small intestines, so it can not be used as an oral administration medication to treat diabetes. structural modifications have been made to overcome this instability problem. the most efficient way was to conjugate aryl moiety with glucose moiety since c-glucosides are more stable in the small intestines than o-glucoside derivatives (c-c bond instead of c-o-c bond). phlorizin in the sugar analogues of dapagliflozin, the β-c series are more active than α-c series so it is critical that the β-configuration is at c-1 for the inhibitory activity. both dapagliflozin and empagliflozin contain a chlorine (cl) atom in their chemical structure. cl is a halogen and it has a high electronegativity. this electronegativity withdraws electrons off the bonds and therefore it reduces the metabolism. the cl atom also reduces the ic50 value of the medication so the medication has better activity. the carbon-fluorine bond (c-f) has also has a very low electron density. dapagliflozin empagliflozin for example, in the chemical structure of canagliflozin a fluorine atom is connected to an aromatic ring then the compound is more stable and the metabolism of the compound is reduced. empagliflozin contains a tetrahydrofuran ring but not canagliflozin nor dapagliflozin. canagliflozin in the development of gliflozins the distal ring contains a thiophene ring instead of an aromatic ring. however the final chemical structures of the marketing gliflozins does not contain this thiophene ring. alternative pharmacological actions sglt2 inhibitors increase circulating ketone body concentrations. the cardioprotective effects of sglt2 inhibitors have been attributed to the elevated ketone levels. gliflozins have been posited to exhibit protective effects on the heart, liver, kidneys, anti‐hyperlipidemic, anti‐atherosclerotic, anti‐obesity, anti‐neoplastic effects in in vitro, pre‐clinical, and clinical studies. pleiotropic effects of this class have been attributed to a variety of its pharmacodynamic actions such as natriuresis, hemoconcentration, deactivation of renin-angiotensin-aldosterone system, ketone body formation, alterations in energy homeostasis, glycosuria, lipolysis, anti‐inflammatory, and antioxidative actions. history main article: discovery and development of gliflozins phlorizin is a molecule with sglt inhibiting properties, and served an important role in the development of the gliflozin class of medications.