Many type 2 diabetes patients require mealtime insulin to help maintain glycemic control, but this carries a risk of hypoglycemia. Since the glucose-lowering mechanism of SGLT2 inhibitors does not require beta-cell function, we asked if addition of the SGLT2 inhibitor canagliflozin (CANA) could “rescue” patients from the need for mealtime insulin. In a pilot study, after 2 week run-in, 26 pts requiring QID basal-bolus insulin with negative GAD antibodies were randomized, double-blind, to CANA or placebo (PLBO); dosage was 100 mg/d for 2 week, then 300 mg/d for 22 week. At baseline, the groups were similar: mean age 64 year, BMI 31.2, 100% male, 64% black, HbA1c 8.0%, insulin 107 units/day, CGM time in range (TIR, 70-180 mg/dl) 75.5%, hypoglycemia (<54 mg/dl) 0.41%, and hyperglycemia (>180 mg/dl) 22.8% (all p>0.05). Over 24 weeks, insulin was adjusted weekly in all pts to improve control but avoid hypoglycemia. One PLBO pt had a penile infection and d/c’d study drug, but other adverse events were similar, and there was no severe hypoglycemia. Among 13 CANA and 11 PLBO pts who followed the protocol for 24 week, during the last 12 week, despite a 27% reduction in insulin dosage to 78 units/day with CANA vs. a 7% increase to 112 units/day with PLBO (p=ns), 37% of CANA pts were able to d/c mealtime Rx entirely, and 4% to switch to glipizide, for >1 meal/day, vs. 32% and 8% with PLBO, respectively (p=ns); CGM metrics were better with CANA as well, TIR 79% vs. 74%, hypoglycemia 0.58% vs. 0.84%, and hyperglycemia 18.7% vs. 23.9% with CANA vs. PLBO, respectively, all p=ns, and HbA1c was 7.4% with CANA vs. 7.6% with PLBO (p=ns).

Conclusions: Addition of canagliflozin to the regimens of patients using basal-bolus insulin, allows some patients to discontinue mealtime medication entirely, and others to switch from insulin to an oral agent, for at least one meal/day, with concomitant improvement in glycemic control, although differences from placebo were not statistically significant in this pilot study. Intensive management allows many patients to reduce their need for mealtime insulin.


L.S. Phillips: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AbbVie Inc., GlaxoSmithKline plc., Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. Stock/Shareholder; Self; Diasyst Inc. Other Relationship; Self; Diasyst Inc., Janssen Pharmaceuticals, Inc. F. Morehead: None. L.P. Savoye: None. M.K. Rhee: None. D. Olson: None. E.H. Burgess: None. X. Cui: None. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. R. Bailey: None.


U.S. Department of Veterans Affairs; National Institutes of Health

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