• Sun. Dec 5th, 2021

Both drugs reduced FPG to a similar extent


Nov 9, 2021

Both drugs reduced FPG to a similar extent. dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic VER-50589 parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic brokers. Treatment with SGLT2 inhibitors is usually associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a encouraging new treatment option for T2DM. sitagliptin add-on to MET and SU (“type”:”clinical-trial”,”attrs”:”text”:”NCT01137812″,”term_id”:”NCT01137812″NCT01137812) [25]528.1ND?0.37166C167ND?27289C295ND?1888C90ND?2.4Add-on to insulin other antihyperglycemic agents (“type”:”clinical-trial”,”attrs”:”text”:”NCT01032629″,”term_id”:”NCT01032629″NCT01032629) [76]188.2C8.4?0.86?0.89153C158?25?31NDNDND98C102?1.9?2.8Add-on to MET + pioglitazone (“type”:”clinical-trial”,”attrs”:”text”:”NCT01106690″,”term_id”:”NCT01106690″NCT01106690) [77]267.9C8.0?0.62?0.76164C168?29?36NDNDND93C95?2.7%?3.7%Add-on to MET glimepiride add-on to MET(“type”:”clinical-trial”,”attrs”:”text”:”NCT00968812″,”term_id”:”NCT00968812″NCT00968812) [14]527.8?0.01?0.12164C166?6?9NDNDND87?4.4?4.7Add-on to MET sitagliptin add-on to MET (“type”:”clinical-trial”,”attrs”:”text”:”NCT01106677″,”term_id”:”NCT01106677″NCT01106677) [24]527.90?0.15169?9?18NDNDND87?2.4%?2.9% Open in a separate window FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; MET, metformin; ND, not decided; PPG, postprandial glucose; SU, sulfonylurea. When compared with glimepiride as add-on therapy to metformin, canagliflozin 100 mg/d was noninferior to glimepiride and at 300 mg/d was superior to glimepiride in reducing HbA1c after 52 weeks of treatment (Table 1) [14]. The reduction in FPG with canagliflozin was slightly greater than that seen with glimepiride. Body weight decreased with both canagliflozin doses (?3.7 kg [?4.4%] and ?4.0 kg [?4.7%]; glimepiride), whereas there was a small increase (0.7 kg [1.0%]) with glimepiride. In patients receiving background metformin therapy, canagliflozin 100 mg/d for 52 weeks (26-week placebo-and sitagliptin-controlled period followed by a 26-week sitagliptin-controlled period [placebo group switched to sitagliptin]) was noninferior and 300 mg/d was superior to sitagliptin in reducing HbA1c (Table 1) [24]. At week 26, canagliflozin 100 and 300 mg/d significantly reduced HbA1c compared with placebo (?0.79% and ?0.94%, respectively, ?0.17% for placebo; placebo) and in FPG were ?26 and ?28 mg/dL (both placebo) with canagliflozin 100 and 300 mg/d, respectively. More patients receiving canagliflozin achieved HbA1c 7% (48% and 59%, respectively; placebo) than those receiving placebo (28%) [26]. Placebo-corrected imply changes in body weight were ?2.1 and ?2.7 kg for canagliflozin (?0.3 mmHg) and DBP (?2.6 and ?3.5 ?1.4 mmHg). Security In clinical trials, canagliflozin was, in general, well tolerated. Genital infections were more frequent with canagliflozin than with placebo, especially in women (Table 2) [14,24C26,28]. In most studies, osmotic diuresisCrelated adverse events (AEs; e.g. pollakiuria and polyuria) were increased with canagliflozin compared with placebo [14,24C26,28]. Canagliflozin may cause hyperkalemia, especially in patients with moderate renal impairment (eGFR 45 to 60 mL/min/1.73 m2) and in patients taking drugs that affect potassium excretion, such as potassium-sparing diuretics or inhibitors of the reninCangiotensinCaldosterone system [29]. Volume-related AEs (e.g. postural dizziness and orthostasis) were modestly increased with canagliflozin in some studies [26,28]. Small, acute VER-50589 decreases in the eGFR with canagliflozin have been reported VER-50589 in patients with T2DM and normal renal function [14] and in those with CKD [27]. Events of hypoglycemia were infrequent and occurred similarly with canagliflozin and placebo in most studies (Table 2). Hypoglycemia AEs increased when canagliflozin was added to insulin therapy. Table VER-50589 2. Adverse events, including genital infections and urinary tract infections and hypoglycemia,* with canagliflozin in Phase III trials. sitagliptin add-on to MET and SU (“type”:”clinical-trial”,”attrs”:”text”:”NCT01137812″,”term_id”:”NCT01137812″NCT01137812) [25]521 AE78ND77Genital2ND12Urinary6ND4Hypoglycemia41ND43Add-on to insulin other antihyperglycemic brokers (“type”:”clinical-trial”,”attrs”:”text”:”NCT01032629″,”term_id”:”NCT01032629″NCT01032629) [76]181 AE536267Genital31214Urinary154Hypoglycemia254243Add-on to MET + pioglitazone (“type”:”clinical-trial”,”attrs”:”text”:”NCT01106690″,”term_id”:”NCT01106690″NCT01106690) [77]521 AE777076Genital3812Urinary858Hypoglycemia646Add-on to MET glimepiride add-on to MET (“type”:”clinical-trial”,”attrs”:”text”:”NCT00968812″,”term_id”:”NCT00968812″NCT00968812) [14]521 AE696469Genital2911Urinary566Hypoglycemia3465Add-on to MET sitagliptin add-on to MET (“type”:”clinical-trial”,”attrs”:”text”:”NCT01106677″,”term_id”:”NCT01106677″NCT01106677) [24]521 AE677263Genital187Urinary785Hypoglycemia377 Open in a separate windows *Documented hypoglycemia defined by fingerstick or plasma glucose 70 mg/dL, irrespective of symptoms and episodes of severe hypoglycemia necessitating assistance or resulting in seizures or loss of consciousness. AE, adverse event; MET, metformin; ND, not decided; SU, sulfonylurea. PRKD1 Canagliflozin increased low-density lipoprotein cholesterol (LDL-C) by 2% to 12% compared with placebo or comparator and high-density lipoprotein cholesterol (HDL-C) by 1% to 9%. Modest and variable reductions in triglycerides were noted [14,24C26,28]. In a pool of four placebo-controlled trials, canagliflozin increased LDL-C relative to placebo by 4.5% and 8.0% at 100 and 300 mg/d, respectively [18]. Dapagliflozin Dapagliflozin (Farxiga?), a highly selective inhibitor of SGLT2 [21], was approved for the treatment of T2DM in the EU and other countries in 2012 and in the US in 2014. In the US, the recommended starting dose is usually 5 mg once daily, which can be increased to 10 mg VER-50589 once in daily.