Time to unshackle the medical treatment of obesity in the NHS.

Obesity affects one in four people in the United Kingdom and costs the National Health Service (NHS) ∼£6.5 billion annually. The glucagon-like peptide-1 (GLP-1) receptor analogues, such as once-daily subcutaneous Liraglutide 3.0 mg (Saxenda®) and once-weekly subcutaneous Semaglutide 2.4 mg (Wegovy®), were approved by the National Institute of Health and Care Excellence (NICE) as a treatment for obesity and funded by the NHS for 2 years. Our local data shows that Saxenda is effective at reducing body weight and glycaemia in people with obesity and diabetes; however, the supply issues of GLP-1 receptor analogues have contributed to the unavailability of Saxenda and Wegovy in our service. Our patients are devastated that they cannot access NICE-approved GLP-1 receptor analogues for obesity. The 2-year GLP-1 receptor analogue treatment limit for obesity alongside a lack of funded NHS services and supply issues represent barriers to treatment for people living with obesity who have clear medical indications.

Targeting the incretin system in obesity and type 2 diabetes mellitus.

Obesity and type 2 diabetes mellitus (T2DM) are widespread, non-communicable diseases that are responsible for considerable levels of morbidity and mortality globally, primarily in the form of cardiovascular disease (CVD). Changes to lifestyle and behaviour have insufficient long-term efficacy in most patients with these diseases; metabolic surgery, although effective, is not practically deliverable on the scale that is required. Over the past two decades, therapies based on incretin hormones, spearheaded by glucagon-like peptide 1 (GLP1) receptor agonists (GLP1RAs), have become the treatment of choice for obesity and T2DM, and clinical evidence now suggests that these agents have benefits for CVD. We review the latest advances in incretin-based pharmacotherapy. These include 'GLP1 plus' agents, which combine the known advantages of GLP1RAs with the activity of additional hormones, such as glucose-dependent insulinotropic peptide, glucagon and amylin, to achieve desired therapeutic goals. Second-generation non-peptidic oral GLP1RAs promise to extend the benefits of GLP1 therapy to those who do not want, or cannot have, subcutaneous injection therapy. We conclude with a discussion of the knowledge gaps that must be addressed before incretin-based therapies can be properly deployed for maximum benefit in the treatment of obesity and T2DM.

Lipoprotein(a) testing in lipid clinics across the UK: Results of a national survey.

Lipoprotein(a) is an independent risk factor for cardiovascular disease and its use is recommended in national and international guidelines for cardiovascular disease risk stratification. We undertook a survey to understand the availability and application of lipoprotein(a) measurement across UK lipid clinics. Fifty-three out of an estimated 200 lipid clinics (27%) provided responses. Eighty-one percent of 53 clinics had access to lipoprotein(a) measurement. Twenty-seven clinics disclosed the number of lipoprotein(a) tests ordered annually with approximately half of the clinics (52%) requesting 0-250 tests per year. Sixty percent measured lipoprotein(a) once per patient and the leading indication was a personal or family history of premature history of cardiovascular disease in those <60 years old. Sixty-three percent of clinics that provided comments with lipoprotein(a) results graded cardiovascular risk as per the HEART UK consensus statement. Sixty percent of clinics performed family cascade testing on lipoprotein(a) results ≥200 nmol/L. Lipoprotein(a) was reported in nmol/L, mg/dL, or mg/L by 48%, 24%, and 28% of responding clinics, respectively. National effort is required to provide universal access to lipoprotein(a) measurement and to harmonise the clinical application of this data.

Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215, in adults with overweight or obesity: Results from a phase 1 randomized clinical trial.

AIMS: To determine whether a continuous infusion of a glucagon-like peptide receptor (GLP-1R)/glucagon receptor (GCGR) co-agonist, G3215 is safe and well tolerated in adults with overweight or obesity. METHODS: A phase 1 randomized, double blind, placebo-controlled trial of G3215 in overweight or obese participants, with or without type 2 diabetes. RESULTS: Twenty-six participants were recruited and randomized with 23 completing a 14-day subcutaneous infusion of G3215 or placebo. The most common adverse events were nausea or vomiting, which were mild in most cases and mitigated by real-time adjustment of drug infusion. There were no cardiovascular concerns with G3215 infusion. The pharmacokinetic characteristics were in keeping with a continuous infusion over 14 days. A least-squares mean body weight loss of 2.39 kg was achieved with a 14-day infusion of G3215, compared with 0.84 kg with placebo infusion (p < .05). A reduction in food consumption was also observed in participants receiving G3215 and there was no deterioration in glycaemia. An improved lipid profile was seen in G3215-treated participants and consistent with GCGR activation, a broad reduction in circulating amino acids was seen during the infusion period. CONCLUSION: An adaptive continuous infusion of the GLP-1/GCGR co-agonist, G3215, is safe and well tolerated offering a unique strategy to control drug exposure. By allowing rapid, response-directed titration, this strategy may allow for mitigation of adverse effects and afford significant weight loss within shorter time horizons than is presently possible with weekly GLP-1R and multi-agonists. These results support ongoing development of G3215 for the treatment of obesity and metabolic disease.

Increased glycemic variability in pregnant women with Roux-en-Y gastric bypass compared with sleeve gastrectomy.

INTRODUCTION: Bariatric surgery is associated with adverse pregnancy outcomes such as reduced birth weight and premature birth. One possible mechanism for this is increased glycemic variability (GV) which occurs after bariatric surgery. The objective of this study was to compare the effect of Roux-en-Y gastric bypass (RYGB) versus vertical sleeve gastrectomy (SG) on GV during pregnancy and to investigate the relationships of GV, type of bariatric surgery and maternal and neonatal outcomes. RESEARCH DESIGN AND METHODS: Fourteen pregnant women after RYGB and 14 after SG were investigated with continuous glucose monitoring in their second or third trimester in this observational study carried out as part of routine clinical care. RESULTS: Pregnant women with RYGB had similar mean interstitial glucose values but significantly increased indices of GV and a lower %time in range 3.9-7.8 mmol/L (70-140 mg/dL), compared with SG. CONCLUSIONS: Pregnant women who have undergone RYGB have greater GV during pregnancy compared with those who have undergone SG. Further research is needed to establish the relationship between GV and pregnancy outcomes to determine the preferred bariatric operation in women of reproductive age, and whether interventions to reduce GV might improve outcomes.

The current status of lipoprotein (a) measurement in clinical biochemistry laboratories in the UK: Results of a 2021 national survey.

BACKGROUND: Lipoprotein(a) (Lp(a)) is now established as a causal risk factor for cardiovascular disease (CVD) and accurate laboratory measurement is of pivotal importance in reducing Lp(a) associated risk. The consensus statement by HEART UK in 2019 included recommendations to improve standardisation of clinical laboratory measurement and reporting of Lp(a). METHODS: A 16 question, electronic audit survey was circulated to 190 accredited clinical biochemistry laboratories to assess the adoption of these recommendations in the UK. RESULTS: Responses were received from 65 of 190 laboratories (34%). Only 5 (8%) did not offer Lp(a) measurement. Of those providing the test, 23% (n = 14) offered an in-house service (IHS), the remaining laboratories (77%; n = 46) used an external referral service (ERS). The majority (10 of 14 or 71%) of IHS laboratories responded with details of their method, stating whether it minimised sensitivity to the effect of Lp(a) isoform size and used calibrators certified for traceability to the WHO/IFCC reference material, however, only a minority ERS laboratories (13 of the 46 or 28%) were able to specify the method used by their referral laboratory. Of the laboratories who specified their reporting units, 6 of 10 IHS and 7 of 23 ERS laboratories reported in nmol/L. Among the 60 laboratories who responded, the HEART UK recommendations appear to have been adopted in full by only 3 IHS laboratories. CONCLUSIONS: Further efforts are needed to standardise the measurement and reporting of Lp(a) so that results and interpretation are comparable across clinical biochemistry laboratories in the UK.

[Pharmacotherapy of obesity-Competition to bariatric surgery or a meaningful supplement?] / Medikamentöse Therapie der Adipositas ­ Konkurrenz zur bariatrischen Chirurgie oder sinnvolle Ergänzung?

Obesity is a complex chronic disease and requires a long-term multimodal approach. The current treatment algorithm for treatment of obesity mainly consists of a stepwise approach, which starts with a lifestyle intervention followed by or combined with medication treatment, whereas bariatric surgery is often reserved for the last option. This article provides an overview of the currently available conservative medicinal treatment regimens and the currently approved medications as well as medications currently undergoing approval studies with respect to the efficacy and possible side effects. Special attention is paid to the importance of combination treatment of pharmacotherapy and surgery in the sense of a multimodal treatment. The data so far show that using a multimodal approach an improvement in the long-term weight loss and metabolic benefits can be achieved for the patients.

Obesity management for the gastroenterologist.

Obesity has reached epidemic levels in the United Kingdom. Obesity is associated with important gastrointestinal and hepatic complications which are common and can present sooner than cardiometabolic disease but often the underlying obesity remains untreated. Given that gastroenterologists and hepatologists will be at the forefront of obesity management we present an overview encompassing obesity pathophysiology, medical and surgical treatment options as well as the role of endobariatrics and the gut microbiome.

The use of whole blood capillary samples to measure 15 analytes for a home-collect biochemistry service during the SARS-CoV-2 pandemic: A proposed model from North West London Pathology.

BACKGROUND: The COVID-19 pandemic has drastically changed the delivery of secondary care services. Self-collection of capillary blood at home can facilitate the monitoring of patients with chronic disease to support virtual clinics while mitigating the risk of SARS-CoV-2 infection and transmission. OBJECTIVE: To investigate the comparability of whole blood capillary and plasma venous samples for 15 routinely used biochemical analytes and to develop and pilot a user-friendly home-collection kit to support virtual outpatient clinical services. METHODS: To investigate the comparability of whole blood capillary and plasma venous samples for 15 routinely requested biochemical analytes, simultaneous samples of venous and capillary blood were collected in EDTA and lithium-heparin plasma separation tubes that were of 4-6 mL and 400-600 µL draw volume, respectively. Venous samples were analysed within 4 h of collection while capillary samples were kept at ambient temperature for three days until centrifugation and analysis. Analyte results that were comparable between the matrices were then piloted in a feasibility study in three outpatient clinical services. RESULTS: HbA1c, lipid profile and liver function tests were considered comparable and piloted in the patient feasibility study. The home-collect kit demonstrated good patient usability. CONCLUSION: Home collection of capillary blood could be a clinically-useful tool to deliver virtual care to patients with chronic disease.

Adult obesity complications: challenges and clinical impact.

The complications associated with adult obesity are overwhelming national healthcare systems. No country has yet implemented a successful population-level strategy to reverse the rising trends of obesity. This article presents epidemiological data on the complications of adult obesity and discusses some of the challenges associated with managing this disease at a population and individual level.