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Obesity Treatments to Improve Type 1 Diabetes (OTID): a randomized controlled trial of the combination of glucagon-like peptide 1 analogues and sodium-glucose cotransporter 2 inhibitors-protocol for Obesity Treatments to Improve Type 1 Diabetes (the OTID trial).
Al-Ozairi, E, Narula, K, Miras, AD, Taghadom, E, Samad, AE, Al Kandari, J, Alyosef, A, Mashankar, A, Al-Najim, W, le Roux, CW
Trials. 2024;(1):129
Abstract
BACKGROUND The guidelines of the American Diabetes Association and European Association for the Study of Diabetes suggest that patients with obesity type 2 diabetics and chronic kidney disease need either glucagon-like peptide 1 receptor analogues or sodium-glucose cotransporter-2 inhibitors. If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors is not well researched, and hence, the impact of the guidelines is limited. The aim of this randomized controlled trial is to test the impact of the combination of glucagon-like peptide 1 receptor analogues/sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage, in patients with type 1 diabetes and chronic kidney disease. In addition, we will explore the associated changes in the metabolic pathways with each of the treatments used in this randomized controlled trial. METHODS In this 6-month randomized control trial, 60 participants aged between 21 and 65 years, with a body mass index above 25 kg/m2, and type 1 diabetics with chronic kidney disease will be randomized to receive 1 of 5 possible treatments: (1) standard care (control), (2) glucagon-like peptide 1 receptor analogues alone, (3) sodium-glucose cotransporter-2 inhibitors alone, (4) combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors and (5) combination of glucagonlike peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors with intensive lifestyle advice. The primary objective will be the percentage change in total body weight from baseline at 6 months. The secondary objectives are to compare the change in glycaemia; blood pressure; dyslipidaemia; albuminuria; proportion of participants reaching weight loss of ≥ 5%, ≥ 10% and ≥ 15%; and change in BMI (kg/m2) from baseline and change in waist circumference (cm). All the experiments will be conducted at the Dasman Diabetes Institute after approval from the local research and ethics committee. DISCUSSION The present randomized controlled trial aims to investigate the impact of the combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage in patients with type 1 diabetes mellitus and chronic kidney disease, as well as exploring the associated changes in the metabolic pathways with each of the treatments used. This study addresses the current gap in the evidence base regarding the combination of these two drugs, which is particularly relevant given the American Diabetes Association and European Association for the Study of Diabetes guidelines recommending their combined use for patients with obesity, type 2 diabetes, and chronic kidney disease who do not achieve metabolic control with either drug alone. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT05390307 Trial registration date - 25th May 2022.
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The emergence of obesity in type 1 diabetes.
Kueh, MTW, Chew, NWS, Al-Ozairi, E, le Roux, CW
International journal of obesity (2005). 2024;(3):289-301
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Abstract
Obesity, a chronic low-grade inflammatory disease represented by multifactorial metabolic dysfunctions, is a significant global health threat for adults and children. The once-held belief that type 1 diabetes is a disease of people who are lean no longer holds. The mounting epidemiological data now establishes the connection between type 1 diabetes and the subsequent development of obesity, or vice versa. Beyond the consequences of the influx of an obesogenic environment, type 1 diabetes-specific biopsychosocial burden further exacerbates obesity. In the course of obesity management discussions, recurring challenges surfaced. The interplay between weight gain and escalating insulin dependence creates a vicious cycle from which patients struggle to break free. In the absence of weight management guidelines and regulatory approval for this population, healthcare professionals must navigate the delicate balance between benefits and risks. The gravity of this circumstance highlights the importance of bringing these topics to the forefront. In this Review, we discuss the changing trends and the biopsychosocial aspects of the intersection between type 1 diabetes and obesity. We highlight the evidence supporting the therapeutic means (i.e., exercise therapy, nutritional therapy, adjunct pharmacotherapy, and bariatric surgery) and directions for establishing a more robust and safer evidence-based approach.
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A review of the evidence on cardiovascular outcomes from obesity treatment.
Abdul Wahab, R, le Roux, CW
Obesity pillars. 2023;:100071
Abstract
BACKGROUND Obesity is a chronic disease with a myriad of complications including cardiovascular disease. There is a growing interest to examine if obesity treatment is associated with cardiovascular outcomes. METHODS In this narrative review, we focused on randomized controlled trials (RCT) with cardiovascular outcomes (CVO) from lifestyle intervention, bariatric surgery, glucagon-like peptide-1 analogues (GLP-1a) and other pharmacotherapy. Additionally, we provide a comprehensive look into the RCT of sodium glucose cotransporter 2 inhibitors (SGLT2i) and CVO in obesity, while also summarizing several ongoing randomized cardiovascular outcome controlled trials for the pharmacological treatment of obesity. RESULTS To date, the results from the randomized controlled trials supported the association between obesity treatment and cardiovascular outcomes. Studies have large sample sizes, conducted over long duration, with the majority demonstrating superiority in primary cardiovascular outcome end points compared to placebo. CONCLUSION Future data from several ongoing anti-obesity medications cardiovascular outcome trials such as SELECT, SURPASS, SUMMIT and SURMOUNT-MMO hold promises. Further studies are warranted to investigate the long term cardiovascular outcomes following lifestyle intervention and bariatric surgery.
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Achieving consensus on the language of obesity: a modified Delphi study.
Jepsen, CH, Bowman-Busato, J, Allvin, T, Arthurs, N, Goossens, GH, Govers, E, Jaghutriz, BA, Mooney, V, Van der Schueren, B, le Roux, CW
EClinicalMedicine. 2023;:102061
Abstract
BACKGROUND Obesity is recognized by the World Health Organization as a chronic disease. As such, it should be referred to using the language of chronic diseases, with correct and established terminology and definitions. This study was designed to map the current language used to discuss obesity and to compare this with the standard language used for chronic disease. METHODS We performed a modified Delphi study to identify the language of chronic disease that is being used in the context of obesity, and to identify discrepancies and potential use of inadequate language with respect to the standard language used for chronic diseases. Participants (n = 24) were identified from relevant stakeholder groups and desk research, and included patients, healthcare professionals, policymakers, researchers, industry, and payers (social insurers) of 18 nationalities/regions in Europe, North/South America, and South Africa. Participants were enrolled between 20.10.2020 and 30.10.2020. The study comprised two rounds of qualitative surveys. In Round 1, participants responded to six open-ended questions. Round 2 comprised 38 statements based on key terms/themes identified in Round 1 and covered the definition, causes, progression, treatment, management, and complications of obesity. Consensus was defined as ≥70% participant agreement on a statement. FINDINGS All participants completed Round 1 and 23 participants completed Round 2. In Round 2, consensus was reached for 28 of the 38 statements. Participants reached a consensus regarding the use of statements that acknowledge the heterogeneous nature of obesity, but not on the use of statements that: defined obesity based on body mass index; regarded psychological, physical, or physiological factors among the main causes of obesity; or implied that weight loss should be the aim of obesity treatment. INTERPRETATION This study uses expert consensus to provide insight into the language used to describe obesity as a chronic disease, and forms the basis for a unified language of obesity. FUNDING Innovative Medicines Initiative, Novo Nordisk A/S.
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Food preferences after bariatric surgery: a review update.
Alabduljabbar, K, Al-Najim, W, le Roux, CW
Internal and emergency medicine. 2023;(2):351-358
Abstract
Obesity is a serious and global health problem. The multiple complications of obesity reduce quality of life and increase mortality. Bariatric surgery is one of the best treatment options for obesity management. Bariatric surgery helps people reduce their caloric intake by treating the disease of obesity effectively, in part by increasing signaling from the gut to the brain. The most frequent surgical options are Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). There is controversy regarding changes in food preferences and selection after bariatric surgery. In this review, we aim to outline the changes in food intake and selection, clarify the behavior changes in food intake, and assess the potential mechanisms responsible for these changes in patients after bariatric surgery.
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Laparoscopic adjustable gastric banding with liraglutide in adults with obesity and type 2 diabetes (GLIDE): a pilot randomised placebo controlled trial.
Coelho, C, Dobbie, LJ, Crane, J, Douiri, A, Learoyd, AE, Okolo, O, Panagiotopoulos, S, Pournaras, DJ, Ramar, S, Rubino, F, et al
International journal of obesity (2005). 2023;(11):1132-1142
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Abstract
INTRODUCTION Obesity drives type 2 diabetes (T2DM) development. Laparoscopic adjustable gastric banding (LAGB) has lower weight reduction than other bariatric procedures. Liraglutide, a GLP-1 receptor agonist, improves weight and glycaemic control in patients with T2DM. This study aimed to determine the efficacy and safety of liraglutide 1.8 mg in participants undergoing LAGB. METHODS GLIDE, a pilot randomised, double-blind, placebo-controlled trial, evaluated LAGB with either liraglutide 1.8 mg or placebo in participants with T2DM and obesity. Participants were randomised (1:1) to 6-months therapy post-LAGB, with further 6 months off-treatment follow-up. The primary outcome was change in HbA1c from randomisation to the end of treatment, secondary outcomes included body weight change. A sample size of 58 (29 per group) had 80% power to detect a 0.6% difference in HbA1c between groups. RESULTS Twenty-seven participants were randomised to liraglutide (n = 13) or placebo (n = 14). Multivariate analysis showed no difference between placebo and liraglutide arms in HbA1c at 6 months (HbA1c:0.2 mmol/mol, -11.3, 11.6, p = 0.98) however, at 12 months HbA1c was significantly higher in the liraglutide arm (HbA1c:10.9 mmol/mol, 1.1, 20.6, p = 0.032). There was no difference between arms in weight at 6 months (BW:2.0 kg, -4.2, 8.1, p = 0.50), however, at 12 months weight was significantly higher in the liraglutide arm (BW:8.2 kg, 1.6, 14.9, p = 0.02). There were no significant differences in adverse events between groups. CONCLUSIONS Our pilot data suggest no additional improvement in glycaemic control or BW with LAGB and liraglutide therapy. However, this trial was significantly underpowered to detect a significant change in the primary or secondary outcomes. Further trials are needed to investigate whether GLP-1 agonists, and particularly with more effective weekly agents (i.e. semaglutide or tirzepatide), are of benefit following metabolic surgery. CLINICAL TRIAL REGISTRATION EudraCT number 2015-005402-11.
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Effect of Bariatric Surgery on Serum Amyloid A Protein: a Systematic Review and Meta-analysis.
Jamialahamdi, T, Mirhadi, E, Atkin, SL, le Roux, CW, Kroh, M, Almahmeed, W, Eid, AH, Sahebkar, A
Obesity surgery. 2023;(11):3602-3610
Abstract
BACKGROUND Obesity is a chronic inflammatory condition and this meta-analysis evaluated the impact of bariatric surgery on SAA. METHODS Studies included all types of bariatric surgery where SAA was measured before and after the surgical procedure. RESULTS Meta-analysis of 11 clinical studies (n = 394 individuals) confirmed a significant reduction in SAA following bariatric surgery (SMD: - 0.971, 95% CI: - 2.721, 0.779, p < 0.001). Meta-regression did not show any association between the changes in BMI and the absolute difference in SAA levels. No relationship between the changes in SAA and the length of follow-up was found. CONCLUSION Bariatric surgery significantly improved SAA. The decrease in SAA was not related to time after surgery or changes in BMI. Bariatric surgery may thus have an independent effect on SAA.
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Pharmacotherapy before and after bariatric surgery.
Alabduljabbar, K, le Roux, CW
Metabolism: clinical and experimental. 2023;:155692
Abstract
Diabetes is a chronic disease that affects a vast number of individuals globally, and without optimal treatment, can lead to significant health complications. Moreover, obesity is another chronic disease with several complications, which includes type 2 diabetes. Bariatric surgery is a viable long-term choice for managing diseases such as obesity and type 2 diabetes. However, the impact of pharmacotherapy before and after surgery remains unclear. In this review, we assessed the use of pharmacotherapy in patients with obesity with or without diabetes before and after bariatric surgery, focusing on weight loss, glycemic control, and the risk of postoperative complications. We showed that anti-obesity medication has become increasingly important in managing obesity and type 2 diabetes, both before and after bariatric surgery. The use of preoperative pharmacotherapy can optimize patients for surgery and reduce perioperative complications. Meanwhile, postoperative pharmacotherapy can maximize weight loss, improve metabolic outcomes, and lower the risk of weight regain. Medications such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and combination therapies, are now very effective for treating obesity and type 2 diabetes mellitus. However, optimal timing, duration, and which combinations of pharmacotherapy to use with bariatric surgery remain unclear. Additionally, the long-term safety and efficacy of these treatments should be assessed. Integrating pharmacotherapy with bariatric surgery is a promising approach to managing obesity and type 2 diabetes, providing patients with additional options for achieving sustainable weight loss and improving their metabolic health.
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Stratification of obesity phenotypes to optimize future therapy (SOPHIA).
Tahrani, AA, Panova-Noeva, M, Schloot, NC, Hennige, AM, Soderberg, J, Nadglowski, J, Tarasenko, L, Ahmad, NN, Sleypen, BS, Bravo, R, et al
Expert review of gastroenterology & hepatology. 2023;(10):1031-1039
Abstract
INTRODUCTION Obesity is considered a poor lifestyle choice. 'Obesity' is not a sufficient definition for patients, any more than 'cancer' or 'arthritis' would be. A major obstacle is the lack of understanding of pathogenesis. The disease of obesity is considered homogenous, while response to treatment is thought of as heterogeneous. This can change if pathogenesis, risk profiles for complications, and treatment responses are viewed within the context of obesity consisting of several subsets of disease. AREAS COVERED The European Union-funded Innovative Medicine Initiative project Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy is part of a momentum shift. Operational variables are being used to develop tests and therapies which may allow the prediction of risk of obesities and the prediction of response to obesity treatments. However, changing stakeholder perspectives on obesity may require more than high-quality data and analysis. EXPERT OPINION For patients to benefit, clinicians need to integrate evidence-based treatments and payers need to reimburse the management of the disease of obesity. This will generate commercial opportunities for industry. We need to involve stakeholders (patients, clinicians, regulators, payer, patient organisations) to create a shared value for mutual gain.
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Weight loss to disrupt type 2 diabetes.
Alsaqaaby, MS, le Roux, CW
Diabetology international. 2023;(3):217-223
Abstract
Obesity is now recognised as a disease associated with significant morbidity and mortality. One of the most common metabolic complications of obesity is type 2 diabetes, because the two disease share similar pathophysiology. Weight loss is known to ameliorate the metabolic abnormalities underlying type 2 diabetes and improve glycemic control. A 15% or greater total body weight loss (TBWL) in patients with type 2 diabetes will have a disease-modifying effect, a result that is incomparable with other hypoglycemic-lowering interventions. Moreover, in patients with diabetes and obesity, weight loss exerts benefits beyond glycemic control and improves cardiometabolic disease risk factors and well-being. We review evidence supporting the role of intentional weight loss in managing type 2 diabetes. We suggest that many people with type 2 diabetes would benefit from an additional weight-based approach to managing their diabetes. Therefore, we proposed a weight-based treatment goal for patients with type 2 diabetes and obesity.