Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial.

Background: Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination.

Methods: In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18-55 years with a body-mass index 27·0-39·9 kg/m and who were otherwise healthy were recruited from a single centre in the USA.

Effect of 6 weeks of very low-volume high-intensity interval training on oral glucose-stimulated incretin hormone response.

Decreased fasting and oral glucose-stimulated incretin hormone concentrations following moderate-intensity continuous endurance training interventions have been reported in glucose-tolerant people, however results are conflicting. The effect of more time-efficient, very low-volume, high-intensity interval training (HIT) on circulating incretin hormone levels has never been studied. Ten sedentary and overweight-to-obese participants (4 women and 6 men; age 43 ± 6 years (mean ± SD); BMI 30.

Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial.

Objective: Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg.

Macrophage Area Content and Phenotype in Hepatic and Adipose Tissue in Patients with Obesity Undergoing Roux-en-Y Gastric Bypass.

Objective: To investigate hepatic and adipose tissue macrophage content in subjects with obesity and the role of adipose tissue macrophages in weight loss-induced improved insulin sensitivity (IS).

Methods: A cross-sectional and a longitudinal study were combined to investigate the role of macrophages in subcutaneous (SAT) and visceral (VAT) adipose tissue and the liver in obesity-induced impaired IS and improvements with weight loss. Macrophage markers (CD68, CD163, and CD206) in SAT, VAT, and the liver from patients with obesity were investigated.

The Effect of Preoperative Type 2 Diabetes and Physical Fitness on Mental Health and Health-Related Quality of Life after Roux-en-Y Gastric Bypass.

Objective. To investigate the predictive value of type 2 diabetes and lack of physical activity for mental health and health-related quality of life after Roux-en-Y gastric bypass. Method.

Hepatic mitochondrial oxidative phosphorylation is normal in obese patients with and without type 2 diabetes.

Key Points: Hepatic insulin resistance in patients with obesity or type 2 diabetes has been suggested to result from hepatic mitochondrial dysfunction. High-resolution respirometry (HRR) can be used to assess oxidative phosphorylation by measuring the mitochondrial oxygen consumption rate in the individual complexes of the mitochondria. By using HRR, the present study demonstrates no difference in hepatic mitochondrial oxidative phosphorylation among subjects with obesity with or without type 2 diabetes and non-obese controls.

The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes.

Aims: The impact of diet-induced weight loss and weight loss due to RYGB in patients with (T2DM, N = 16) and without (OB, N = 27) type 2 diabetes was studied.

Methods: At inclusion (A), after diet-induced weight loss (B), 4 months post-surgery (C) and 18 months post-surgery (D) body composition, hepatic glucose production (HGP), insulin-mediated glucose uptake (GIR), respiratory exchange ratio, hepatic insulin sensitivity and clearance were determined. GLUT4, intramuscular triglycerides (IMTG) and glycogen content were measured in skeletal muscle.

Adipose tissue mitochondrial respiration and lipolysis before and after a weight loss by diet and RYGB.

Objective: To study adipose tissue mitochondrial respiration and lipolysis following a massive weight loss.

Methods: High resolution respirometry of adipose tissue biopsies and tracer determined whole body lipolysis. Sixteen obese patients with type 2 diabetes (T2DM) and 27 without (OB) were studied following a massive weight loss by diet and Roux-en-Y gastric bypass (RYGB).

A novel method for determining human ex vivo submaximal skeletal muscle mitochondrial function.

The present study utilized a novel method aiming to investigate mitochondrial function in human skeletal muscle at submaximal levels and at a predefined membrane potential. The effect of age and training status was investigated using a cross-sectional design. Ageing was found to be related to decreased leak regardless of training status.

Preoperative β-cell function in patients with type 2 diabetes is important for the outcome of Roux-en-Y gastric bypass surgery.

The majority of the patients with type 2 diabetes (T2DM) show remission after Roux-en-Y gastric bypass (RYGB). This is the result of increased postoperative insulin sensitivity and β-cell secretion. The aim of the present study was to elucidate the importance of the preoperative β-cell function in T2DM for the chance of remission after RYGB.

The psychological profile of bariatric patients with and without type 2 diabetes: baseline results of the longitudinal GASMITO-PSYC study.

Background: Some bariatric patients are referred for surgery with a diagnosis of type 2 diabetes while others are referred without co-morbid diabetes, but psychological differences between patients with and without type 2 diabetes undergoing bariatric surgery have not yet been investigated. The objective of this study was to present the baseline results of the longitudinal GASMITO-PSYC study, and to evaluate the psychological differences between bariatric patients with and without type 2 diabetes.

Methods: A total of 129 Roux-en- Y gastric bypass patients were recruited from the bariatric clinic at a hospital in the suburban Copenhagen area.

Meal induced gut hormone secretion is altered in aerobically trained compared to sedentary young healthy males.

Postprandial insulin release is lower in healthy aerobically trained (T) compared to untrained (UT) individuals. This may be mediated by a lower release of the two incretin hormones [glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] in T. The aim of this study was to assess and compare gut hormone response and satiety changes after a liquid meal intake in young, healthy T and UT males.

Immobilization increases interleukin-6, but not tumour necrosis factor-α, release from the leg during exercise in humans.

Data on interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL-6 and TNF-α release during exercise. We have now studied the temporal relationship of leg IL-6 and TNF-α release before and during isolated two-legged exercise after 14 days of one-leg immobilization (IM) while the other leg served as the control (CON) leg.

Quantitative vertebral morphometry using neighbor-conditional shape models.

A novel method for vertebral fracture quantification from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely normal vertebra shapes are estimated conditional on the shapes of all other vertebrae in the image. The difference between the true shape and the reconstructed normal shape is subsequently used as a measure of abnormality.

Quantitative vertebral morphometry using neighbor-conditional shape models.

A novel method for vertebral fracture quantification from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely normal vertebra shapes are estimated conditional on all other vertebrae in the image. The differences between the true shape and the reconstructed normal shape is subsequently used as a measure of abnormality.