New GLP-1 Agonist for Diabetes Type II

The long acting GLP-1 agonist, semaglutide, is in phase 3 clinical trial. The current study shows that semaglutide lowers A1c and body weight on average by 1.5% and 9 lbs. It is self-administered once weekly, and available in 0.5 and 1.0 mg doses. Side effects are overall similar to other GLP-1 agonists; primarily gastrointestinal in nature such as nausea and diarrhea.

Previous research, published in NEJM September 2016 showed that semaglutide is safe from the cardiac standpoint when used in patients with type 2 diabetes. Given current positive results and prior CVD safety profile, I anticipate FDA approval in the near future.


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GLP-1 agonists



The Lancet, Diabetes & Endocrinology

Randomized Trial

April 2017


Despite a broad range of pharmacological options for the treatment of type 2 diabetes, optimum glycaemic control remains challenging for many patients and new therapies are necessary. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue in phase 3 development for type 2 diabetes. We assessed the efficacy, safety, and tolerability of semaglutide monotherapy, compared with placebo, in treatment-naive patients with type 2 diabetes who had insufficient glycaemic control with diet and exercise alone.


We did a double-blind, randomised, parallel-group, international, placebo-controlled phase 3a trial (SUSTAIN 1) at 72 sites in Canada, Italy, Japan, Mexico, Russia, South Africa, UK, and USA (including hospitals, clinical research units, and private offices). Eligible participants were treatment-naive individuals >18 years old with type 2 diabetes treated with only diet and exercise alone for at least 30 days before screening, with a baseline HbA1c of 7.0%–10.0%. We randomly assigned participants (2:2:1:1) to either once-weekly subcutaneously injected semaglutide (0.5 mg or 1.0 mg), or volume-matched placebo (0.5 mg or 1.0 mg), for 30 weeks via prefilled PDS290 pen-injectors.

The primary endpoint was the change in mean HbA1c from baseline to week 30, and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30. We assessed efficacy and safety in the modified intention-to-treat population (ie, all participants who were exposed to at least one dose of study drug); both placebo groups were pooled for assessment.


Between February 3, 2014, and August 21, 2014, we randomly assigned 388 participants to treatment; 387 received at least one dose of study medication (128 0.5 mg semaglutide, 130 1.0 mg semaglutide, 129 placebo). 17 (13%) of those assigned to 0.5 mg semaglutide, 16 (12%) assigned to 1.0 mg semaglutide, and 14 (11%) assigned to placebo discontinued treatment; the main reason for discontinuation was gastrointestinal adverse events such as nausea.

Mean baseline HbA1c was 8.05%; at week 30, HbA1c significantly decreased by 1·45% with 0.5 mg semaglutide, significantly decreased by 1.55% with 1.0 mg semaglutide and non-significantly decreased by 0.02% with placebo. Mean baseline bodyweight was 92 kg; at week 30, bodyweight significantly decreased by 3.73 kg  with 0·5 mg semaglutide, significantly decreased by 4·53 kg with 1.0 mg semaglutide, and non-significantly decreased by 0.98 kg with placebo.

No deaths were reported in any of the study groups and most reported adverse events were of mild or moderate severity. The most frequently reported adverse events in both semaglutide groups were gastrointestinal in nature: nausea was reported in 26 (20%) who received 0.5 mg semaglutide, 31 (24%) who received 1.0 mg semaglutide, and 10 (8%) who received placebo, and diarrhoea was reported in 16 (13%) who received 0.5 mg semaglutide, 14 (11%) who received 1.0 mg semaglutide, and three (2%) who received placebo.


Semaglutide significantly improved HbA1c and bodyweight in patients with type 2 diabetes compared with placebo, and showed a similar safety profile to currently available GLP-1 receptor agonists, representing a potential treatment option for such patients.