Canagliflozin (CANA), a Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor, Improves Glycemia and is Well Tolerated in Type 2 Diabetes Mellitus (T2DM) Subjects With Moderate Renal Impairment

SGLT2 Inhibitors to Control Glycemia in Type 2 Diabetes Mellitus: A New Approach to an Old Problem

“…15 Lower rates of UGE have been seen with ipragliflozin 59 and dapagliflozin 60 use in patients with renal impairment compared with patients with normal renal function. Clinical trials of SGLT2 inhibitors in patients with T2DM and renal impairment have shown mixed results on HbA 1c level lowering, 60,61 and further data are needed to establish the efficacy of these agents in these patients. Currently, 2 SGLT2 inhibitors have been approved for clinical use by regulatory authorities.…”

“…31,47 The SGLT2 inhibitors have consistently have been associated with patient weight loss in phase II-III clinical trials when used as monotherapy or as an add-on to metformin, sulfonylurea, or insulin. 25,26,[32][33][34][35][36][37][38][39][40][41][42][43][45][46][47][48][50][51][52][53][54][56][57][58]61 Weight reductions of # 4.7 kg have been reported during study periods ranging from 4 to 90 weeks. In addition, when used in combination with pioglitazone, dapagliflozin reduces the drug-associated weight gain seen in patients treated with pioglitazone.…”

Sodium glucose cotransporter 2 and the diabetic kidney

“…However, in a 52-week placebo-controlled trial in patients with moderate renal dysfunction (GFR >30 and <60), this initial drop remains stable without correction during the duration of treatment, although there was improvement in albuminuria [43]. In a 26 week, phase III placebo-controlled trial in patients with moderate renal dysfunction, canagliflozin at varying doses showed mild worsening of creatinine levels (9 and 10% vs. 4%), although the albumin creatinine ratio (ACR) and HbA1c showed improvement [44]. Finally, dapagliflozin has been reported to be less effective in lowering HbA1c in patients with a reduction in renal function, as might be expected given that the effect of the drug requires ample GFR [43].…”

Canagliflozin

“…Reference: Yale JF, et al, 2013 16,17 Percentage change in LDL-C from baseline: 9.6% with the 100 mg dose and 114.1% with the 300 mg dose compared with 15% with glimepiride. Other Endpoint(s): The overall incidence of adverse events did not differ between groups; however, the canagliflozin-treated patients experienced a higher incidence of genital fungal infections (14.3% with canagliflozin 100 mg and 23.8% with canagliflozin 300 mg vs 3.7% with glimepiride in women; 6.7% and 8.3% vs 1.1%, respectively, in men), UTIs (6.4% with both doses of canagliflozin vs 4.4% with glimepiride), and osmotic diuresis-related adverse events (all less than 3%).…”

“…1 Up to 24% of women who received canagliflozin in clinical trials developed a genital fungal infection. 17,18,19,24 Most infections were treated with topical or oral antifungals and resolved without study drug interruption. 22 Hypersensitivity reactions (eg, generalized urticaria), mild to serious in degree, generally occurred within hours to days after initiating canagliflozin treatment.…”