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Article ; Online: Drugs Affecting Body Weight, Body Fat Distribution, and Metabolic Function-Mechanisms and Possible Therapeutic or Preventive Measures: an Update.

Verhaegen, Ann A / Van Gaal, Luc F

Current obesity reports

2021 Volume 10, Issue 1, Page(s) 1–13

Abstract: Purpose of review: Weight gain and body fat redistribution are common side effects of many widely used drugs. We summarize recent literature on prevalence data and mechanisms associated with drug-induced body fat changes and mechanisms to prevent or ... ...

Abstract	Purpose of review: Weight gain and body fat redistribution are common side effects of many widely used drugs. We summarize recent literature on prevalence data and mechanisms associated with drug-induced body fat changes and mechanisms to prevent or treat metabolic side effects. Recent findings: The highest prevalence of metabolic complications is seen with antipsychotics and antiretroviral drugs used in the treatment of HIV and may, at least partly, be responsible for the increased risk for co-morbid diseases such as diabetes, steatosis of the liver, and cardiovascular disease. The pathogenetic mechanisms leading to weight gain from antipsychotics are increasingly known and help to unravel the complex interaction that exists between psychopathology and metabolic complications. Although the classic lipodystrophy mainly occurred with older HIV drugs, also with the newer HIV treatment, weight gain seems to be a major side effect. Early detection of the metabolic consequences of drugs can lead to an early diagnosis of the complications and their treatment. Different medications, including the newer antidiabetics, are being studied in the therapy of drug-induced obesity. Future research should focus on identifying individuals at risk for metabolic side effects and on early markers to identify individuals with side effects so that timely treatment of metabolic complications can be initiated.
MeSH term(s)	Adrenal Cortex Hormones/adverse effects ; Animals ; Anti-Retroviral Agents/adverse effects ; Antidepressive Agents/adverse effects ; Antipsychotic Agents/adverse effects ; Body Fat Distribution ; Body Weight/drug effects ; Cardiovascular Diseases ; Diabetes Mellitus ; HIV Infections/drug therapy ; Humans ; Insulin Resistance ; Lithium/adverse effects ; Metabolic Diseases/etiology ; Obesity ; Weight Gain/drug effects
Chemical Substances	Adrenal Cortex Hormones ; Anti-Retroviral Agents ; Antidepressive Agents ; Antipsychotic Agents ; Lithium (9FN79X2M3F)
Language	English
Publishing date	2021-01-05
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2162-4968
ISSN (online)	2162-4968
DOI	10.1007/s13679-020-00419-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Efficacy and safety of high-dose glucagon-like peptide-1, glucagon-like peptide-1/glucose-dependent insulinotropic peptide, and glucagon-like peptide-1/glucagon receptor agonists in type 2 diabetes.

De Block, Christophe E M / Dirinck, Eveline / Verhaegen, Ann / Van Gaal, Luc F

Diabetes, obesity & metabolism

2022 Volume 24, Issue 5, Page(s) 788–805

Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in high-risk individuals. With currently available GLP-1 RAs, 51%-79% of subjects achieve ... ...

Abstract	Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in high-risk individuals. With currently available GLP-1 RAs, 51%-79% of subjects achieve an HbA1c target of less than 7.0% and 4%-27% lose 10% of body weight, illustrating the need for more potent agents. Three databases (PubMed, Cochrane, Web of Science) were searched using the MESH terms 'glucagon-like peptide-1 receptor agonist', 'glucagon receptor agonist', 'glucose-dependent insulinotropic peptide', 'dual or co-agonist', and 'tirzepatide'. Quality of papers was scored using PRISMA guidelines. Risk of bias was evaluated using the Cochrane assessment tool. An HbA1c target of less than 7.0% was attained by up to 80% with high-dose GLP-1 RAs and up to 97% with tirzepatide, with even up to 62% of people with T2D reaching an HbA1c of less than 5.7%. A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high-dose GLP-1 RAs or tirzepatide, respectively. The glucose- and weight-lowering effects of the GLP-1/glucagon RA cotadutide equal those of liraglutide 1.8 mg. Gastrointestinal side effects of high-dose GLP-1 RAs and co-agonists occurred in 30%-70% of patients, mostly arising within the first 2 weeks of the first dose, being mild or moderate in severity, and transient. The development of high-dose GLP-1 RAs and the dual GLP-1/glucose-dependent insulinotropic peptide RA tirzepatide resulted in increasing numbers of people reaching HbA1c and body weight targets, with up to 62% attaining normoglycaemia with 15-mg tirzepatide. Whether this will also translate to better cardiovascular outcomes and affect treatment guidelines remains to be studied.
MeSH term(s)	Blood Glucose ; Diabetes Mellitus, Type 2/chemically induced ; Diabetes Mellitus, Type 2/drug therapy ; Gastric Inhibitory Polypeptide/therapeutic use ; Glucagon-Like Peptide 1/adverse effects ; Glucagon-Like Peptide-1 Receptor/agonists ; Humans ; Hypoglycemic Agents/adverse effects ; Receptors, Glucagon
Chemical Substances	Blood Glucose ; Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents ; Receptors, Glucagon ; Gastric Inhibitory Polypeptide (59392-49-3) ; Glucagon-Like Peptide 1 (89750-14-1)
Language	English
Publishing date	2022-01-21
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.14640
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Article ; Online: Efficacy and safety of exenatide once weekly: an overview of the DURATION trials.

De Block, Christophe Em / Van Gaal, Luc F

Expert review of endocrinology & metabolism

2019 Volume 7, Issue 6, Page(s) 611–623

Abstract: Diabetes management involves controlling glycemia and cardiometabolic risk factors. In the DURATION trials, the efficacy and safety of exenatide (EX) once weekly (q.w.), a new long-acting glucagon-like-peptide-1 receptor agonist, was studied as ... ...

Abstract	Diabetes management involves controlling glycemia and cardiometabolic risk factors. In the DURATION trials, the efficacy and safety of exenatide (EX) once weekly (q.w.), a new long-acting glucagon-like-peptide-1 receptor agonist, was studied as monotherapy or as add-on to metformin with or without sulfonylurea, and compared with oral (metformin, pioglitazone or sitagliptin) and injectable antidiabetic drugs (EX twice daily [EX b.i.d.], liraglutide and insulin glargine). EX q.w. reduced HbA
Language	English
Publishing date	2019-02-12
Publishing country	England
Document type	Journal Article
ISSN	1744-8417
ISSN (online)	1744-8417
DOI	10.1586/eem.12.51
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Article: Therapeutic approaches for non-alcoholic steatohepatitis.

Van Gaal, Luc F / Mertens, Jonathan / Francque, Sven / De Block, Christophe

Therapeutic advances in endocrinology and metabolism

2021 Volume 12, Page(s) 20420188211034300

Abstract: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been reported as a novel worldwide epidemic, very often associated with obesity, metabolic syndrome, and type 2 diabetes. Both conditions have also been shown to be ... ...

Abstract	Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been reported as a novel worldwide epidemic, very often associated with obesity, metabolic syndrome, and type 2 diabetes. Both conditions have also been shown to be associated with a number of endocrine pathologies. Despite the epidemic, the complex pathophysiology and major complications, ranging from metabolic disturbances (diabetes and more) to cardiovascular disease, people with NASH are left with very few management options. The best and most approved therapeutic option is lifestyle intervention. Although pharmacotherapies based on pathophysiological background are in development, response rates appear modest, mainly for fibrosis treatment, which is the reason for lack of approved drug therapy. Previous drugs analyzed, such as pioglitazone and vitamin E, show weak efficacy. From different phase II trials, antidiabetic (injectable) drugs seem to be promising, both in mono- or bitherapy. Also, derivatives of peroxisome proliferator-activated receptors may have an interesting future, as well. For that reason, more focus should be given on prevention of this novel disease entity. In view of this booming epidemic, with a background of obesity and type 2 diabetes, and the important medical consequences, early recognition, prevention and intervention of NAFLD/NASH seems appropriate. In this review, we will focus on the different current and future therapeutic intervention options, taking into consideration the complex pathophysiology of this disease.
Language	English
Publishing date	2021-09-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2554822-0
ISSN	2042-0196 ; 2042-0188
ISSN (online)	2042-0196
ISSN	2042-0188
DOI	10.1177/20420188211034300
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Article: NAFLD in type 1 diabetes: overrated or underappreciated?

Mertens, Jonathan / Van Gaal, Luc F / Francque, Sven M / De Block, Christophe

Therapeutic advances in endocrinology and metabolism

2021 Volume 12, Page(s) 20420188211055557

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries, affecting 25-30% of the general population and up to 65% in those with obesity and/or type 2 diabetes. Accumulation of visceral adipose tissue and ... ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries, affecting 25-30% of the general population and up to 65% in those with obesity and/or type 2 diabetes. Accumulation of visceral adipose tissue and insulin resistance (IR) contributes to NAFLD. NAFLD is not an innocent entity as it not only may cause nonalcoholic steatohepatitis and cirrhosis but also contribute to cardiovascular morbidity and mortality. More and more people with type 1 diabetes (T1D) are becoming overweight and present with features of IR, but the prevalence and impact of NAFLD in this population are still unclear. The utility of noninvasive screening tools for NAFLD in T1D is being explored. Recent data indicate that based upon ultrasonographic criteria NAFLD is present in 27% (ranging between 19% and 31%) of adults with T1D. Magnetic resonance imaging data indicate a prevalence rate of 8.6% (ranging between 2.1% and 18.6%). There are, however, multiple factors affecting these data, ranging from study design and referral bias to discrepancies in between diagnostic modalities. Individuals with T1D have a 7-fold higher risk of cardiovascular disease (CVD) and cardiovascular mortality is the most prominent cause of death in T1D. Patients with T1D and NALFD are also more prone to develop CVD, but the independent contribution of NAFLD to cardiovascular events has to be determined in this population. Furthermore, limited data in T1D also point towards a 2 to 3 times higher risk for microvascular complications in those with NAFLD. In this article, we will discuss epidemiological and diagnostic challenges of NAFLD in T1D, explore the link between IR and NAFLD and chronic complications, and examine the independent contribution of NAFLD to the presence of macro-, and microvascular complications.
Language	English
Publishing date	2021-11-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2554822-0
ISSN	2042-0196 ; 2042-0188
ISSN (online)	2042-0196
ISSN	2042-0188
DOI	10.1177/20420188211055557
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Article ; Online: Progress and challenges in anti-obesity pharmacotherapy.

Bessesen, Daniel H / Van Gaal, Luc F

The lancet. Diabetes & endocrinology

2017 Volume 6, Issue 3, Page(s) 237–248

Abstract: Obesity is a serious and growing worldwide health challenge. Healthy lifestyle choices are the foundation of obesity treatment. However, weight loss can lead to physiological adaptations that promote weight regain. As a result, lifestyle treatment alone ... ...

Abstract	Obesity is a serious and growing worldwide health challenge. Healthy lifestyle choices are the foundation of obesity treatment. However, weight loss can lead to physiological adaptations that promote weight regain. As a result, lifestyle treatment alone typically produces only modest weight loss that is difficult to sustain. In other metabolic diseases, pharmacotherapy is an accepted adjunct to lifestyle. Several anti-obesity drugs have been approved in the USA, European Union, Australia, and Japan including sympathomimetics, pancreatic lipase inhibitors, GABA
MeSH term(s)	Anti-Obesity Agents/therapeutic use ; Disease Management ; Humans ; Obesity/drug therapy ; Prognosis ; Weight Loss/drug effects
Chemical Substances	Anti-Obesity Agents
Language	English
Publishing date	2017-09-14
Publishing country	England
Document type	Journal Article ; Review
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(17)30236-X
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Article: Copy number variant analysis and expression profiling of the olfactory receptor-rich 11q11 region in obesity predisposition.

Diels, Sara / Huybreghts, Sander / Van Hoorenbeeck, Kim / Massa, Guy / Verrijken, An / Verhulst, Stijn L / Van Gaal, Luc F / Van Hul, Wim

Molecular genetics and metabolism reports

2020 Volume 25, Page(s) 100656

Abstract: Genome-wide copy number surveys associated chromosome 11q11 with obesity. As this is an olfactory receptor-rich region, we hypothesize that genetic variation in olfactory receptor genes might be implicated in the pathogenesis of obesity. Multiplex ... ...

Abstract	Genome-wide copy number surveys associated chromosome 11q11 with obesity. As this is an olfactory receptor-rich region, we hypothesize that genetic variation in olfactory receptor genes might be implicated in the pathogenesis of obesity. Multiplex Amplicon Quantification analysis was applied to screen for copy number variants at chromosome 11q11 in 627 patients with obesity and 330 healthy-weight individuals. A ± 80 kb deletion with an internally 1.3 kb retained segment was identified, covering the three olfactory receptor genes
Language	English
Publishing date	2020-10-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2821908-9
ISSN	2214-4269
ISSN	2214-4269
DOI	10.1016/j.ymgmr.2020.100656
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Article ; Online: Prevalence, risk factors and diagnostic accuracy of non-invasive tests for NAFLD in people with type 1 diabetes.

Mertens, Jonathan / Weyler, Jonas / Dirinck, Eveline / Vonghia, Luisa / Kwanten, Wilhelmus J / Mortelmans, Laura / Peleman, Cedric / Chotkoe, Shivani / Spinhoven, Maarten / Vanhevel, Floris / Van Gaal, Luc F / De Winter, Benedicte Y / De Block, Christophe E M / Francque, Sven M

JHEP reports : innovation in hepatology

2023 Volume 5, Issue 7, Page(s) 100753

Abstract: Background & aims: The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the ... ...

Abstract	Background & aims: The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the prevalence and severity of NAFLD, and to search for factors contributing to NAFLD in people with T1D. Methods: In this prospective cohort study, we consecutively screened 530 adults with T1D from a tertiary care hospital, using ultrasound (US), vibration-controlled transient elastography equipped with liver stiffness measurement (LSM) and controlled attenuation parameter, and the fatty liver index. Magnetic resonance spectroscopy (MRS) was performed in a representative subgroup of 132 individuals to validate the diagnostic accuracy of the non-invasive tests. Results: Based on MRS as reference standard, US identified individuals with NAFLD with an AUROC of 0.98 (95% CI 0.95-1.00, sensitivity: 1.00, specificity: 0.96). The controlled attenuation parameter was also accurate with an AUROC of 0.85 (95% CI 0.77-0.93). Youden cut-off was ≥270 dB/m (sensitivity: 0.90, specificity: 0.74). The fatty liver index yielded a similar AUROC of 0.83 (95% CI 0.74-0.91), but the conventional cut-off used to rule in (≥60) had low sensitivity and specificity (0.62, 0.78). The prevalence of NAFLD in the overall cohort was 16.2% based on US. Metabolic syndrome was associated with NAFLD (OR: 2.35 [1.08-5.12], Conclusions: NAFLD prevalence in individuals with T1D is 16.2%, with approximately one in 10 featuring elevated LSM. US-based screening could be considered in people with T1D and metabolic syndrome. Impact and implications: We aimed to report on the prevalence, disease severity, and risk factors of NAFLD in type 1 diabetes (T1D), while also tackling which non-invasive test for NAFLD is the most accurate. We found that ultrasound is the best test to diagnose NAFLD. NAFLD prevalence is 16.2%, and is associated with metabolic syndrome and BMI. Elevated liver stiffness indicating fibrosis is overall not prevalent in people with T1D (3.8%), but it reaches 13.2% in those with T1D and NAFLD.
Language	English
Publishing date	2023-04-07
Publishing country	Netherlands
Document type	Journal Article
ISSN	2589-5559
ISSN (online)	2589-5559
DOI	10.1016/j.jhepr.2023.100753
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Article ; Online: Overweight, obesity, and outcomes: fat mass and beyond.

Van Gaal, Luc F / Maggioni, Aldo P

Lancet (London, England)

2014 Volume 383, Issue 9921, Page(s) 935–936

MeSH term(s)	Body Mass Index ; Coronary Disease/etiology ; Humans ; Overweight/complications ; Stroke/etiology
Language	English
Publishing date	2014-03-15
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(13)62076-0
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Ua VI Zs.5: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 94: Show issues

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Article ; Online: Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.

Wilding, John P H / Batterham, Rachel L / Davies, Melanie / Van Gaal, Luc F / Kandler, Kristian / Konakli, Katerina / Lingvay, Ildiko / McGowan, Barbara M / Oral, Tugce Kalayci / Rosenstock, Julio / Wadden, Thomas A / Wharton, Sean / Yokote, Koutaro / Kushner, Robert F

Diabetes, obesity & metabolism

2022 Volume 24, Issue 8, Page(s) 1553–1564

Abstract: Aim: To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension.: Materials and methods: STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m: Results: ... ...

Abstract	Aim: To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension. Materials and methods: STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m Results: Extension analyses included 327 participants. From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo. Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables. Conclusions: One year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.
MeSH term(s)	Adult ; Cardiovascular Diseases/epidemiology ; Diabetes Mellitus/epidemiology ; Glucagon-Like Peptides/administration & dosage ; Humans ; Weight Gain
Chemical Substances	semaglutide (53AXN4NNHX) ; Glucagon-Like Peptides (62340-29-8)
Language	English
Publishing date	2022-05-19
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.14725
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