Treatment with the glucagon receptor antagonist LY2409021 increases ambulatory blood pressure in patients with type 2 diabetes

Aims To assess the effect of LY2409021 on systolic blood pressure ( SBP ) in patients with type 2 diabetes. Materials and methods This 6‐week, randomized, crossover study evaluated the effects of once‐daily administration of LY2409021 20 mg vs those of placebo on SBP , diastolic BP ( DBP ), and mean arterial pressure ( MAP ) using 24‐hour ambulatory BP monitoring ( ABPM ) in 270 subjects treated with diet/exercise ± metformin. Other measures included changes in glycemic control, serum lipids, and hepatic safety markers. Results At 6 weeks of LY2409021 treatment, 24‐hour mean SBP was increased, with a least squares mean ( LSM ) difference of 2.26 mm H g vs placebo (95% CI : 1.11, 3.40; P  < .001). The 24‐hour mean DBP and MAP also increased, with LSM differences of 1.37 mm H g (95% CI : 0.66, 2.08; P  < .001) and 1.67 mm H g (95% CI : 0.86, 2.47; P  < .001) vs placebo, respectively. At week 6, LY2409021 treatment reduced glycated hemoglobin ( HbA1c ) levels, with an LSM difference of −0.49% (−5.4 mmol/mol) (95% CI : −0.56%, −0.42% [−6.1, −4.6 mmol/mol]; P  < .001) vs placebo. Mean HbA1c at baseline was 7.3% (56 mmol/mol). Small but significant changes in serum lipid and aminotransferase levels were observed with LY2409021 treatment (all P  < .05 vs placebo). Conclusions Statistically significant increases in BP , MAP and serum lipid levels were observed with LY2409021 treatment at a dose that lowered HbA1c and glucose levels. These effects may limit the clinical utility of LY2409021 as a chronic treatment for type 2 diabetes.