A quick guide to the SUSTAIN trials
There are a confusing number of SUSTAIN phase III trials either completed or in process, investigating the once-weekly injectable glucagon-like peptide-1 analog semaglutide in patients with type 2 diabetes. The trials are all sponsored by the drug-maker, Novo Nordisk.
Here is our guide to the 10 trials launched to date, which are complete, and which have so far been published in a peer-reviewed journal.
SUSTAIN 1: published
|Patient population: type 2 diabetes||Comparator treatment: placebo|
The SUSTAIN 1 findings were published in The Lancet Diabetes & Endocrinology in January 2017. They showed that, during 30 weeks of treatment, patients given semaglutide had significantly larger reductions in glycated hemoglobin and in bodyweight than those given placebo.
Related news story: SUSTAIN 1: ‘high degree’ of glycemic control with semaglutide in type 2 diabetes
SUSTAIN 2: published
|Patient population: type 2 diabetes, taking metformin and/or thiazolidinediones||Comparator treatment: sitagliptin|
SUSTAIN 2, also published in The Lancet Diabetes & Endocrinology, in April 2017, was a head-to-head study of weekly injectable semaglutide versus daily oral sitagliptin in patients already taking metformin and/or thiazolidinediones.
The findings showed significantly larger reductions in HbA1c with semaglutide, as well as larger reductions in bodyweight.
Related news story: SUSTAIN 2 shows better glycemic control with semaglutide than sitagliptin
SUSTAIN 3: completed, not yet published
|Patient population: type 2 diabetes, taking metformin and/or thiazolidinedione and sulfonylureas||Comparator treatment: extended-release exenatide|
Novo Nordisk announced in September 2015 that SUSTAIN 3 had met its primary endpoint, with significantly larger HbA1c reductions among patients assigned to receive semaglutide than exenatide during 52 weeks of treatment.
SUSTAIN 4: published
|Patient population: type 2 diabetes; insulin-naïve, taking metformin with/without sulfonylurea||Comparator treatment: insulin glargine|
SUSTAIN 4, again published in The Lancet Diabetes & Endocrinology, pitted semaglutide against insulin during 30 weeks of treatment. The trial met the noninferiority endpoint and, in fact, patients achieved significantly larger HbA1c reductions with semaglutide than insulin, although the researchers noted that insulin titration may not have been optimal.
Related news story: SUSTAIN 4: weekly semaglutide a good option after metformin failure
SUSTAIN 5: completed, not yet published
|Patient population: type 2 diabetes, taking basal insulin with/without metformin||Comparator treatment: placebo|
Although not yet published, the SUSTAIN 5 investigators announced at EASD 2016 that semaglutide had proved significantly more effective than placebo for reducing HbA1c levels and bodyweight in patients taking basal insulin during 30 weeks of treatment.
SUSTAIN 6: published
|Patient population: type 2 diabetes at high cardiovascular risk, excluding those using other GLP-1 analogs or dipeptidyl peptidase 4 inhibitors||Comparator treatment: placebo|
The results of SUSTAIN 6, published in The New England Journal of Medicine, showed a significant 26% reduction in the composite primary endpoint of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. This endpoint occurred in 6.6% of patients taking semaglutide and 8.9% of those taking placebo during a median of 2.1 years of follow-up.
Related news story: Favourable cardiovascular safety profile for semaglutide
SUSTAIN 9: currently recruiting
|Patient population: type 2 diabetes, taking sodium glucose co-transporter-2 inhibitor with or without metformin or sulfonylurea||Comparator treatment: placebo|
Whereas the initial SUSTAIN trials tested semaglutide 0.5 and 1.0 mg, this one is restricted to the higher dose, which produced the best results in the earlier studies. It will be tested against placebo as an add-on to sodium glucose co-transporter-2 inhibitor treatment over 30 weeks in an estimated 300 patients.
SUSTAIN - CHINA MRCT: not yet recruiting
|Patient population: patients with type 2 diabetes, taking metformin||Comparator treatment: sitagliptin|
Similar to SUSTAIN 2, this trial will test semaglutide 0.5 and 1.0 mg against sitagliptin, but in a patient population drawn from China, Hong Kong, Brazil, Taiwan, Ukraine, South Korea, and South Africa. The investigators hope to have collected all data for the primary analysis by the end of September 2018.
SUSTAIN (Japan): completed, not yet published
|Patient population: Japanese type 2 diabetes patients on stable oral antidiabetic medication||Comparator treatment: oral antidiabetic, selected according to baseline medication|
Patients in this trial remained on their baseline treatment and were randomly assigned to receive either semaglutide (0.5 or 1.0 mg) or investigators’ choice of oral antidiabetic agent.
SUSTAIN (Japan, sitagliptin): completed, not yet published
|Patient population: Japanese patients with type 2 diabetes on stable oral antidiabetic monotherapy||Comparator treatment: sitagliptin|
This trial is similar to SUSTAIN 2, but conducted in Japanese patients on monotherapy “at a half-maximum dose or below.” No results have yet been announced; Novo Nordisk has filed for regulatory approval of semaglutide in Japan, but this application is based on results from “across the SUSTAIN programme.”