Trial finds weekly semaglutide 1.0 mg reduced A1C and weight more than daily liraglutide

A head-to-head trial of 577 adults with type 2 diabetes found that once-weekly semaglutide 1.0 mg lowered blood sugar and body weight more than once-daily liraglutide 1.2 mg over 30 weeks, while causing more gastrointestinal side effects and more treatment discontinuations ^[1].

The study, called SUSTAIN 10, was a phase 3b, open-label trial. It randomized 577 adults with type 2 diabetes in a 1:1 ratio to either subcutaneous semaglutide 1.0 mg once a week or subcutaneous liraglutide 1.2 mg once a day. Participants started with A1C levels between 7.0% and 11.0% and were already taking one to three oral diabetes drugs. Both drugs belong to the GLP-1 receptor agonist class. The main goal was change in A1C at week 30, and change in body weight was a confirmatory secondary goal ^[1].

A1C fell by an average of 1.7 percentage points with semaglutide and 1.0 point with liraglutide, from a baseline average of 8.2%. The estimated difference between the groups was 0.69 points in favor of semaglutide (95% confidence interval, 0.56 to 0.82; P<0.0001) ^[1].

Weight fell by an average of 5.8 kg with semaglutide and 1.9 kg with liraglutide, from a baseline average of 96.9 kg. The estimated difference was 3.83 kg in favor of semaglutide (95% CI, 3.09 to 4.57; P<0.0001) ^[1].

More people taking semaglutide reached A1C targets below 7.0% and at or below 6.5%, lost at least 5% and at least 10% of their body weight, and met a combined goal of A1C below 7.0% with no severe or blood-sugar-confirmed symptomatic hypoglycemia and no weight gain. All of those differences were statistically significant (P<0.0001), but the published results do not give the percentage of people who reached each target ^[1].

The two drugs had similar safety profiles overall with one exception: gastrointestinal disorders, the most common side effects, were more frequent with semaglutide, 43.9% versus 38.3%. Side effects that led people to stop treatment early also were more common with semaglutide, 11.4% versus 6.6%. The trial's conclusion was that semaglutide was superior for lowering A1C and body weight and that safety was generally similar except for the higher rate of gastrointestinal side effects ^[1].

Why it matters for patients

This trial compares two injected GLP-1 receptor agonists that are already used to treat type 2 diabetes, not a new drug against a placebo, so the results speak to a choice some patients and prescribers already weigh: a weekly injection versus a daily one ^[1].

The pattern is a tradeoff rather than a clear win on every measure. On average, the semaglutide group got larger reductions in A1C and weight, and more people in that group hit blood sugar and weight-loss targets. At the same time, more people in the semaglutide group reported gastrointestinal problems and more stopped treatment before week 30 ^[1].

Averages from a trial do not predict what one person will experience, and the report does not say how severe the gastrointestinal side effects were or why people stopped. Because the trial was open-label, participants and their doctors knew which drug was being used, which can influence how side effects are reported ^[1].

The trial enrolled only adults with type 2 diabetes who were taking one to three oral diabetes drugs, with A1C between 7.0% and 11.0%. Results may not carry over to people using these medicines for weight loss without diabetes, to people with different starting A1C levels, or to higher semaglutide doses. The report includes no comparison with tirzepatide, no information on cost, insurance coverage or availability in the United States, and no results for heart, kidney or other longer-term outcomes ^[1].

What happens next

No follow-up beyond week 30 is described in the published results, and whether the differences between the two drugs persist over a longer period has not been reported. A commentary titled "Efficacy of semaglutide versus liraglutide in clinical practice" was published in the journal Diabetes & Metabolism in November 2020, with no abstract available ^[1].