Effects of a long-acting GLP-1 mimetic (PF-04603629) on pulse rate and diastolic blood pressure in patients with type 2 diabetes mellitus

Gustavson, Stephanie M.; Chen, D.; Somayaji, Veena; Hudson, Krischan J; Baltrukonis, Daniel; Singh, Jaya; Boyden, Tracey; Calle, Roberto A.

doi:10.1111/j.1463-1326.2011.01479.x

Cited by 19 publications

(15 citation statements)

References 12 publications

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“…Effectively, this is thought to be the mechanism that enables GLP‐1 RAs to lower energy intake, thereby reducing body weight, although to a varying degree. The increase in pulse rate reported with semaglutide treatment has also been previously reported in, for example, liraglutide‐ and exenatide‐treated participants, although the potential mechanisms behind this haemodynamic effect are unclear …”

Section: Discussionmentioning

confidence: 54%

Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy inJapanese people with type 2 diabetes

Seino

Terauchi

Osonoi

et al. 2017

Diabetes Obesity Metabolism

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AimsTo assess the safety and efficacy of monotherapy with once‐weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).MethodsIn this phase IIIa randomized, open‐label, parallel‐group, active‐controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run‐in period) received once‐weekly s.c. semaglutide (0.5 or 1.0 mg) or once‐daily oral sitagliptin 100 mg. The primary endpoint was number of treatment‐emergent adverse events (TEAEs) after 30 weeks.ResultsOverall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide‐ vs sitagliptin‐treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin −1.13%, 95% confidence interval [CI] −1.32; −0.94, and −1.44%, 95% CI −1.63; −1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD −2.22 kg, 95% CI −3.02; −1.42 and −3.88 kg, 95% CI −4.70; −3.07; both P < .0001).ConclusionsIn Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon‐like peptide‐1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

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Section: Discussionmentioning

confidence: 54%

Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy inJapanese people with type 2 diabetes

Seino

Terauchi

Osonoi

et al. 2017

Diabetes Obesity Metabolism

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“…20 A more recently published study of the longacting GLP-1 agent PF-04603629 reported a substantial rise in the heart rate (a mean increase of 23 bpm at 24 h after injection of the higher dose studied), together with a rise in the diastolic blood pressure. 21 While there is no evidence to date that these agents (short-acting or long-acting) increase cardiovascular event rates, safety data are limited by short follow-up duration. 22 A longer term follow-up is underway but will take a number of years to complete.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis

et al. 2013

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ObjectivesTo synthesise current evidence for the effects of exenatide and liraglutide on heart rate, blood pressure and body weight.DesignMeta-analysis of available data from randomised controlled trials comparing Glucagon-like peptide-1 (GLP-1) analogues with placebo, active antidiabetic drug therapy or lifestyle intervention.ParticipantsPatients with type 2 diabetes.Outcome measuresWeighted mean differences between trial arms for changes in heart rate, blood pressure and body weight, after a minimum of 12-week follow-up.Results32 trials were included. Overall, GLP-1 agonists increased the heart rate by 1.86 beats/min (bpm) (95% CI 0.85 to 2.87) versus placebo and 1.90 bpm (1.30 to 2.50) versus active control. This effect was more evident for liraglutide and exenatide long-acting release than for exenatide twice daily. GLP-1 agonists decreased systolic blood pressure by −1.79 mm Hg (−2.94 to −0.64) and −2.39 mm Hg (−3.35 to −1.42) compared to placebo and active control, respectively. Reduction in diastolic blood pressure failed to reach statistical significance (−0.54 mm Hg (−1.15 to 0.07) vs placebo and −0.50 mm Hg (−1.24 to 0.24) vs active control). Body weight decreased by −3.31 kg (−4.05 to −2.57) compared to active control, but by only −1.22 kg (−1.51 to −0.93) compared to placebo.ConclusionsGLP-1 analogues are associated with a small increase in heart rate and modest reductions in body weight and blood pressure. Mechanisms underlying the rise in heart rate require further investigation.

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“…In humans (2,7,9,10,24,26,27,38,43), GLP-1 has a modest acute impact on hemodynamics. In most reports (2,26,27,38,43), the studies have not been designed to elucidate primarily hemodynamic effects of GLP-1; however, even when hemodynamics were measured continuously, the results were ambiguous.…”

mentioning

confidence: 99%

Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy

Asmar

Simonsen

Asmar

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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-During acute administration of native glucagon-like peptide-1 (GLP-1), we previously demonstrated central hemodynamic effects in healthy males, whereas renal hemodynamics, despite renal uptake of GLP-1 in excess of glomerular filtration, was unaffected. In the present study, we studied hemodynamic effects of GLP-1 in patients with type 2 diabetes under fixed sodium intake. During a 3-h infusion of GLP-1 (1.5 pmol·kg Ϫ1 ·min Ϫ1 ) or saline, intra-arterial blood pressure and heart rate were measured continuously, concomitantly with cardiac output estimated by pulse contour analysis. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured using Fick's Principle after catheterization of a renal vein. Urine collection was conducted throughout the experiments at voluntary voiding, and patients remained supine during the experiments. During the GLP-1 infusion, systolic and diastolic blood pressure and cardiac output remained unchanged, whereas heart rate increased significantly. Arterio-venous gradients for GLP-1 exceeded glomerular filtrations significantly, but renal plasma flow and glomerular filtration rate as well as renal sodium and lithium excretion were not affected. In conclusion, acute administration of GLP-1 in patients with type 2 diabetes leads to a positive chronotropic effect, but in contrast to healthy individuals, cardiac output does not increase in patients with type 2 diabetes. Renal hemodynamics and sodium excretion are not affected.glucagon-like peptide-1; blood pressure; heart rate; cardiac output; renal plasma flow; glomerular filtration rate; renal sodium excretion IN ADDITION TO THE GLUCOREGULATORY ACTIONS of glucagon-like peptide-1 (GLP-1) (11), it has been shown to have acute hemodynamic effects. In otherwise healthy rodents, several studies (36) have demonstrated dose-dependent relationships between GLP-1 concentrations and elevations in blood pressure and heart rate. Both central and peripheral factors seem to contribute to GLP-1-mediated pressor and chronotropic responses. However, in salt-sensitive rats and hypertensive mice, GLP-1 has antihypertensive effects due to substantial diuretic and natriuretic effects (37). Moreover, in nondiabetic rodents, GLP-1 directly induces remarkable increases in renal plasma flow (RPF) and glomerular filtration rate (37) via preglomerular dilation (15).

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Effects of a long-acting GLP-1 mimetic (PF-04603629) on pulse rate and diastolic blood pressure in patients with type 2 diabetes mellitus

Cited by 19 publications

References 12 publications

Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy inJapanese people with type 2 diabetes

Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy inJapanese people with type 2 diabetes

Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis

Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy

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