title: How to fight obesity with antidiabetic drugs: targeting gut or kidney?
abstract: The increased prevalence of type 2 diabetes follows the increased prevalence of obesity. Both diseases share common pathophysiological pathways; obesity is in most cases the first step, whereas diabetes is the second one. Weight gain occurs during the treatment of diabetes with drugs causing endogenous or exogenous hyperinsulinemia. Insulin and sulfonylurea are making patients more obese and more insulin resistant. Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) and sodium/glucose cotransporter 2 inhibitors (SGLT2 inhibitors) are antidiabetic drugs with weight loss property. GLP-1 agonists mimic an incretin action. They release insulin after a meal during hyperglycemia and suppress glucagon. The weight loss effect is a consequence of central action increased satiety. Some of GLP-1 agonists weight loss is a result of decelerated gastric emptying rate. SGLT2 inhibitors block sodium glucose cotransporter in proximal tubule brush border and produce glucose excretion with urinary loss. Urinary glucose leak results in calories and weight loss. Even a modest weight loss has positive outcome on metabolic features of diabetic patient; such drugs have important role in treatment of type 2 diabetic patients. However, there are some still unresolved questions. The weight loss they produce is modest. Those drugs are expensive and not available to many diabetic patients, they are significantly more expensive compared to "traditional" hypoglycemic drugs. The hypoglycemic endpoint of GLP-1 agonists and SGLT2 inhibitors often requires adding another antidiabetic drug. The most radical and most effective therapy of type 2 diabetes and obesity is bariatric surgery having significant number of diabetes remission.
authors.affiliation: Division of Endocrinology Department of Internal Medicine, University Hospital Centre Zagreb, Croatia - maja.simek@zg.t-com.hr.
authors.forename: M
authors.initials: M
authors.lastname: Baretić
authors.forename: R
authors.initials: R
authors.lastname: Troskot
mesh_terms: D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050110:Bariatric Surgery; D001692:Biological Transport / Q000187:drug effects; D002986:Clinical Trials as Topic; D015897:Comorbidity; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists; D005947:Glucose / Q000378:metabolism; D006029:Glycosuria / Q000139:chemically induced; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000503:physiopathology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D015337:Multicenter Studies as Topic; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology / Q000601:surgery; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use; D015431:Weight Loss
chemical_list: D019440:Anti-Obesity Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide; D005947:Glucose