NEW ORLEANS — Incretin-based therapies have not yet been approved for type 1 diabetes (T1D), but they are increasingly being used off-label. Clinicians and patients are eagerly awaiting news from randomized clinical trials to verify safety and efficacy so these treatments can be approved.

It therefore seemed like good news when results of a phase 2 clinical trial showed that a novel investigational GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (RA), acmopatide (CT-868), reduced weight, insulin use, and A1c levels in patients with T1D.

In the trial, 111 adults with T1D who had a BMI ≥ 27 were randomly assigned to receive the drug in doses of 1.8 mg, 4.1 mg, or 6.6 mg or placebo for 16 weeks.

The 4.1-mg dose reduced A1c by 0.34 percentage points from a baseline 7.5%, and 56% achieved an A1c < 7.0%. Weight was reduced by up to 7% and insulin doses were reduced by up to 15% compared with placebo. There were no major safety concerns.

Despite these findings, which were presented at the American Diabetes Association (ADA) 2026 Scientific Sessions, the manufacturer, Roche (which had acquired the drug’s developer Carmot Therapeutics), decided not to move forward with the drug, citing business reasons. One of the speakers announced the decision at the end of the hour-long session.

The news came as a disappointment to those at the meeting.

Nicholas B. Argento, MD, an endocrinologist in Columbia, Maryland, whose practice focuses on T1D, expressed dismay at the manufacturer’s decision not to bring acmopatide forward.

“It’s shameful that something with these kinds of results is not being brought to market,” he said.

Argento, who often prescribes GLP-1s to his patients with T1D, said that “the difficulty with off-label is getting coverage.”

Insurance coverage is “hit or miss,” and when it doesn’t work, patients who can afford it will often self-pay “but that’s beyond the reach of most people.”

Session speaker Klara Klein, MD, PhD, assistant professor in the Division of Endocrinology and Metabolism at the University of North Carolina at Chapel Hill (UNC-Chapel Hill), told Medscape Medical News that despite Roche’s decision not to go ahead, she thinks “these data are very important.”

“There is every reason to be extremely excited about the possibility of these therapies for people with [T1D],” she said.

Of course, “from a clinician standpoint, we need these drugs to be evaluated for safety and efficacy,” added Klein, who is director of the Endocrinology, Diabetes, and Obesity Clinical Research Unit at UNC-Chapel Hill. “We need to have them approved because there are obviously clear benefits.”

New Guidance for Adjunctive Use of Incretin Therapies

In order to help clinicians who are prescribing these medications in T1D, new guidelines — “Adjunctive Treatment with GLP-1 and Dual GLP-1/GIP Receptor Agonists for People with Type 1 Diabetes: Consensus Report and Practical Guidelines for Safe Use” — were published recently in Diabetes Technology & Therapeutics.

The effort was initiated and funded by the diaTribe Foundation, with endorsement from the Advanced Technologies & Treatments for Diabetes, IDF Europe, American Association of Clinical Endocrinology, Breakthrough T1D, International Society for Pediatric and Adolescent Diabetes, and the Association of Diabetes Care & Education Specialists.

“Without regulatory approval for the T1D indication, access and opportunities for people with T1D to engage with important education regarding the safety of GLP-1 and GLP-1/GIP RA therapy may be limited,” first author Satish K. Garg, MD, founder and director of the Adult Clinic of the Barbara Davis Center for Diabetes at the University of Colorado in Aurora, and colleagues wrote.

There is concern about lack of support for optimized diabetes management along with expected insulin dose changes, with potential safety risks including hypoglycemia or hyperglycemia-related ketosis, the authors noted.

Both obesity and cardiovascular disease are common in people with T1D, said Garg, noting that weekly semaglutide and tirzepatide are available for people with T1D via the obesity indication.

The new guidance addresses the use of both adjunctive GLP-1 and dual GLP-1/GIP RAs in people with T1D.

The recommendations include:

• Consider GLP-1 and GLP-1/GIP RA therapy with newer agents (eg, semaglutide or tirzepatide) for adults (or semaglutide for adolescents) living with T1D and overweight/obesity or normal BMI who are not achieving glycemic targets with insulin alone and who may benefit from cardiovascular or renal outcomes.
• When prescribing a GLP-1 or GLP-1/GIP RA to someone with T1D, start at a lower dose and escalate slowly as tolerated. For some, dose escalation every 2-3 months rather than monthly may be necessary.
• Provide all individuals initiating a GLP-1 or GLP-1/GIP RA with detailed instructions on insulin adjustment (a table is provided), ketone monitoring, and sick day protocols.
• Consider reducing the GLP-1 or GLP-1/GIP RA dose once weight loss and glycemic goals are met, along with insulin dose readjustment.
• At a minimum, all people with T1D starting on a GLP-1 or GLP-1/RA should be using continuous glucose monitoring (CGM), and use of an automated insulin delivery system is preferable. Insulin dose adjustment instructions using CGM metrics should be provided.
• Remote or in-person follow-up at 4- to 8-week intervals is recommended, with insulin regimens reassessed at each clinical encounter.
• Insulin should never be stopped in people with T1D on GLP-1 or GLP-1/GIP RAs, even when A1c goals are attained.
• Monitoring and treating gastrointestinal (GI) adverse events are necessary because GI side effects are common in people with T1D.
• Exercise caution in people with T1D who have gastroparesis or are at risk for it due to long-duration T1D or autonomic dysfunction because GLP-1 and GLP-1/GIP RAs can exacerbate gastric dysmotility.
• Retinal exams should be considered within 12 months prior to initiating a GLP-1 or GLP-1/GIP RA or closer to initiation if there are concerns about retinopathy.
• Women with T1D must be advised to stop GLP-1 and GLP-1/GIP RA therapy when pregnant or trying to conceive.
• Individualized approaches are recommended for planned surgery.

The document also advises payers to limit out-of-pocket costs and support access to GLP-1 and GLP-1/GIP RA therapy for those who are most likely to benefit due to obesity/insulin resistance and/or elevated cardiovascular risk.

Evidence Thus Far Supports Benefit in T1D

The paper also summarizes the evidence to date, mostly from observational trials, finding significant long-term (> 12 months) weight loss, A1c reduction, and benefits in surrogate cardiovascular disease markers with GLP-1 and GLP-1/GIP RA use in adults and adolescents with T1D.

One small randomized trial showed such benefits with semaglutide, and Eli Lilly is currently conducting a larger phase 3 randomized trial of tirzepatide in people with T1D.

Garg has received consulting fees and honoraria for participation on advisory boards for Medtronic, Roche Diagnostics, Abbott Diabetes Care, Dexcom, Novo Nordisk, Vertex, and Eli Lilly and research grants from Eli Lilly, Novo Nordisk, Medtronic, and Dexcom. He has also received support for attending meetings or travel from Abbott Diabetes Care, Dexcom, Eli Lilly, and Novo Nordisk. Klein has consulted for Antag Therapeutics, Metsera, Novo Nordisk, Roche Pharmaceuticals, and vTv Therapeutics. She has received research-related contracts paid to her institution from Bayer, Boehringer Ingelheim, Carmot, Diasome, Eli Lilly, GentiBio, Novo Nordisk, Rhythm Pharmaceuticals, Roche Pharmaceuticals, and vTv Therapeutics. Argento reported being a speaker for Eli Lilly, Novo Nordisk, and Boehringer Ingelheim.

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 @MiriamETucker and BlueSky @miriametucker.bsky.social.