OBJECTIVE: Evaluate the safety and efficacy of RVT-1502, a novel oral glucagon receptor antagonist, in subjects with type 2 diabetes inadequately controlled onmetformin. RESEARCH DESIGN AND METHODS: In a phase 2, double-blind, randomized, placebo-controlled study, subjects with type 2 diabetes (n = 166) on a stable dose ofmetformin were randomized (1:1:1:1) to placebo or RVT-1502 5, 10, or 15 mg once daily for 12 weeks. The primary end point was change from baseline in HbA1c for each dose of RVT-1502 compared with placebo. Secondary end points included change from baseline in fasting plasma glucose (FPG) and safety assessments. RESULTS: Over 12 weeks, RVT-1502 significantly reduced HbA1c relative to placebo by 0.74%, 0.76%, and 1.05% in the 5-, 10-, and 15-mg groups (P < 0.001), respectively, and FPG decreased by 2.1, 2.2, and 2.6 mmol/L (P < 0.001). The proportions of subjects achieving an HbA1c <7.0% were 19.5%, 39.5%, 39.5%, and 45.0% with placebo and RVT-1502 5, 10, and 15 mg (P ≤ 0.02 vs. placebo). The frequency of hypoglycemia was low, and no episodes were severe. Mild increases in mean aminotransferase levels remaining below the upper limit of normal were observed with RVT-1502 but were reversible and did not appear to be dose related, with no other liver parameter changes. Weight and lipid changes were similar between RVT-1502 and placebo. RVT-1502-associated mild increases in blood pressure were not dose related or consistent across time. CONCLUSIONS: Glucagon receptor antagonism with RVT-1502 significantly lowers HbA1c and FPG, with a safety profile that supports further clinical development with longer-duration studies (NCT02851849).
RCT Entities:
OBJECTIVE: Evaluate the safety and efficacy of RVT-1502, a novel oral glucagon receptor antagonist, in subjects with type 2 diabetes inadequately controlled on metformin. RESEARCH DESIGN AND METHODS: In a phase 2, double-blind, randomized, placebo-controlled study, subjects with type 2 diabetes (n = 166) on a stable dose of metformin were randomized (1:1:1:1) to placebo or RVT-1502 5, 10, or 15 mg once daily for 12 weeks. The primary end point was change from baseline in HbA1c for each dose of RVT-1502 compared with placebo. Secondary end points included change from baseline in fasting plasma glucose (FPG) and safety assessments. RESULTS: Over 12 weeks, RVT-1502 significantly reduced HbA1c relative to placebo by 0.74%, 0.76%, and 1.05% in the 5-, 10-, and 15-mg groups (P < 0.001), respectively, and FPG decreased by 2.1, 2.2, and 2.6 mmol/L (P < 0.001). The proportions of subjects achieving an HbA1c <7.0% were 19.5%, 39.5%, 39.5%, and 45.0% with placebo and RVT-1502 5, 10, and 15 mg (P ≤ 0.02 vs. placebo). The frequency of hypoglycemia was low, and no episodes were severe. Mild increases in mean aminotransferase levels remaining below the upper limit of normal were observed with RVT-1502 but were reversible and did not appear to be dose related, with no other liver parameter changes. Weight and lipid changes were similar between RVT-1502 and placebo. RVT-1502-associated mild increases in blood pressure were not dose related or consistent across time. CONCLUSIONS:Glucagon receptor antagonism with RVT-1502 significantly lowers HbA1c and FPG, with a safety profile that supports further clinical development with longer-duration studies (NCT02851849).
Authors: Ryan A Lafferty; Laura M McShane; Zara J Franklin; Peter R Flatt; Finbarr P M O'Harte; Nigel Irwin Journal: J Endocrinol Date: 2022-09-14 Impact factor: 4.669
Authors: Ryan A Lafferty; Finbarr P M O'Harte; Nigel Irwin; Victor A Gault; Peter R Flatt Journal: Front Endocrinol (Lausanne) Date: 2021-05-18 Impact factor: 5.555
Authors: Kleopatra Alexiadou; Joyceline Cuenco; James Howard; Nicolai Jacob Wewer Albrechtsen; Ibiyemi Ilesanmi; Anna Kamocka; George Tharakan; Preeshila Behary; Paul R Bech; Ahmed R Ahmed; Sanjay Purkayastha; Robert Wheller; Matthieu Fleuret; Jens Juul Holst; Stephen R Bloom; Bernard Khoo; Tricia M-M Tan Journal: BMJ Open Diabetes Res Care Date: 2020-03