Longer Acting GLP-1 Receptor Agonists and the Potential for Improved Cardiovascular Outcomes

A Review of Current Literature

Courtney Aavang Tibble; Tricia Santos Cavaiola; Robert R Henry


Expert Rev Endocrinol Metab. 2013;8(3):247-259. 

In This Article

Semaglutide Weekly Injection

Two abstracts have been published on semaglutide, a new, acylated, LA GLP-1 analogue with a half-life of 160 h. A pharmacokinetic/pharmacodynamic safety and tolerability study showed pharmacokinetic results compatible with once-weekly dosing and an overall treatment effect on FPG, fasting insulin and fasting glucagon. No safety concerns were identified in this study of healthy subjects. All adverse events were considered mild-to-moderate, the most common being nausea, dyspepsia, vomiting, headache and decreased appetite. No hypoglycemia was reported and no treatment effect was observed on calcitonin. The study also showed reduced hunger and prospective food consumption, as well as increased fullness compared with placebo during standard meals on day 2 (but not day 8). In addition, meal energy intake during an ad lib meal appeared reduced at higher doses on both days 2 and 8. There are no statistical data on the aforementioned parameters in regards to food and energy intake. Mean bodyweight decreased in all groups, including placebo, at 4 weeks follow-up.[38]

Another study looked at semaglutide at varying doses versus liraglutide or placebo in Type 2 diabetics in a 12-week, randomized, double-blind, placebo-controlled trial of 411 subjects with a mean A1c of 8.1%.[39] Statistically significant dose-dependent reductions in A1c were seen at all doses of semaglutide ≥0.2 mg as compared with placebo. At higher doses ≥0.8 mg, more subjects reached target A1c <7% than with liraglutide at either 1.2 or 1.8 mg. Bodyweight was also reduced up to 4.8 kg vs placebo 1.2 kg (p < 0.01 for doses ≥ 0.8 mg). Nausea and vomiting were the most frequently cited adverse events. There were few reports of hypoglycemia in the semiglutide (n = 5) and liraglutide (n = 3) groups without episodes of major hypoglycemia. There were no reports of pancreatitis or treatment-related changes in calcitonin.