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 13 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: published
|Patient population: type 2 diabetes, taking metformin and/or thiazolidinedione and sulfonylureas||Comparator treatment: extended-release exenatide|
The SUSTAIN 3 findings, published in Diabetes Care, show that semaglutide 1.0 mg produced a larger HbA1c reduction than exenatide 2.0 mg, of 1.5% versus 0.9% over 56 weeks. However, the researchers cautioned that this could have been influenced by the "more complex device" used to administer exenatide.
Related news story: Semaglutide at least equivalent to exenatide on weekly schedule
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: published
|Patient population: type 2 diabetes, taking basal insulin with/without metformin||Comparator treatment: placebo|
The SUSTAIN 5 findings are published in The Journal of Clinical Endocrinology & Metabolism. They reveal significant 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) reductions in HbA1c during 30 weeks of treatment with 0.5 and 1.0 mg semaglutide, respectively, versus a 0.1% (1.0 mmol/mol) reduction with placebo.
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 7: published
Patient population: type 2 diabetes on stable metformin treatment
Comparator treatment: dulaglutide
The SUSTAIN 7 findings, published in The Lancet Diabetes & Endocrinology, show that semaglutide produced better glycemic control than competitor GLP-1 receptor agonist dulaglutide. The respective average HbA1c reductions were 1.5% versus 1.1% at low doses of 0.5 and 0.75 mg and 1.8% versus 1.4% at high doses of 1.0 and 1.5 mg. Patients taking semaglutide also lost more weight than those taking the equivalent dose of dulaglutide.
Related news story: SUSTAIN 7 published: Semaglutide superior to dulaglutide
SUSTAIN 8: Active, no longer recruiting
Patient population: type 2 diabetes on stable metformin treatment
Comparator treatment: canagliflozin
This trial pits weekly semaglutide against the sodium-glucose cotransporter (SGLT)-2 inhibitor canagliflozin (oral, once daily) in an estimated 784 patients over 52 weeks.
SUSTAIN 9: Active, no longer recruiting
|Patient population: type 2 diabetes, taking SGLT-2 inhibitor with or without metformin or sulfonylurea||Comparator treatment: placebo|
This trial is testing semaglutide against placebo, but this time as an add-on to SGLT-2 inhibitor treatment, over 30 weeks in an estimated 300 patients.
SUSTAIN 10: Active, not longer recruiting
Patient population: type 2 diabetes on stable treatment with up to three oral antidiabetics
Comparator treatment: liraglutide
This trial is a direct comparison of weekly semaglutide and the GLP-1 receptor agonist liraglutide (daily injection) in an estimated 576 patients over 30 weeks. Participants may be taking up to three oral antidiabetic medications from the biguanide, sulfonylurea, and SGLT-2 inhibitor classes.
SUSTAIN - CHINA MRCT: 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): 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 or investigators’ choice of oral antidiabetic agent. The findings published in Diabetes, Obesity and Metabolism show significantly larger reductions in HbA1c with semaglutide 0.5 and 1.0 mg versus other antidiabetics, at 1.7% and 2.0% versus 0.7%, respectively. Patients on semaglutide also lost weight, compared with a slight increase in the comparator group.
SUSTAIN (Japan, sitagliptin): published
|Patient population: Japanese patients with type 2 diabetes treated with lifestyle management or monotherapy||Comparator treatment: sitagliptin|
In this trial, published in Diabetes, Obesity and Metabolism, Japanese patients received weekly semaglutide 0.5 or 1.0 mg or daily oral sitagliptin 100 mg (after washout of pre-existing treatments). Glycated hemoglobin fell by 1.9–2.2% with semaglutide versus 0.7% with sitagliptin, which was a significant difference. There were more adverse effects among patients treated with semaglutide than sitagliptin, most commonly constipation, nausea, and diarrhea.