Obesity is on the rise worldwide and is one of the greatest public health challenges of our time. In addition to dietary changes and exercise, GLP-1 agonists are a new tool in the repertoire of individualized obesity therapy. New study data show that durable weight control can be achieved through multimodal combination therapy.
According to projections, around 20% of the world’s population will be obese by 2025, according to PD Dr. Katharina Timper, head of the Obesity Research Group, senior physician and head of the obesity consultation at the University Hospital Basel [1]. “Obesity is a plurifactorial disease,” Dr. Timper said. A complex interplay of genetic, epigenetic and acquired factors is thought to be involved. The problem has a very complex psychosocial dimension. For example, overweight people are often confronted with stigmatization (“lazy,” “uneducated,” “undisciplined”), which on the one hand negatively affects the psychological well-being of those affected and contributes to the perpetuation of disordered eating behavior, and on the other hand can result in a loss of trust in health care facilities. All of this can lead to a self-reinforcing vicious cycle, according to an article on this topic published last year in the Lancet [2]. In this context, the speaker emphasizes that an appreciative, empathic, non-stigmatizing attitude towards the patient with obesity is central.
Recognize obesity as a condition requiring treatment
According to the WHO, obesity (box) is a chronic disease caused by a pathological increase in body fat. Overweight and obesity are significant risk factors for a number of chronic and potentially life-threatening diseases, including diabetes, cardiovascular disease, liver disease, and cancer [3]. Furthermore, obese individuals belong to the group of those particularly at risk for covid disease with a severe course, according to the “Allianz Adipositas Schweiz”-a newly launched association with the aim of pooling and coordinating resources in the fight against this widespread disease [4]. Current analyses show that approximately one in three adults in Switzerland is overweight and one in ten is obese [5]. It is a complex and multifactorial problem, and given the observed increase in prevalence, action is needed. In addition to preventive measures, multidisciplinary programs are needed to treat obesity. These are offered and coordinated in particular by specialized centers. “Get help for your patients, refer patients to us,” appeals the head of the obesity consultation at Basel University Hospital. “We track the therapy in close cooperation with you”. Multimodal lifestyle modifications are a key element of obesity treatment. To this end, the Department of Endocrinology, Diabetology and Metabolism works together with specialists from the fields of nutritional counseling, psychosomatics and sports medicine to put together an individually adapted therapy program. A large proportion of obese patients can benefit from such multimodal treatment; in severely obese patients, the option of bariatric surgery can be considered; a prerequisite for coverage by health insurance is BMI ≥35.
GLP-1 analogs to support sustained weight loss.
It is a truism that exercise and nutrition play an important role in weight reduction, although in some cases the implementation of appropriate measures is a challenge bordering on excessive and those affected often fail in the longer term due to the yoyo effect. New therapeutic approaches are needed to achieve effective weight reduction with few side effects and to favorably influence important metabolic processes. Improving blood sugar and fat metabolism is another important treatment goal, along with weight reduction. Much has happened recently in the field of drug treatment of obesity, and the importance of GLP-1 receptor agonists has increased. “Support lifestyle changes with medication with GLP-1 analogs,” is one piece of advice from Dr. Timper. The active substances, also known as incretin mimetics, are modeled on the body’s own glucagon-like peptide (GLP). GLP stimulates the secretion of insulin in the pancreas in a glucose-dependent manner and inhibits that of glucagon. In addition, GLP-1 slows gastric emptying, increases the feeling of satiety, and centrally regulates cravings (Fig. 1). GLP-1 analogs have been shown to be effective in the treatment of overweight/obesity in both diabetic and non-diabetic patients due to their appetite suppressant effects. Since April 2020, Saxenda® (liraglutide 3.0 mg), the first GLP-1 analogue used for weight loss, has been on the market in Switzerland and is subject to health insurance coverage [6]. The preparation is eligible for reimbursement under the following conditions: BMI ≥35 (or ≥28 if weight-related comorbidities such as prediabetes or dyslipidemia are present), prescription by a specialist in endocrinology/diabetology, concomitant documented calorie-restricted diet, and increased exercise. The cost of the drug will be passed on by the health insurance company only if after 4 months of treatment, body weight was reduced by at least 7% and by a further 5% after 10 months [7].
Liraglutide and exercise promotion against the yo-yo effect
A 2021 study published in the New England Journal of Medicine demonstrated that the combination of exercise and liraglutide treatment resulted in better weight control than either intervention alone [8]. 195 of 215 study participants achieved at least 5% weight loss after 8 weeks on a calorie-restricted diet. On average, a 12% reduction in body weight was achieved. Subsequently, the subjects were divided into 4 groups and were divided over a period of 52 weeks observed. One group received an exercise program plus placebo, the second received liraglutide monotherapy, the third group received a combination of both interventions, and the fourth group received placebo. A total of 166 participants completed the study. After 1 Year showed that more weight reduction was achieved in all three treatment arms compared to the placebo arm. Whereas significantly greater weight loss was achieved with the combined treatment strategy than with exercise promotion alone (difference -5.4 kg; 95% CI, -9.0 to -1.7; p=0.004). Compared with liraglutide monotherapy, the combination treatment also proved superior, but this difference was not significant (-2.7 kg; 95% CI, -6.3 to 0.8; p=0.13). With regard to the percentage of body fat, the combination group showed a reduction of 3.9 percentage points was achieved, about twice as much as in the exercise group (-1.7 percentage points; 95% CI, -3.2 to -0.2; p=0.02) and the liraglutide group (-1.9 percentage points; 95% CI, -3.3 to -0.5; p=0.009). Improvements in HbA1c, insulin sensitivity, and cardiorespiratory fitness were achieved only by the combined treatment strategy.
Semaglutide, another substance from the group of GLP-1 analogs, has also been used for several years in the treatment of type 2 diabetes. Studies have shown that semaglutide can also be used successfully for weight loss. New data from the STEP study program underscore this [9,10]. In the meantime, applications have been submitted to the European Medicines Agency (EMA) as well as in the United Kingdom and the United States for the extension of marketing authorization for the indication obesity.
Congress: digMedArt21
Literature:
- Timper K: Obesity therapy – State of the (He)art. PD Dr. Katharina Timper, digMedArt21, 23.06.2021
- Albury C, et al: Lancet Diabetes Endocrinol 2020.
- DGVT and DGVT-BV: News from the psychosocial professional and professional policy of DGVT and DGVT-BV. Issue 6/2019 – September 3, 2019
- Allianz Adipositas Schweiz: “Together against obesity”, 04.03.2021
- Matthes KL, et al: The Weight of Switzerland: A Quantitative Synthesis Study of Body Mass Index and Abdominal Circumference and Associated Cofactors in Adult Men and Women in Switzerland. Zurich/Bern: Federal Office of Public Health FOPH 2020.
- www.swissmedicinfo.ch
- Meienberg F: “Drug against obesity newly reimbursed by KK”, www.ksbl.ch/blog/medikament-gegen-adipositas-neu-von-der-kk-verguetet (last accessed 15.07.2021).
- Lundgren JR, et al. Healthy weight loss maintenance with exercise, liraglutide or both combined. N Engl J Med 2021; 384: 1719-1730.
- Wilding JPH, et al. for the STEP 1 Study Group: Once-Weekly Semaglutide in Adults with Overweight or Obesity. NEJM, February 10, 2021. DOI:10.1056/NEJMoa2032183
- Wadden TE, et al: Subcutaneous Semaglutide vs. Placebo as Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity. The STEP 3 Randomized Clinical Trial. DOI:10.1001/jama.2021.1831
- Ghazanfar H, et al: Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Non-Alcoholic Steatohepatitis: A Clinical Review Article. Cureus 2021; 13(5): e15141.
HAUSARZT PRAXIS 2021; 16(8): 18-20 (published 8/18-21, ahead of print).
