A 40-week randomized trial found that adding once-weekly semaglutide 2.0 mg to a reduced dose of insulin glargine lowered HbA1c and body weight more than continuing to titrate insulin glargine alone in adults with type 2 diabetes and overweight.
The study also reported lower daily insulin requirements and fewer severe hypoglycemia events in the semaglutide group. Gastrointestinal side effects were more common. These findings come from one specific trial population and do not mean that everyone using insulin should add semaglutide or reduce insulin.
Key takeaways
- The trial included 573 adults with type 2 diabetes, overweight, and treatment with basal insulin.
- After 40 weeks, semaglutide plus reduced insulin glargine lowered HbA1c more than titrated insulin glargine alone.
- Average body weight was also lower with the semaglutide strategy.
- Severe hypoglycemia was less frequent, but gastrointestinal events were more common.
- The study was open-label and funded by Novo Nordisk, so the findings need to be interpreted with appropriate caution.
What did SUSTAIN OPTIMIZE study?
SUSTAIN OPTIMIZE was a phase 3b, open-label, randomized study. Adults with type 2 diabetes, a body mass index of at least 25, and basal insulin use of up to 40 units per day were assigned to one of two treatment strategies.
One group received once-weekly semaglutide 2.0 mg alongside a dose-reduced insulin glargine regimen. The comparison group continued insulin glargine with dose titration. The trial lasted 40 weeks and assessed HbA1c, body weight, daily insulin dose, treatment satisfaction, and safety.
What did the trial find?
Semaglutide plus reduced insulin glargine performed better than titrated insulin glargine alone on the main glucose outcome. The estimated difference in HbA1c change between the groups was 0.74 percentage points in favor of the semaglutide strategy.
Body weight also fell more in the semaglutide group. The estimated between-group difference was 8.5 kg. The semaglutide group also used less daily insulin by the end of the study and reported better treatment-satisfaction scores.
Severe hypoglycemia was less frequent with the semaglutide strategy. The reported rate ratio was 0.45, although individual risk can vary with insulin dose, food intake, kidney function, activity, illness, and other medicines.
What about side effects?
No new safety concerns were identified during the trial, but gastrointestinal events were much more common with semaglutide plus reduced insulin glargine. The study reported 310 gastrointestinal events in the semaglutide group compared with 32 in the titrated-insulin group.
Gastrointestinal symptoms can include nausea, vomiting, diarrhea, constipation, abdominal discomfort, or reduced appetite. Persistent vomiting or diarrhea can contribute to dehydration and may affect glucose levels and medication safety. Anyone with severe or ongoing symptoms should contact their healthcare team.
What are the limitations?
The trial was randomized, which helps make the groups comparable, but it was open-label. Participants and clinicians knew which treatment strategy was being used. The study also lasted 40 weeks, so it cannot answer every question about long-term weight maintenance, cardiovascular outcomes, kidney outcomes, or rare adverse effects.
The results apply most directly to adults with type 2 diabetes and overweight who were using basal insulin within the trial’s eligibility range. They should not automatically be applied to people with type 1 diabetes, people using multiple daily injections or insulin pumps, people with very different kidney function, or people using other treatment combinations.
The study was funded by Novo Nordisk. Funding does not by itself determine whether results are reliable, but it is important context when interpreting a medication trial.
What should people using insulin do?
Do not reduce, stop, or add insulin or semaglutide based on this article. Insulin changes can cause dangerous high or low glucose if they are not planned and monitored.
If your HbA1c remains above your agreed target, or if insulin-related weight gain or low glucose is a concern, ask your diabetes team whether an approved treatment strategy could be appropriate. The decision may depend on your glucose pattern, kidney function, heart health, weight goals, history of hypoglycemia, side effects, cost, and access.
If semaglutide is prescribed, ask how to monitor glucose while insulin is adjusted, what symptoms require urgent help, and how to manage reduced appetite, vomiting, diarrhea, or missed meals.
The bottom line
In SUSTAIN OPTIMIZE, semaglutide 2.0 mg added to a reduced insulin glargine regimen improved HbA1c and weight more than titrated insulin glargine alone over 40 weeks in adults with type 2 diabetes and overweight. It also reduced severe hypoglycemia in the study, while gastrointestinal events were more common.
This is useful evidence for a clinician-guided treatment discussion, not a universal treatment rule. The trial’s population, open-label design, limited follow-up, and industry funding all belong in the conversation.
Source
Rodbard HW et al. Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE). Diabetes, Obesity and Metabolism. 2026. PubMed record. DOI: 10.1111/dom.71132.
Medical note: This article is for general education and does not replace individualized medical advice. Do not change insulin or other medicines without guidance from your diabetes care team.