Current study in Lancet showed that patients reduced their A1c levels by 1.55%
Despite a broad range of pharmacological options for the treatment of type 2 diabetes, optimum glycemic 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. Compared to placebo, semaglutide monotherapy provided glycemic control and weight loss in patients with type 2 diabetes in a multinational trial.
Dr. Christopher Sorli of Billings Clinic Research Center, Montana, examined the performance of semaglutide in this role, and enrolled treatment-naive patients for whom diet and exercise alone had been the only intervention for at least 30 days.
388 patients were randomly assigned to once-weekly subcutaneous semaglutide (0.5 mg or 1.0 mg), or volume-matched placebo. Their mean baseline HbA1c was 8.05% and their mean body weight was 91.93 kg. At week 30, HbA1c significantly decreased by 1.45% with 0.5 mg semaglutide and by 1.55% with 1.0 mg. With placebo, there was a non-significant reduction of 0.02%.
Also at week 30, body weight significantly decreased by 3.73 kg with 0.5 mg semaglutide and by 4.53 kg with 1.0 mg. There was a non-significant decrease of 0.98 kg with placebo.
In all groups, adverse events were mild or moderate and gastrointestinal effects were the most common. Nausea was reported by 20% of the 0.5 mg semaglutide group, 24% of the 1.0 mg group and 8% of the placebo patients. Corresponding proportions for diarrhea were 13%, 11% and 2%.
They did a double-blind, randomized, parallel-group, placebo-controlled phase 3a trial (SUSTAIN 1) at 72 sites over 8 countries. Eligible participants were treatment-naive individuals aged 18 years or older 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% (53–86 mmol/mol). They randomly assigned participants 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. 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.
Between February 3, 2014, and August 21, 2014, they 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 Mean baseline bodyweight was 91.93 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. 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 diarrhea 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.
From the results of the study, it was concluded that 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.
Results from a much larger trial of semaglutide, SUSTAIN-6, in 3,200 patients with type 2 diabetes at high cardiovascular risk, from 22 countries, were presented at the EASD meeting in Munich last year. These results showed that patients using the once-weekly subcutaneous semaglutide had a significant 26% lower risk for the primary composite outcome of first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke over two years compared with those receiving placebo.
Head-to-head comparison studies are ongoing between GLP-1 and SGLT-2 inhibitors, and the results will probably be announced at this year’s ADA 77th scientific session in June.
Novo Nordisk has submitted a New Drug Application to the U.S. Food and Drug Administration for once-weekly semaglutide for the treatment of adults with type 2 diabetes.
- HbA1c significantly decreased by 1.45% with 0.5 mg semaglutide and by 1.55% with 1.0 mg.
- Weight significantly decreased by 3.73 kg with 0.5 mg semaglutide and by 4.53 kg with 1.0 mg.
- Results from a much larger study also showed a drop by 26% of first occurrence of cardiovascular death, nonfatal myocardial infarction), or nonfatal stroke over 2 years.