise to reduce HIV risk. We present the design and baseline results from HPTN 068, a phase III, individually randomized trial to assess the effect of a conditional cash transfer on HIV acquisition among South African young women. A total of 2533 young women were randomized to receive a monthly cash transfer conditional on school attendance or to a control group. A number of individual-, partner-, household- and school-level factors were associated with HIV and HSV-2 infection. After adjusting for age, all levels were associated with an increased odds of HIV infection with partner-level factors conveying the strongest association (aOR 3.05 95 % CI 1.84–5.06). Interventions like cash transfers that address structural factors such as schooling and poverty have the potential to reduce HIV risk in young women in South Africa.     

Clinical and Multimodal Imaging Findings and Risk Factors for Ocular Involvement in a Presumed Waterborne Toxoplasmosis Outbreak,Brazil

In 2015, an outbreak of presumed waterborne toxoplasmosis occurred in Gouveia, Brazil. We conducted a 3-year prospective study on a cohort of 52 patients from this outbreak, collected clinical and multimodal imaging findings, and determined risk factors for ocular involvement. At baseline examination, 12 (23%) patients had retinochoroiditis; 4 patients had bilateral and 2 had macular lesions. Multimodal imaging revealed 2 distinct retinochoroiditis patterns: necrotizing focal retinochoroiditis and punctate retinochoroiditis. Older age, worse visual acuity, self-reported recent reduction of visual acuity, and presence of floaters were associated with retinochoroiditis. Among patients, persons >40 years of age had 5 times the risk for ocular involvement. Five patients had recurrences during follow-up, a rate of 22% per person-year. Recurrences were associated with binocular involvement. Two patients had late ocular involvement that occurred >34 months after initial diagnosis. Patients with acquired toxoplasmosis should have long-term ophthalmic follow-up, regardless of initial ocular involvement.     

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice

Previous studies proposed the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a receptor expressed in myeloid cells including microglia in brain and osteoclasts in bone, as a link between brain and bone disease. The TREM2 R47H variant is a known risk factor for Alzheimer's disease (AD), the most common form of dementia. To investigate whether altered TREM2 signaling could contribute to bone and skeletal muscle loss, independently of central nervous system defects, we used mice globally hemizygous for the TREM2 R47H variant (TREM2^R47H/+), which do not exhibit AD pathology, and wild-type (WT) littermate control mice. Dxa/Piximus showed bone loss in female TREM2^R47H/+ animals between 4 and 13 months of age and reduced cancellous and cortical bone (measured by micro-computed tomography [μCT]) at 13 months, which stalled out by 20 months of age. In addition, they exhibited decreased femoral biomechanical properties measured by three-point bending at 13 months of age, but not at 4 or 20 months. Male TREM2^R47H/+ animals had decreased trabecular bone geometry but increased ultimate strain and failure force at 20 months of age versus WT. Only male TREM2^R47H/+ osteoclasts differentiated more ex vivo after 7 days with receptor activator of nuclear factor κB ligand (RANKL)/macrophage colony-stimulating factor (M-CSF) compared to WT littermates. Yet, estrogen receptor alpha expression was higher in female and male TREM2^R47H/+ osteoclasts compared to WT mice. However, female TREM2^R47H/+ osteoclasts expressed less complement 3 (C3), an estrogen responsive element, and increased protein kinase B (Akt) activity, suggesting altered estrogen signaling in TREM2^R47H/+ cells. Despite lower bone volume/strength in TREM2^R47H/+ mice, skeletal muscle function measured by plantar flexion and muscle contractility was increased in 13-month-old female mutant mice. Overall, these data demonstrate that an AD-associated TREM2 variant can alter bone and skeletal muscle strength in a sex-dimorphic manner independent of central neuropathology, potentially mediated through changes in osteoclastic intracellular signaling. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).