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Abstract-Glucagon-like peptide-1 receptor agonists, used to treat type 2 diabetes mellitus, are associated with small reductions in systolic blood pressure (SBP) and increases in heart rate. However, findings based on clinic measurements do not adequately assess a drug's 24-hour pharmacodynamic profile. The effects of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, on BP and heart rate were investigated using ambulatory BP monitoring. Patients (n=755; 56±10 years; 81% white; 48% women), with type 2 diabetes mellitus, taking ≥1 oral antihyperglycemic medication, with a clinic BP between 90/60 and 140/90 mm Hg were randomized to dulaglutide (1.5 or 0.75 mg) or placebo subcutaneously for 26 weeks. Ambulatory BP monitoring was performed at baseline and at 4, 16, and 26 weeks. The primary end point was change from baseline to week 16 in mean 24-hour SBP, a tree gatekeeping strategy compared the effects of dulaglutide to placebo. Both doses of dulaglutide were noninferior to placebo for changes in 24-hour SBP and diastolic blood pressure, and dulaglutide 1. 5,6 and has been shown to reduce body weight in many subjects. 6 The present study (NCT01149421) investigated the effects of dulaglutide on BP and HR during 26 weeks using 24-hour ambulatory blood pressure monitoring (ABPM) in patients with T2DM. Methods Study DesignThe study was a randomized, double-blind, multicenter, placebo-controlled, 26-week trial designed to evaluate the effects of dulaglutide when compared with placebo on BP and HR in patients with T2DM with or without hypertension and BP<140/90 mm Hg. After a 2-week placebo screening and run-in period, eligible patients were randomly assigned using a computer-generated random sequence to injectable placebo or 1.5 or 0.75 mg of dulaglutide (1:1:1) once weekly for 26 weeks and followed up for an additional 4-week off-therapy. Study visits occurred approximately every 4 weeks through 16 weeks, and then at 26 weeks with interim phone follow-up. Randomization was stratified by site and hypertension status (previous diagnosis and the use of antihypertensive medications or a new diagnosis if SBP≥130 mm Hg or DBP ≥80 mm Hg on ≥2 separate days 7 versus normotensive). PopulationPatients were recruited from 76 centers in Argentina, Brazil, Canada, Czech Republic, Denmark, India, Puerto Rico, and the United States. Men and women ≥18 years of age with T2DM, a glycated hemoglobin A1c ≥7.0% and ≤9.5%, on ≥1 oral antihyperglycemic medication for ≥1 month (≥3 months if taking a thiazolidinedione), body mass index ≥23 kg/m 2 , and a stable body weight (±5% for ≥3 months), were included. Mean seated BP was required to be between >90/60 and <140/90 mm Hg, and patients with hypertension had to be taking ≤3 classes of antihypertensive medications (same regimen, ≥1 month). Exclusion criteria were a recent (<3 months) major cardiovascular event, mean seated HR<60 or >100 bpm, history of tachyarrhythmia, pancreatitis, clinically significant hepatic disease, renal impairment (estimated glomerular filtration r...

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Insulin lispro, an insulin analog recently developed particularly for mealtime therapy, has a fast absorption rate and a short duration of action. We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM. The study was a 6-month randomized multinational (17 countries) and multicenter (102 investigators) clinical trial performed with an open-label crossover design. Insulin lispro was injected immediately before the meal, and regular human insulin was injected 30-45 min before the meal. Throughout the study, the postprandial rise in serum glucose was significantly lower during insulin lispro therapy. At the endpoint, the postprandial rise in serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in patients treated with insulin lispro (P < 0.001). The rate of hypoglycemia was 12% less with insulin lispro (6.4 +/- 0.2 vs. 7.2 +/- 0.3 episodes/30 days, P < 0.001), independent of basal insulin regimen or HbA1c level. The reduction was observed equally in episodes with and without symptoms. When the total number of episodes for each patient was analyzed according to the time of occurrence, the number of hypoglycemic episodes was less with insulin lispro than with regular human insulin therapy during three of four quarters of the day (P < 0.001). The largest relative improvement was observed at night. In conclusion, insulin lispro improves postprandial control, reduces hypoglycemic episodes, and improves patient convenience, compared with regular human insulin, in IDDM patients.

In prepubertal children, insulin lispro given before meals is safe and significantly lowers postprandial glucose levels after breakfast and dinner compared with regular human insulin, and insulin lispro given after the meal provides similar benefits as regular human insulin before the meal.