Loading ...

CHICAGO — Once-weekly semaglutide improved glycemia and reduced weight without increasing hypoglycemia in adults with type 1 diabetes (T1D) and obesity, new research presented at the American Diabetes Association (ADA) 85th Scientific Sessions found.

The study results were simultaneously published in NEJM Evidence.

“Semaglutide was effective in lowering or improving time in range, without increasing time below range; it produced weight loss of at least 5%; and it was very safe,” said lead investigator Viral N. Shah, MD, professor of medicine and director of diabetes clinical research at the Center for Diabetes and Metabolic Diseases, Indiana University, Indianapolis.

“We didn’t find any difference in severe hypoglycemia between semaglutide and a placebo, and we did not find any [diabetic ketoacidosis] in the entire study,” Shah told Medscape Medical News.

“I think the results are very encouraging, and I hope that industry will take it on and do a regulatory approval trial for semaglutide in type 1,” he added.

Over a Third Met Composite Endpoint

The 26-week ADJUST-T1D randomized clinical trial investigated semaglutide vs placebo in 72 adults with T1D and obesity (BMI ≥ 30) who were using automated insulin delivery (AID) systems. The trial was investigator-initiated and funded by Breakthrough T1D, not Ozempic manufacturer Novo Nordisk, although the company did provide the drug.

A total of 72 patients were randomized 1:1 to receive once-weekly semaglutide, up to 1 mg, or placebo for 26 weeks. Participants had a mean age of 40 years, a mean diabetes duration of 23 years, a mean baseline A1c of 7.8, BMI 35, and body weight 102 kg. Two thirds were using the Tandem Control IQ AID system.

The primary endpoint was a composite of continuous glucose monitoring (CGM)-based time in range 70-180 mg/dL of > 70%; time below 70 mg/dL of < 4%; and ≥ 5% weight reduction.

A total of 13 of the 36 (36.1%) in the semaglutide group vs zero in the placebo group met the composite endpoint. The between-group difference was 36 percentage points (P < .001). Semaglutide treatment was associated with a nearly eightfold better chance of achieving the primary outcome (odds ratio, 7.77).

Among the secondary outcomes, A1c reductions from baseline to week 26 were 0.7 with semaglutide vs 0.4 with placebo; increased percent time in range was 11.1% vs 2.3%; reductions in CGM mean glucose were 15.7 mg/dL vs 3.6 mg/dL; and reductions in percentage time above 180 mg/dL were 11.1% vs 2.7%. All of those differences were significant, Shah reported.

The percentage of time spent below 70 mg/dL from baseline was low and the change from baseline didn’t differ significantly between the two groups, 0.1% vs 0.4%.

Body weight change at 26 weeks were reductions of 9.2 kg vs 0.4 kg, and BMI drops were 3.3 vs 0.2. Those differences were also significant, Shah said.

Daily insulin requirements from baseline to week 26 were reduced significantly by 22.3 units per day with the semaglutide group compared to the placebo group.

A total of 57 gastrointestinal events were reported by 19 patients in the semaglutide group vs 13 gastrointestinal events were reported by 9 patients in the placebo group. Two from each group experienced severe hypoglycemia. There were no diabetic ketoacidosis events in either group.

The number of people who discontinued the trial early due to persistent gastrointestinal adverse events was three in the placebo group vs two in the semaglutide group.

‘Prohibitively Expensive for Those With T1D’

Asked to comment, Nicholas B. Argento, MD, senior clinical endocrinologist and diabetes technology director at the Maryland Endocrine and Diabetes Center, Columbia, Maryland, said that the trial “was small but showed the benefit of using adjunctive therapy in T1D.” 

There is an “unmet need” in patients with T1D with a high BMI and suboptimal glycemic control, he told Medscape Medical News

Despite proven cardiorenal benefits of both GLP-1 agonists and SGLT2 inhibitors in type 2 diabetes, “none are approved for use in T1D, which means that they are generally not covered by insurance.” These medications “end up being prohibitively expensive for those withT1D to access,” Argento noted.

But there is no reason to believe we would not see similar benefits in those with T1D, who have a very high cardiorenal risk, he said. “ADJUST-T1D shows that T2D agents like semaglutide can definitely benefit T1Ds with no safety concerns.” 

For the time being, Shah pointed to this section of the ADA Standards of Care that was just added in the 2025 edition: 

A diagnosis of type 1 diabetes does not preclude also having features classically associated with type 2 diabetes (eg, insulin resistance, obesity, and other metabolic abnormalities), and until more precise subsets are used in clinical practice, it may be appropriate to categorize such an individual as having features of both type 1 and type 2 diabetes to facilitate access to appropriate treatment (eg, glucagon-like peptide 1 receptor agonist [GLP-1 RA] or sodium–glucose cotransporter 2 [SGLT2] inhibitor therapies for potential weight and other cardiometabolic benefits) and monitoring systems.

“We use that language from the Standards of Care in prior authorization,” Shah told Medscape Medical News.

Independent Industry Consultant Charles Alexander, MD, told Medscape Medical News, “This small study is very encouraging but unlikely to lead to [US Food and Drug Administration] approval for semaglutide in T1D. In contrast, two much larger currently recruiting global studies of tirzepatide in T1D NCT06914895 and NCT06962280 are more likely to lead, if successful, to FDA approval.”

Shah received research support from, does consulting, speaking, and/or serves on advisory boards for Alexion, Novo Nordisk, Dexcom, Enable Bioscience, Zucara Therapeutics, Lilly, Breakthrough T1D, NIH, Insulet, Tandem Diabetes Care, Medtronic, Ascensia Diabetes Care, Embecta, Sanofi, Sequel Med Tech, Biomea Fusion, Lumosfit, and Genomelink. Argento has consulted or been on advisory boards for Eli Lilly Diabetes, Dexcom, DiabeLoop, ConvaTec, and Senseonics and served on the speakers’ bureaus for Boehringer-Ingelheim, Dexcom, Eli Lilly Diabetes, MannKind, Novo Nordisk, Xeris, and Zealand Pharmaceuticals. Alexander had no disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social.