topiramate and dapagliflozin

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

Topics: Anti-Obesity Agents; Bariatric Surgery; Benzazepines; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Exercise; Feeding Behavior; Female; Fructose; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycated Hemoglobin; Homeostasis; Humans; Islet Amyloid Polypeptide; Lactones; Male; Minimally Invasive Surgical Procedures; Obesity, Morbid; Orlistat; Phentermine; Receptors, Glucagon; Topiramate; Treatment Outcome; Weight Loss

Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms.. The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS.. Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample.. EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs.. Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.

Topics: Adolescent; Adult; Benzhydryl Compounds; Blood Glucose; Drug Therapy, Combination; Exenatide; Female; Glucose Tolerance Test; Glucosides; Humans; Hypoglycemic Agents; Metformin; Middle Aged; Obesity; Phentermine; Polycystic Ovary Syndrome; Prospective Studies; Single-Blind Method; Topiramate; Treatment Outcome; Weight Loss; Young Adult