Comparing Video-Based, Telehealth-Delivered Exercise and Weight Loss Programs With Online Education on Outcomes of Knee Osteoarthritis : A Randomized Trial.

BACKGROUND: Scalable knee osteoarthritis programs are needed to deliver recommended education, exercise, and weight loss interventions. OBJECTIVE: To evaluate two 6-month, telehealth-delivered exercise programs, 1 with and 1 without dietary intervention. DESIGN: 3-group, parallel randomized (5:5:2) trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000930280). SETTING: Australian private health insurance members. PARTICIPANTS: 415 persons with symptomatic knee osteoarthritis and a body mass index between 28 and 40 kg/m2 who were aged 45 to 80 years. INTERVENTION: All groups received access to electronic osteoarthritis information (control). The exercise program comprised 6 physiotherapist consultations via videoconference for exercise, self-management advice, and behavioral counseling, plus exercise equipment and resources. The diet and exercise program included an additional 6 dietitian consultations for a ketogenic very-low-calorie diet (2 formulated meal replacements and a low-carbohydrate meal daily) followed by a transition to healthy eating, as well as nutrition and behavioral resources. MEASUREMENTS: Primary outcomes were changes in knee pain (numerical rating scale [NRS] of 0 to 10, higher indicating worse) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]; scale, 0 to 68, higher indicating worse) at 6 months (primary time point) and 12 months. Secondary outcomes were weight, physical activity, quality of life, mental health, global change, satisfaction, willingness to have surgery, orthopedic appointments, and knee surgery. RESULTS: A total of 379 participants (91%) provided 6-month primary outcomes, and 372 (90%) provided 12-month primary outcomes. At 6 months, both programs were superior to control for pain (between-group mean difference in change on NRS: diet and exercise, -1.5 [95% CI, -2.1 to -0.8]; exercise, -0.8 [CI, -1.5 to -0.2]) and function (between-group mean difference in change on WOMAC: diet and exercise, -9.8 [CI, -12.5 to -7.0]; exercise, -7.0 [CI, -9.7 to -4.2]). The diet and exercise program was superior to exercise (pain, -0.6 [CI, -1.1 to -0.2]; function, -2.8 [CI, -4.7 to -0.8]). Findings were similar at 12 months. LIMITATION: Participants and clinicians were unblinded. CONCLUSION: Telehealth-delivered exercise and diet programs improved pain and function in people with knee osteoarthritis and overweight or obesity. A dietary intervention conferred modest additional pain and function benefits over exercise. PRIMARY FUNDING SOURCE: Medibank, the Medibank Better Health Foundation Research Fund, and a National Health and Medical Research Council Centre of Research Excellence.

Single-center real-life experience with testosterone treatment in adult men with Prader-Willi syndrome.

Hypogonadism is the most frequent hormonal deficiency in individuals with Prader-Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide testosterone treatment in adult men with PWS. We aimed to evaluate the serum testosterone concentrations and adverse effects of testosterone treatment in individuals with PWS attending a specialist obesity management service. A retrospective audit was undertaken at Austin Health, Melbourne between January 2010 and April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and prevalence of polycythemia and behavioral disturbance. Data were available for eight individuals with median baseline age 19 years (range, 19-42) and BMI 37 kg/m2 (range, 27-71). Six men had obstructive sleep apnea; none were smokers. Baseline testosterone concentration was 1.8 nmol/L (IQR, 1.1-3.3) with hematocrit 0.43. Testosterone formulations were intramuscular testosterone undecanoate (TU) 1000 mg (n = 5), transdermal testosterone gel 50 mg daily (n = 1), and oral TU 80-120 mg daily (n = 2). Median total testosterone concentration was 9.7 nmol/L (IQR, 8.5-14.7). Nine of 25 (36%) hematocrit results in six patients measured >0.50 (range, 0.50-0.56). Intramuscular TU was well tolerated and was the only formulation to achieve serum total testosterone concentrations in the adult male reference range. Worsening behavioral disturbance resulted in treatment discontinuation in one individual. Our experience reinforces the need to regular monitoring of hematocrit in men with PWS treated with testosterone. However, a worsening of behavior problems was uncommon in this series.

Medicines for long-term obesity management.

Obesity is always genetic or epigenetic in origin in an obesogenic environment. Dietary therapy is required for weight loss. Drugs to suppress hunger and increase satiety may assist while losing weight and are essential for most patients in the weight maintenance period. A combination of drugs may be needed. A personalised approach must be used when selecting the appropriate weight loss drug for the patient. This considers possible contraindications, the method of administration and adverse effects, and includes discussing the cost of the treatment. Several drugs do not have an approved indication in Australia for weight loss.

Better Knee, Better Me™: effectiveness of two scalable health care interventions supporting self-management for knee osteoarthritis - protocol for a randomized controlled trial.

BACKGROUND: Although education, exercise, and weight loss are recommended for management of knee osteoarthritis, the additional benefits of incorporating weight loss strategies into exercise interventions have not been well investigated. The aim of this study is to compare, in a private health insurance setting, the clinical- and cost-effectiveness of a remotely-delivered, evidence- and theory-informed, behaviour change intervention targeting exercise and self-management (Exercise intervention), with the same intervention plus active weight management (Exercise plus weight management intervention), and with an information-only control group for people with knee osteoarthritis who are overweight or obese. METHODS: Three-arm, pragmatic parallel-design randomised controlled trial involving 415 people aged ≥45 and ≤ 80 years, with body mass index ≥28 kg/m2 and < 41 kg/m2 and painful knee osteoarthritis. Recruitment is Australia-wide amongst Medibank private health insurance members. All three groups receive access to a bespoke website containing information about osteoarthritis and self-management. Participants in the Exercise group also receive six consultations with a physiotherapist via videoconferencing over 6 months, including prescription of a strengthening exercise and physical activity program, advice about management, and additional educational resources. The Exercise plus weight management group receive six consultations with a dietitian via videoconferencing over 6 months, which include a very low calorie ketogenic diet with meal replacements and resources to support behaviour change, in addition to the interventions of the Exercise group. Outcomes are measured at baseline, 6 and 12 months. Primary outcomes are self-reported knee pain and physical function at 6 months. Secondary outcomes include weight, physical activity levels, quality of life, global rating of change, satisfaction with care, knee surgery and/or appointments with an orthopaedic surgeon, and willingness to undergo surgery. Additional measures include adherence, adverse events, self-efficacy, and perceived usefulness of intervention components. Cost-effectiveness of each intervention will also be assessed. DISCUSSION: This pragmatic study will determine whether a scalable remotely-delivered service combining weight management with exercise is more effective than a service with exercise alone, and with both compared to an information-only control group. Findings will inform development and implementation of future remotely-delivered services for people with knee osteoarthritis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12618000930280 (01/06/2018).

Efficacy and safety of methionine aminopeptidase 2 inhibition in type 2 diabetes: a randomised, placebo-controlled clinical trial.

AIMS/HYPOTHESIS: This multicentre randomised double-blind placebo-controlled clinical trial assessed the efficacy and safety of a methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib, in individuals with obesity (BMI ≥30 kg/m2) and type 2 diabetes (HbA1c 53-97 mmol/mol [7-11%] and fasting glucose <15.6 mmol/l). METHODS: Participants were randomised (via a centralised interactive web response system) to placebo, 1.2 or 1.8 mg beloranib s.c. twice weekly for 26 weeks. Participants, investigators and the sponsor were blinded to group assignment. The primary endpoint was the change in weight from baseline to week 26. The trial was terminated early when beloranib development was stopped because of an imbalance of venous thromboembolism events in beloranib-treated individuals vs placebo that became evident during late-stage development of the drug. RESULTS: In total, 153 participants were randomised, 51 to placebo, 52 to 1.2 mg beloranib and 50 to 1.8 mg beloranib. In participants who completed week 26, the least squares mean ± SE weight change (baseline 111 kg) was -3.1 ± 1.2% with placebo (n = 22) vs -13.5 ± 1.1% and -12.7 ± 1.3% with 1.2 and 1.8 mg beloranib, respectively (n = 25; n = 19; p < 0.0001). The change in HbA1c (baseline 67 mmol/mol [8.3%]) was -6.6 ± 2.2 mmol/mol (-0.6 ± 0.2%) with placebo vs -21.9 ± 2.2 mmol/mol (-2.0 ± 0.2%) or -21.9 ± 3.3 mmol/mol (-2.0 ± 0.3%) with 1.2 or 1.8 mg beloranib (p < 0.0001), respectively. The most common beloranib adverse events were sleep related. One beloranib-treated participant experienced a non-fatal pulmonary embolism. CONCLUSIONS/INTERPRETATION: MetAP2 inhibitors represent a novel mechanism for producing meaningful weight loss and improvement in HbA1c. TRIAL REGISTRATION: ClinicalTrials.gov NCT02324491 FUNDING: The study was funded by Zafgen, Inc.

Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes.

The prevalence of type 2 diabetes is rapidly increasing, with severe socioeconomic impacts. Excess lipid deposition in peripheral tissues impairs insulin sensitivity and glucose uptake, and has been proposed to contribute to the pathology of type 2 diabetes. However, few treatment options exist that directly target ectopic lipid accumulation. Recently it was found that vascular endothelial growth factor B (VEGF-B) controls endothelial uptake and transport of fatty acids in heart and skeletal muscle. Here we show that decreased VEGF-B signalling in rodent models of type 2 diabetes restores insulin sensitivity and improves glucose tolerance. Genetic deletion of Vegfb in diabetic db/db mice prevented ectopic lipid deposition, increased muscle glucose uptake and maintained normoglycaemia. Pharmacological inhibition of VEGF-B signalling by antibody administration to db/db mice enhanced glucose tolerance, preserved pancreatic islet architecture, improved ß-cell function and ameliorated dyslipidaemia, key elements of type 2 diabetes and the metabolic syndrome. The potential use of VEGF-B neutralization in type 2 diabetes was further elucidated in rats fed a high-fat diet, in which it normalized insulin sensitivity and increased glucose uptake in skeletal muscle and heart. Our results demonstrate that the vascular endothelium can function as an efficient barrier to excess muscle lipid uptake even under conditions of severe obesity and type 2 diabetes, and that this barrier can be maintained by inhibition of VEGF-B signalling. We propose VEGF-B antagonism as a novel pharmacological approach for type 2 diabetes, targeting the lipid-transport properties of the endothelium to improve muscle insulin sensitivity and glucose disposal.

A randomized, placebo-controlled trial of beloranib for the treatment of hypothalamic injury-associated obesity.

AIMS: Hypothalamic injury-associated obesity (HIAO) results from damage to the hypothalamus that often occurs with surgical removal/radiation therapy of tumours in the hypothalamic region, such as craniopharyngioma. There is currently no rigorously studied pharmaceutical treatment for the intractable weight gain and cardiometabolic consequences that occur in patients with HIAO. We aimed to assess efficacy, safety and tolerability of beloranib treatment for 4 to 8 weeks in patients with HIAO. MATERIALS AND METHODS: This Phase 2a, double-blind, placebo-controlled study included 14 patients with HIAO, randomized to receive beloranib 1.8 mg or placebo subcutaneously twice weekly for 4 weeks with an optional 4-week open-label extension in which all patients received beloranib. The primary endpoint was change in weight from baseline to Week 4. RESULTS: Participants were 64% female, with a mean (SD) age of 32 (9) years, BMI of 43 (7) kg/m2 and weight of 126 (22) kg. Compared with placebo (N = 4), beloranib 1.8 mg (N = 8) resulted in a mean (95% CI) difference in weight of -3.2 (-5.4, -0.9) kg after 4 weeks. Weight loss continued through the 8 weeks in patients randomized to beloranib (mean -6.2 [-8.2, -4.1] kg). Beloranib treatment was associated with improvements in high-sensitivity CRP. Adverse events were mild to moderate. No patients who received beloranib discontinued treatment. CONCLUSION: Beloranib treatment resulted in progressive weight loss in patients with HIAO that was comparable to that observed with beloranib in patients with exogenous obesity. These findings indicate a novel mechanism for treating obesity in patients with HIAO.

Obesity and weight management at menopause.

BACKGROUND: Many women report gaining weight as they transition through menopause. For most, the weight gain is modest and can be reduced with a conscious effort to limit energy intake and increase energy expenditure. However, many women who are already overweight and obese will gain more weight as they approach menopause. OBJECTIVE: The aims of this paper are to explain the reasons for menopausal weight gain and to detail a method for achieving and sustaining a substantial weight loss. DISCUSSION: Weight gain during menopause is predominantly due to a reduction in spontaneous activity. For women who are lean, advice about controlling energy intake and increasing physical activity may be all that is required to prevent weight gain. For women who are overweight and obese rapid weight loss is best achieved with the help of a very low energy diet. This must be followed by lifelong behaviour modification with or without the help of hunger-suppressing pharmacotherapy.

The interaction between physical activity and amount of baseline knee cartilage.

OBJECTIVES: Conflicting reports of the effect of physical activity on knee cartilage may be due to the heterogeneity of populations examined and, in particular, the underlying health of the knee joint. This study examined the influence of recreational and occupational physical activity on cartilage volume loss. METHODS: A total of 250 participants with no significant musculoskeletal disease were recruited. A gender-specific median cartilage volume split was used to define people in the lowest and highest 50% of baseline cartilage volume. Baseline recreational and occupational activity was examined by questionnaire, while cartilage volume was assessed by MRI at baseline and 2.4 years later. RESULTS: Significant interactions were demonstrable between physical activity and cartilage volume loss based on stratification of baseline cartilage volume (all P ⩽ 0.03). There was a dose-response relationship between frequently performed baseline occupational activities and medial cartilage volume loss in both the low (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum, 95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for interaction). Individuals with low baseline cartilage volume who were active in their occupation and/or recreational activity had greater medial cartilage volume loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P = 0.02). CONCLUSION: Whereas people with less baseline cartilage volume are more at risk of structural knee damage with either heavy occupational or recreational workloads or both, individuals with high baseline cartilage volume may advantageously modify their risk for knee OA by participating in more frequent occupational physical activities.

Weight change and change in tibial cartilage volume and symptoms in obese adults.

INTRODUCTION: There is a paucity of data examining the effects of weight change on knee joint structures and symptoms. This study examined the effect of weight change on change in knee cartilage volume and symptoms in an obese cohort. METHODS: 112 obese subjects (Body Mass Index ≥30 kg/m(2)) were recruited from various community sources to examine the effect of obesity on musculoskeletal health. Tibial cartilage volume, determined by MRI, and knee symptoms, determined by the Western Ontario and McMaster Osteoarthritis Index (WOMAC) were collected at baseline and an average of 2.3 years later. RESULTS: Percentage weight change was associated with change in medial tibial cartilage volume (ß -1.2 mm(3), 95% CI -2.3 to -0.1 mm(3), p=0.03) that was consistent throughout the spectrum of weight loss through to mild weight gain. Percentage weight change was not associated with change in the lateral tibial (p=0.93) or patella (p=0.32) cartilage volumes. Percentage weight change was associated with change in all WOMAC subscales (all p≤0.01): pain (ß -1.8 mm, 95% CI -3.2 to -0.4 mm), stiffness (ß -1.6 mm, 95% CI -2.5 to -0.7 mm) and function (ß -6.9 mm, 95% CI -11.6 to -2.1 mm). CONCLUSIONS: The linearity of effect implies that weight loss is associated with reduced medial cartilage volume loss and improved knee symptoms, while weight gain is associated with increased medial cartilage volume loss and worse knee symptoms. These results suggest that in obese people, small amounts of weight change may have the potential for a disease modifying effect on both knee joint structure and symptoms. While weight loss is an important primary management strategy in obese individuals, avoidance of further weight gain should also be a clinical goal.

Long-term persistence of hormonal adaptations to weight loss.

BACKGROUND: After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss. METHODS: We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite. RESULTS: Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001). CONCLUSIONS: One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

The longitudinal relationship between changes in body weight and changes in medial tibial cartilage, and pain among community-based adults with and without meniscal tears.

INTRODUCTION: Meniscal tears are commonly found on MRI and increase the risk for radiographic knee osteoarthritis (OA). While meniscectomy is recommended when knee pain is severe or functionally disabling, it is unclear how to best treat meniscal tears without these symptoms. The aim of this longitudinal study was to examine the effect of weight change on knee cartilage and pain in a cohort of community-based adults with and without meniscal tears detected by MRI. METHODS: 250 adults with no history of knee OA or knee injury were recruited from the general community and weight-loss clinics. MRI of the knee, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), weight and height were measured at baseline and again at follow-up approximately 2 years later. RESULTS: Medial meniscal tears were present in 36 (18%) of the cohort. In those with medial meniscal tears, after adjustment for confounders, percentage weight change was significantly associated with percentage change in medial tibial cartilage volume (ß 0.2% 95% CI 0.08% to 0.3% p=0.002) and knee pain (ß 11.6% 95% CI 2.1% to 21.1% p=0.02). That is, for every 1% gain in weight, there was an associated 0.2% increased loss of medial tibial cartilage volume and 11.6% increase in pain. In those with no medial meniscal tear, neither change in medial tibial cartilage volume (ß 0.02% 95% CI -0.01% to 0.10% p=0.53) or pain (ß 1.9% 95% CI -2.2% to 6.1% p=0.36) were significantly associated with change in weight. CONCLUSIONS: This study demonstrated that among adults with medial meniscal tears, weight gain is associated with increased cartilage loss and pain, while weight loss is associated with the converse. This suggests attention to weight is particularly important in the management of people with medial meniscal tears.

Combination phentermine and topiramate for weight maintenance: the first Australian experience.

OBJECTIVE: To investigate the safety, tolerability and efficacy of combination phentermine and topiramate therapy for maintenance of weight loss. DESIGN, SETTING AND PATIENTS: Retrospective audit of patients attending the Austin Health Weight Control Clinic who were dispensed phentermine-topiramate between 22 January 2010 and 16 July 2012 and after reaching a target weight by following a very low energy diet (VLED). Data collection continued until July 2013. MAIN OUTCOME MEASURES: Number of patients who ceased pharmacotherapy; duration of use of pharmacotherapy; types and numbers of adverse effects; and mean weight and blood pressure measurements at the initial visit, the end of the VLED and the last observation during pharmacotherapy. RESULTS: Data were available for 103 patients who were dispensed phentermine-topiramate; 61 patients ceased combination pharmacotherapy before the end of the data collection period, 41 due to adverse effects (eg, paraesthesia, cognitive changes, dry mouth and depression). The mean duration of use of pharmacotherapy was 10 months. Mean weight decreased by 10% due to the VLED (from 135.5 kg to 122.5 kg) and this loss was maintained. For 30 patients who continued on phentermine-topiramate, the mean duration of pharmacotherapy was 22 months and the mean weight decreased by 6.7 kg between the end of the VLED and the last observation during pharmacotherapy. CONCLUSION: Phentermine-topiramate therapy was not well tolerated; more than half of the patients in our study stopped taking it because of adverse effects, and more than half of the adverse events reported were ascribed to topiramate. However, in those able to continue with pharmacotherapy, the combination was efficacious for both maintenance of weight loss and ongoing weight loss.

GPR119 agonists for type 2 diabetes: past failures and future hopes for preclinical and early phase candidates.

INTRODUCTION: Type 2 diabetes (T2D) is metabolic disorder associated with a decrease in insulin activity and/or secretion from the ß-cells of the pancreas, leading to elevated circulating glucose. Current management practices for T2D are complex with varying long-term effectiveness. Agonism of the G protein-coupled receptor GPR119 has received a lot of recent interest as a potential T2D therapeutic. AREAS COVERED: This article reviews studies focused on GPR119 agonism in animal models of T2D and in patients with T2D. EXPERT OPINION: GPR119 agonists in vitro and in vivo can potentially regulate incretin hormone release from the gut, then pancreatic insulin release which regulates blood glucose concentrations. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity, failed to translate to early-stage clinical trials in patients with T2D. However, in more recent studies, acute and chronic dosing with the GPR119 agonist DS-8500a had increased efficacy, although this compound was discontinued for further development. New trials on GPR119 agonists are needed, however it may be that the future of GPR119 agonists lie in the development of combination therapy with other T2D therapeutics.

The defence of body weight: a physiological basis for weight regain after weight loss.

Although weight loss can usually be achieved by restricting food intake, the majority of dieters regain weight over the long-term. In the hypothalamus, hormonal signals from the gastrointestinal tract, adipose tissue and other peripheral sites are integrated to influence appetite and energy expenditure. Diet-induced weight loss is accompanied by several physiological changes which encourage weight regain, including alterations in energy expenditure, substrate metabolism and hormone pathways involved in appetite regulation, many of which persist beyond the initial weight loss period. Safe effective long-term strategies to overcome these physiological changes are needed to help facilitate maintenance of weight loss. The present review, which focuses on data from human studies, begins with an outline of body weight regulation to provide the context for the subsequent discussion of short- and long-term physiological changes which accompany diet-induced weight loss.

Our biology working against us in obesity: A narrative review on implications for management of osteoarthritis.

Obesity is the major modifiable risk factor for osteoarthritis (OA). A major focus of management in OA is weight loss. Although we live in an obesogenic environment, obesity has a predominantly genetic and epigenetic basis. This explains a person's weight set point which is defended by biological mechanisms making weight loss difficult to achieve and maintain long term, regardless of the methods used. Significant weight regain occurs after weight loss, with weight tending to return to pre-treatment levels after cessation of interventions including the glucagon-like peptide-1 (GLP-1) agonists. An area that has received little attention is the slow, insidious weight creep of 0.5-1 kg/year over adulthood that sees individuals relentlessly increase weight. There is evidence that low intensity, personalised lifestyle interventions can prevent this weight creep, providing patients with achievable goals. In this narrative review, we examine the evidence for weight loss in OA, the biological mechanisms that make weight loss difficult to achieve and maintain and the potential negative impacts on patients. We review the evidence for preventing weight gain, the improvement in patient outcomes and the potential for significant healthcare savings through reduced knee replacements. We propose a combined approach of weight loss when indicated, together with targeting weight creep across adult years and the potential role of metformin. Implementing these combined approaches is likely to be more effective in improving patient related outcomes, reducing joint damage and healthcare costs, than our current focus on achieving weight loss in OA.

Intensive management of obesity in people with Prader-Willi syndrome.

PURPOSE: Prader-Willi syndrome (PWS) is characterised by childhood-onset hyperphagia and obesity however limited data are available to guide treatment of obesity in this population. We aimed to evaluate the safety, tolerability, and efficacy of intensive medical weight loss interventions (very-low-energy diets [VLED] and/or pharmacotherapy) in individuals with PWS attending a specialist obesity management service. METHODS: A retrospective audit was undertaken of individuals with PWS attending the Austin Health Weight Control Clinic between January 2010-April 2021. Main outcome measures were weight outcomes, duration of use, and adverse effects. RESULTS: Data were available for 18 patients, of whom 15 were treated with intensive weight loss interventions. Median (interquartile range, IQR) age at baseline was 20 years (19-32) with median body weight 90 kg (75-118) and BMI 37 kg/m2 (30-51). Median weight loss during VLED (n = 7) was 14 kg (1-20 kg) over 60 weeks. Median weight loss with phentermine-topiramate (n = 7) was 17 kg (IQR 9-19 kg) over 56 weeks. Median weight loss with liraglutide 0.6-3 mg (n = 7), prescribed with topiramate in 3 individuals, was 9 kg (2-14 kg) over 96 weeks. Naltrexone-bupropion resulted in weight loss in 2 of 4 individuals. Thirteen individuals achieved ≥10% weight loss but only 5 individuals maintained ≥10% weight loss at last follow-up. Five individuals discontinued pharmacotherapy due to adverse effects. CONCLUSIONS: VLED and pharmacotherapy can achieve substantial weight loss in some individuals with PWS though non-adherence results in substantial weight regain. Adverse effects were ascribed to phentermine and topiramate, whereas liraglutide was well-tolerated in this population.

Impact of starting BMI and degree of weight loss on changes in appetite-regulating hormones during diet-induced weight loss.

OBJECTIVE: The aim of this study was to determine whether the hormone changes following weight loss are proportional to the degree of weight loss and to starting BMI. METHODS: A very low-energy diet was used to achieve 15% weight loss. Fasting and postprandial gut hormones and leptin were measured during a meal test at baseline and at 5% (1%), 10% (2%), and 15% (2.5%) weight loss. Linear mixed-effects models were used to analyze hormone changes. RESULTS: From baseline to 5% weight loss, decreases were seen in fasting concentrations of leptin (-8.25 ng/mL; p < 0.001), amylin (-21.3 pg/mL; p < 0.001), and glucagon-like peptide 1 (-59.55 pg/mL; p < 0.001). There was a small further reduction in leptin between 5% and 15% weight loss (-1.88 ng/mL; p = 0.019) but not in glucagon-like peptide 1 and amylin. Fasting ghrelin showed a significant increase at 10% weight loss (41.64 pg/mL; p = 0.002), with a nonsignificant increase from 10% to 15% loss (26.03 pg/mL; p = 0.065). Postprandial changes in hormone levels were variable. There was no correlation between baseline weight and the degree of hormone changes. CONCLUSIONS: The majority of changes in fasting gut hormones and leptin occurred in early weight loss, with minor further changes up to 15% weight loss. Starting weight did not affect the degree of hormone change.

The Australian Obesity Management Algorithm: A simple tool to guide the management of obesity in primary care.

Obesity is a complex and multifactorial chronic disease with genetic, environmental, physiological and behavioural determinants that requires long-term care. Obesity is associated with a broad range of complications including type 2 diabetes, cardiovascular disease, dyslipidaemia, metabolic associated fatty liver disease, reproductive hormonal abnormalities, sleep apnoea, depression, osteoarthritis and certain cancers. An algorithm has been developed (with PubMed and Medline searched for all relevant articles from 1 Jan 2000-1 Oct 2021) to (i) assist primary care physicians in treatment decisions for non-pregnant adults with obesity, and (ii) provide a practical clinical tool to guide the implementation of existing guidelines (summarised in Appendix 1) for the treatment of obesity in the Australian primary care setting. MAIN RECOMMENDATIONS AND CHANGES IN MANAGEMENT: Treatment pathways should be determined by a person's anthropometry (body mass index (BMI) and waist circumference (WC)) and the presence and severity of obesity-related complications. A target of 10-15% weight loss is recommended for people with BMI 30-40 kg/m2 or abdominal obesity (WC > 88 cm in females, WC > 102 cm in males) without complications. The treatment focus should be supervised lifestyle interventions that may include a reduced or low energy diet, very low energy diet (VLED) or pharmacotherapy. For people with BMI 30-40 kg/m2 or abdominal obesity and complications, or those with BMI > 40 kg/m2 a weight loss target of 10-15% body weight is recommended, and management should include intensive interventions such as VLED, pharmacotherapy or bariatric surgery, which may be required in combination. A weight loss target of > 15% is recommended for those with BMI > 40 kg/m2 and complications and they should be referred to specialist care. Their treatment should include a VLED with or without pharmacotherapy and bariatric surgery.