Obesity is a health problem that is increasing worldwide and has high socioeconomic impact. In Sweden, obesity costs the society 70 billion SEK every year. For the year 2030, the Institute for Health and Medical Care Economics predicts that obesity can cost the society up to 17 billion SEK more than in 2018. In Sweden, 52% of the citizens 16-84 years of age are either overweight or obese.  The main factor behind obesity is still unidentified. What is known, and almost self-evident, is that weight gain occurs when energy consumption is lower than energy intake. The calorie intake during a day should be 1600-3000 calories and physical activity is important. For weight loss, the focus is mostly on calorie intake, but it is also important to consider the metabolic homeostasis which is regulated by hormones. Obesity can occur when there is a disturbance in the homeostatic mechanisms. One of the most important regulatory hormones is glucagon-like-peptide-1 (GLP-1) which stimulates satiety. Liraglutide and semaglutide are both GLP-1-analogues and are used in the treatment of type 2 diabetes. Liraglutide is also indicated in obesity and semaglutide as an anti-obesity drug has just undergone a phase 3 study. The mechanism of action of GLP-1-analogues in obesity is to stimulate a feeling of satiety, which leads to a lower energy intake and thus weight loss.  The aim of this thesis was to evaluate whether semaglutide can be used as an anti-obesity drug and the effect and safety of the substance compared with the already approved drug liraglutide.  The thesis is a literature study that uses five randomized clinical trials from the database PubMed. Of the six scientific articles, two examine liraglutide for 56 weeks, two semaglutide for 68 weeks and one both drugs for 52 weeks.  All studies demonstrate that semaglutide has a better effect on reducing body weight and waist measurement than liraglutide. In study 5, semaglutide above 1,4 mg per week is shown to have a statistically significantly better weight loss effect compared to liraglutide. Gastrointestinal side effects were the most common side effects in all included studies. The majority of these were of mild or moderate intensity. Of the gastrointestinal side effects, nausea was most common. In the semaglutide groups, the total side effects were slightly more frequent than in the liraglutide groups, which is mainly shown in study 5. Possible factors affecting the results is whether the participants receive IBT or lifestyle advice in combination with the treatment.  Conclusions that can be drawn from the studies is that semaglutide is more effective in terms of weight loss and reduction of waist measurements compared to liraglutide. The adverse reactions were generally similar between semaglutide and liraglutide. Semaglutide should currently be administered with caution and under supervision. More studies need to be conducted to control the dosage and safety.

Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2. In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery. In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS). In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms. In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response. In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.