GLP-1s Eyed as Key to Managing T1D With Obesity

The adjunctive use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) as an addition to insulin is increasingly viewed as a method for addressing the rising prevalence of obesity in type 1 diabetes (T1D).

Current GLP-1 RA drugs, such as semaglutide and the dual glucagon-insulinotropic peptide (GIP)/GLP-1 tirzepatide, are approved for treating type 2 diabetes (T2D) (Ozempic and Mounjaro, respectively) and obesity (Wegovy and Zepbound, respectively) but not for T1D. While insulin remains essential for treating T1D, new thinking is that weight loss with GLP-1 RAs would also enable insulin dose reduction and add cardiorenal benefit in those with overweight or obesity.

“When many of us went to medical school decades ago, we were told that people with type 1 diabetes were lean and thin. That was one of the ways to demarcate between type 1 and type 2 diabetes. Obviously, that is not the case anymore,” Satish K. Garg, MD, professor of medicine and pediatrics at the Barbara Davis Center for Diabetes, University of Colorado Denver, said at the Advanced Technologies & Treatments for Diabetes (ATTD) 2025 meeting.

Data from several sources, including one study from the T1D Exchange by Garg and colleagues, showed that approximately two thirds of people in the United States with T1D have overweight or obesity and that it confers additional health risk. “Clearly, there are risk factors when you add another fuel to the fire,” said Garg, who is editor-in-chief of Diabetes Technology & Therapeutics.

Type 1 With Obesity or Type 1 plus Type 2?

A related topic in the field right now is whether people with T1D who also have obesity with extreme insulin resistance should also be diagnosed with T2D, Rozalina G. McCoy, MD, associate division chief for Clinical Research, Division of Endocrinology, Diabetes, and Nutrition at the University of Maryland School of Medicine, Baltimore, told Medscape Medical News.

“A person can absolutely have both, and we need to treat them for both. I think that’s the big gap in care for many. Type 2 is just insulin resistance that has become so severe it causes hyperglycemia. You can have both insulin resistance and deficiency,” McCoy said.

The terminology is important because of the treatment implications. “Is the best treatment higher and higher doses of insulin, or is it a GLP-1 or [sodium-glucose cotransporter 2 (SGLT2) inhibitor] together with lower doses of insulin? You wouldn’t treat type 2 with high doses of insulin right away. A long time ago if you had type 2 and type 1 together your only option was insulin…but now we have type 2 medications that are pancreas agnostic, and we can use those so that patients don’t have to take very high doses of insulin, which is safer and better in the long term. We need the research, but I think we need to start shifting the paradigm away from mutually exclusive, because they’re not,” she said.

McCoy acknowledged that diagnostic coding for both might present a challenge, however, she noted, she has successfully navigated this process so that the patient’s insurance covered a GLP-1 RA medication.

Garg told the international ATTD audience that he uses the “double diabetes” diagnosis often in the United States to get drugs approved for people with T1D. “Since the drugs are not approved for type 1 diabetes you have to put a diagnosis of type 2 diabetes in the [electronic medical record].”

Obesity Prevalent in T1D with Possible Causal Role

Shlomit Shalitin, MD, professor of pediatrics at Tel Aviv University, Tel Aviv, Israel, presented an overview of obesity in both adults and children with T1D, a trend that mirrors the worldwide obesity epidemic. Upward trends in overweight and obesity in adults with T1D seen in other countries, including Finland, Sweden, Italy, and Germany/Austria, mirror those of the United States.

In four pediatric T1D registries, prevalence of overweight/obesity ranged from 15.3% in Germany/Austria during 1995-2011 to 36.0% in the United States during 2016-2018. A 2022 meta-analysis showed that children with T1D had higher total body fat mass than children without diabetes.

Several factors contribute to weight gain in T1D, including use of exogenous insulin, fear of hypoglycemia leading to caloric intake and lack of exercise, psychological factors, and disruption of food regulation, said Shatilin, who is also with the National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel.

Obesity in T1D can exacerbate insulin resistance leading to inadequate glycemic control, as well as increase the risk for both cardiovascular and microvascular complications even after adjustment for age, diabetes duration, and A1c.

Moreover, Shalitin noted there is evidence obesity plays a role in T1D development, via the “accelerator hypothesis,” that obesity-induced insulin resistance places increased burden on pancreatic islets in people who are already genetically at risk, increasing insulin demands and inducing or accelerating autoimmune destruction.

“The presence of obesity in patients with T1D has an impact on their glycemic control and long-term health. Therefore, prevention and treatment of overweight/obesity remains a high priority for people with T1D,” she concluded.

GLP-1 RAs in Type 1: The Data Point to Benefit 

Garg summarized data demonstrating significant weight loss and improved A1c in T1D with the newer generation medications. Other T2D medications, including metformin, Dipeptidyl Peptidase-4 (DPP-4 inhibitors), pramlintide, older generation GLP-1 RAs, and SGLT2 inhibitors, have also been studied in T1D but none have produced the same weight loss and A1c benefits, he noted.

In one study, 10 patients with new-onset T1D were started on a regimen that included insulin and semaglutide. At 3 months, none were on prandial insulin and at 10 months, seven were off insulin. However, it’s likely that at least some of these individuals were in the so-called “honeymoon phase” with residual insulin secretion, he noted.

In Garg’s own pilot study, a retrospective chart review of 50 patients with T1D and overweight or obesity, those who received off-label semaglutide had significantly greater declines in body mass index, weight, and continuous glucose monitor time-in-range than control individuals with T1D.

His group has also published a similarly small study with tirzepatide in 62 patients, showing an average 18% weight loss, along with significant A1c improvement. And in another of their studies including 150 patients with T1D, weight loss was twice as great with tirzepatide (21.4%) than with semaglutide (9.1%).

In a recent double-blind, randomized, crossover trial of semaglutide with automated insulin delivery in 28 patients with T1D, semaglutide increased time in range significantly (P = .006) compared with placebo, without increasing hypoglycemia.

And in another of Garg’s studies, 84 adults with T1D and overweight or obesity who had used tirzepatide for at least 6 months were matched on clinical factors including body mass index, age, diabetes duration, and A1c with 38 nontirzepatide users.

Over 21 months, those using tirzepatide lost an average of 59 pounds while the control individuals gained 1.7 pounds. After adjustments for weight and A1c, those on tirzepatide also had greater decreases over baseline in A1c (P = .017) and greater improvements in low-density lipoprotein cholesterol, triglycerides, blood pressure, and estimated glomerular filtration rate (eGFR). The eGFR declined significantly in control individuals but not in the tirzepatide users.

Garg concluded by citing a 2024 study, showing off-label prescribing of both GLP-1 RAs and SGLT2 inhibitors in T1D increased significantly between 2010 and 2023, often associated with elevated cardiorenal risk profiles.

“Whether it’s type 2 diabetes or type 1 diabetes, both have high risk of cardiovascular death and diabetic kidney disease. If these drugs are known to prevent both of those events, it makes sense to use those drugs irrespective of the diagnosis of type 1 and type 2,” he concluded.

Garg is on advisory boards for, consults for, and/or receives research grants from Medtronic, Novo Nordisk, Bayer, Dexcom, Roche Diagnostics, Abbott Diabetes Care, Know Labs, Eli Lilly, and Diasome. All research grants and honoraria are received through the University of Colorado Denver. He does not own stocks in any device or pharmaceutical company. McCoy served as a consultant to EmmiEducate (Wolters Kluwer). She is an investigator at the University of Maryland Institute for Health Computing, which is supported by funding from Montgomery County, Maryland, and the University of Maryland Strategic Partnership: MPowering the State, a formal collaboration between the University of Maryland, College Park, and the University of Maryland, Baltimore. Shalitin 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.