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The phase III SYNCHRONIZE-2 trial found that survodutide led to greater average weight loss and HbA1c reductions than placebo over 76 weeks in adults with type 2 diabetes and obesity. Gastrointestinal adverse events were common, and 18% of participants in each dose group stopped the trial regimen because of them; the drug remains investigational.
The investigational dual GIP/GLP-1 agonist survodutide produced greater weight loss and HbA1c reductions than placebo over 76 weeks in adults with type 2 diabetes and obesity, but gastrointestinal side effects led 18% of participants in each dose group to discontinue the trial regimen. The phase III SYNCHRONIZE-2 results were presented at the European Association for the Study of Diabetes meeting in Milan and published in the New England Journal of Medicine.
Participants received once-weekly injections of 3.6 mg survodutide, 6 mg survodutide, or placebo. By week 76, average body weight had fallen 8.2% in the 3.6-mg group and 9.8% in the 6-mg group, compared with 3.9% with placebo. At least 5% weight loss was recorded for 57.6%, 64.5%, and 35.1% of participants, respectively; the reported comparisons with placebo had P values below 0.001.
Mean HbA1c, a measure of blood sugar over time, declined from a baseline average of 7.4% by 0.9 percentage points with 3.6 mg and 0.8 points with 6 mg, versus 0.2 points with placebo. Sean Wharton, MD, of Wharton Medical Clinic Weight and Diabetes Management in Hamilton, Ontario, presented the results. He said survodutide was also associated with changes in systolic blood pressure, waist circumference and lipid measures.
Gastrointestinal adverse events occurred in 73% to 78% of participants receiving survodutide, compared with 38.6% on placebo. The trial report described most events as mild to moderate and transient. Nonetheless, 18% in each survodutide group stopped the trial regimen because of gastrointestinal events, against 1.2% in the placebo group. Discontinuations for any adverse event were 26% in each active-treatment group and 9% with placebo.
Weight Benefits Come With Tolerability Costs
The findings show a measurable benefit over placebo for both body weight and blood sugar in the population studied. But stopping treatment can limit how many patients are able to continue long enough to receive its effects. The difference in gastrointestinal-related discontinuations is therefore a central part of the results, not a secondary detail.
At the meeting, Andreas Birkenfeld, MD, PhD, of University Hospital Tübingen, said there was no additional safety signal beyond what was already known, while warning that gastrointestinal discontinuation rates were markedly higher than those reported for some other agents. He cited rates of up to 5% with high-dose semaglutide and up to 2% with investigational retatrutide. Those figures are comparisons cited at the meeting, not results from a head-to-head trial, so they do not establish which treatment is safer or more effective for an individual patient.
The study authors said the 9.8% weight loss in the higher-dose group was a magnitude associated with cardiovascular benefits and fewer metabolic and mechanical complications, as well as better quality of life. That statement describes expected associations; SYNCHRONIZE-2 did not establish that survodutide prevents cardiovascular events.
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How SYNCHRONIZE-2 Was Conducted
The multinational, double-blind trial enrolled 752 adults: 250 assigned to 3.6 mg, 251 to 6 mg and 251 to placebo. Participants had type 2 diabetes and a body mass index of at least 27. Their mean age was 55.7 years, mean BMI was 36.5, and 49.3% were men. Treatment was given by weekly subcutaneous injection.
The authors reported that weight loss was lower than the maximum 13% reported in SYNCHRONIZE-1, an earlier trial that excluded participants with diabetes. Results across separate trials should be interpreted cautiously because their populations and study conditions differ. The source report also noted that survodutide’s weight and HbA1c results were below figures reported for some other medicines, but those cross-trial figures do not provide a direct comparison.
SYNCHRONIZE-2 excluded people taking insulin. Most participants had relatively well-controlled blood sugar at baseline while using oral glucose-lowering medicines. The findings may not apply in the same way to people with more difficult-to-control diabetes or those using insulin.
“Survodutide was associated with improvements in other cardiometabolic parameters, including systolic blood pressure, waist circumference, and lipids.”
— Sean Wharton, MD, presenting the trial findings
Questions About Use and Tolerability
The results do not establish how survodutide compares with other medicines in a direct, randomized head-to-head trial. Nor do they show whether the reported weight and HbA1c changes translate into fewer heart attacks, strokes or other long-term complications. A cardiovascular outcomes trial is ongoing, with data expected later this year, according to the source report.
It is also not clear from the reported findings whether changing the dose-escalation schedule will reduce side effects or discontinuations without affecting treatment outcomes. The trial excluded people taking insulin, limiting conclusions for that group. Survodutide remains investigational; these findings alone do not establish its approval status or suitability for any individual patient.
Flexible Dosing and Outcomes Data Ahead
Developer Boehringer Ingelheim said upcoming trials will use more flexible, patient-centered titration strategies intended to improve tolerability. The results will be needed to determine whether a different approach to increasing doses can address gastrointestinal-related discontinuations.
Data from a separate cardiovascular outcomes trial are expected later this year, according to the report. Until those findings and further trial results are available, the balance between survodutide’s observed weight and blood-sugar effects and its tolerability remains under study.
Key Questions
How much weight did participants lose with survodutide?
At week 76, average weight loss was 8.2% with 3.6 mg and 9.8% with 6 mg, compared with 3.9% with placebo.
How often did participants stop treatment because of gastrointestinal events?
18% of participants in each survodutide dose group discontinued the trial regimen because of gastrointestinal events, compared with 1.2% in the placebo group.
Did survodutide lower blood sugar in the trial?
Yes. Mean HbA1c fell by 0.9 percentage points with 3.6 mg and 0.8 points with 6 mg, compared with a 0.2-point decline with placebo.
Can these results be applied to people with diabetes who use insulin?
The trial excluded people taking insulin, so its results may not apply directly to that group. Most participants had relatively well-controlled blood sugar while taking oral glucose-lowering medicines.
Is survodutide approved for treating obesity or diabetes?
The source describes survodutide as an investigational medicine. The trial findings do not establish that it is approved or appropriate for a particular patient.
Source: rss
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