This study evaluated the effect of ZT-01 on glucagon counterregulation during hypoglycemia in adults with type 1 diabetes, in a Phase 1b randomized, three-arm, double-blind crossover trial in 23 hypoglycemia aware adults with T1D. Participants underwent three hypoglycemic clamp procedures with 3 or 20 mg ZT-01 or placebo dosed 1 h prior to stepwise glucose clamp conditions using variable rate IV insulin infusion: euglycemia (5.0 ± 0.5 mmol/L), level 1 (3.5 ± 0.3 mmol/L, L1), and level 2 hypoglycemia (2.6 ± 0.2 mmol/L, L2).

With ZT-01, peak glucagon increased by up to 15.1 ± 10.5 and 27.1 ± 17.3 pg/mL, in L1 and L2 hypoglycemia, respectively, compared with no increase in L1 and an 8.4 ± 8.4 pg/mL increase in L2 hypoglycemia with placebo (p<0.0001, figure). A counterregulatory response of increased glucose level coinciding with an increased glucagon level was observed more frequently with ZT-01 than placebo. No clinically significant effects on other counterregulatory hormones or hypoglycemia symptom scores were observed with ZT-01. A transient rise in glucagon and blood glucose was observed with ZT-01 post-dose prior to hypoglycemia. No SAEs were reported and no TEAEs were observed with ZT-01.

This study demonstrates proof-of-concept that ZT-01 significantly enhances the defective counterregulatory response in people with T1D during L1 and L2 hypoglycemia.


A.Abitbol: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Dexcom, Inc., Novo Nordisk Canada Inc., Janssen Pharmaceuticals, Inc., Research Support; Abbott Diabetes, Lilly Diabetes, Zucara Therapeutics, Novo Nordisk Canada Inc., Moderna, Inc., Senseonics, Speaker's Bureau; Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Amgen Canada, Dexcom, Inc., Novo Nordisk Canada Inc., HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi. S.Peers: Employee; Zucara Therapeutics. E.Simonson: None. M.Midmer: Board Member; Zucara Therapeutics, Employee; Zucara Therapeutics, Stock/Shareholder; Zucara Therapeutics. M.Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Indigo Diabetes, Consultant; Lilly Diabetes, Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Novo Nordisk, Sanofi, Stock/Shareholder; Supersapiens, Zucara Therapeutics. R.Liggins: Employee; Zucara Therapeutics, Stock/Shareholder; Zucara Therapeutics.

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