obesity and weight management

obesity risks

cardiovascular disease:
- in white Causasians, cardiovascular risk increases by 13% for every 5.2 kg/m2 increase in women and 4.3 kg/m2 in men above an optimum level of 22-23 kg/m2 and, compared to women and men with waist circumferences of 74 and 83 cm respectively, the CVD risk increased by 16% in women and 10% in men for every 12.6 cm and 11.4 cm increase in waist circumference for women and men respectively.¹⁾
cancer
diabetes
insulin resistance
high sugar or fructose diet
- small intakes of sucrose or fructose are converted to glucose by enterocytes in the small bowel which is then metabolised by the whole body as needed
- excessive intakes of sucrose or fructose results in fructose being absorbed into the circulation and then it must be metabolised into fat primarily within the liver
osteoarthritis
deep venous thrombosis (DVT)
mental health issues
medical iatrogenic risks
- vascular access issues
- pressure sores
- complexity of medical and surgical procedures increases
- ultrasound not as readily diagnostic

lorcaserin is a selective 5-HT2C agonist with 15x more activity than on 5-HT2A receptors, and 100x more activity than on 5-HT2B receptors
- under trial for obesity management in 2010²⁾ - appears to reduce weight by ~6kg in 1 year compared with 2kg for a placebo with almost 50% of patients losing at least 5% body weight compared with only 20% of those on placebo.

Akkermansia muciniphila appears to improve pre-diabetes and reduce weight in an initial study ³⁾

fenfluramine and dexfenfluramine was approved for Mx of obesity in the USA by FDA in 1973 and 1996 respectively
both were withdrawn in 1997 after they were found to cause serotonin associated cardiac valvulopathy which is thought to be due to agonism of 5-HT2B receptors, and is similar to that seen in carcinoid heart disease and ergot-alkaloid induced heart disease.

rimonabant was withdrawn from the market in Europe because of an increased risk of depression, anxiety and suicidal ideation.

the serotonin and noradrenaline reuptake inhibitor, sibutramine, was removed from the European market after a 100,000 patient, 6-year SCOUT study showed an increased risk of serious nonfatal cardiovascular events such as stroke or heart attack.

¹⁾

²⁾

NEJM July 2010 363:3

³⁾