Pramlintide, the synthetic analogue of amylin: physiology, pathophysiology, and effects on glycemic control, body weight, and selected biomarkers of vascular risk

Pramlintide is a synthetic version of the naturally occurring pancreatic peptide called amylin. Amylin and pramlintide have similar effects on lowering postprandial glucose, lowering postprandial glucagon and delaying gastric emptying. Pramlintide use in type 1 and insulin requiring type 2 diabetes mellitus (DM) is associated with modest reductions in HbA1c often accompanied by weight loss. Limited data show a neutral effect on blood pressure. Small studies suggest small reductions in LDL-cholesterol in type 2 DM and modest reductions in triglycerides in type 1 DM. Markers of oxidation are also reduced in conjunction with reductions in postprandial glucose. Nausea is the most common side effect. These data indicate that pramlintide has a role in glycemic control of both type 1 and type 2 DM. Pramlintide use is associated with favorable effects on weight, lipids and other biomarkers for atherosclerotic disease

Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes

It is important for patients that treatments for diabetes not increase cardiovascular (CV) risk. The objective of this analysis was to examine retrospectively the CV safety of exenatide BID, a GLP-1 receptor agonist approved for treating hyperglycemia in patients with type 2 diabetes not adequately controlled with diet and exercise. Individual participant data was pooled to assess the relative risk (RR) of CV events with exenatide BID versus a pooled comparator (PC) group treated with either placebo or insulin from 12 controlled, randomized, clinical trials ranging from 12-52 weeks. Mean baseline values for HbA1c (8.33-8.38%), BMI (31.3-31.5 kg/m2), and duration of diabetes (8 y) were similar between groups. Trials included patients with histories of microvascular and/or macrovascular disease. Customized primary major adverse CV events (MACE) included stroke, myocardial infarction, cardiac mortality, acute coronary syndrome, and revascularization procedures. The Primary MACE RR (0.7; 95% CI 0.38, 1.31), calculated by the Mantel-Haenszel method (stratified by study), suggested that exenatide use (vs. PC) did not increase CV risk; this result was consistent across multiple analytic methods. Because the trials were not designed to assess CV outcomes, events were identified retrospectively from a list of preferred terms by physicians blinded to treatment. Other limitations included the low number of CV events, the short duration of trials (≤1 y), and a single active comparator (insulin). The results of these analyses are consistent with those of a recent retrospective analysis of a large insurance database that found that patients treated with exenatide twice daily were less likely to have a CV event than were patients treated with other glucose-lowering therapies

Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study

<p>Abstract</p> <p>Background</p> <p>Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate (HR) and blood pressure (BP) in subjects with type 2 diabetes mellitus (T2DM).</p> <p>Methods</p> <p>In this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 μg for 4 weeks followed by 10 μg) or placebo BID for 12 weeks. Heart rate and BP were assessed with 24-hour ambulatory BP monitoring. The primary measure was change from baseline in mean 24-hour HR.</p> <p>Results</p> <p>Fifty-four subjects (28 exenatide, 26 placebo) were randomized and comprised the intent-to-treat population. Baseline values (exenatide and placebo) were (mean ± SE) 74.4 ± 2.1 and 74.5 ± 1.9 beats/minute for HR, 126.4 ± 3.2 and 119.9 ± 2.8 mm Hg for systolic BP (SBP), and 75.2 ± 2.1 and 70.5 ± 2.0 mm Hg for diastolic BP (DBP). At 12 weeks, no significant change from baseline in 24-hour HR was observed with exenatide or placebo (LS mean ± SE, 2.1 ± 1.4 versus -0.7 ± 1.4 beats/minute, respectively; between treatments, p = 0.16). Exenatide therapy was associated with trends toward lower 24-hour, daytime, and nighttime SBP; changes in DBP were similar between groups. No changes in daytime or nighttime rate pressure product were observed. With exenatide, body weight decreased from baseline by -1.8 ± 0.4 kg (p < 0.0001; treatment difference -1.5 ± 0.6 kg, p < 0.05). The most frequently reported adverse event with exenatide was mild to moderate nausea.</p> <p>Conclusions</p> <p>Exenatide demonstrated no clinically meaningful effects on HR over 12 weeks of treatment in subjects with T2DM. The observed trends toward lower SBP with exenatide warrant future investigation.</p> <p>Trial registration</p> <p>NCT00516074</p

The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study

Objective To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

Mean percent changes in lipid values in 203 type 2 diabetic patients on placebo and 3 different doses of pramlintide for 4 weeks

Derived from .<p><b>Copyright information:</b></p><p>Taken from "Pramlintide, the synthetic analogue of amylin: physiology, pathophysiology, and effects on glycemic control, body weight, and selected biomarkers of vascular risk"</p><p></p><p>Vascular Health and Risk Management 2008;4(2):355-362.</p><p>Published online Jan 2008</p><p>PMCID:PMC2496974.</p><p>© 2008 Dove Medical Press Limited. All rights reserved</p