Off-label semaglutide, tirzepatide lower HbA1c and body weight in type 1 diabetes
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Key takeaways:
- Adults with type 1 diabetes had significant declines in body weight at 1 year of off-label semaglutide and tirzepatide use.
- Use of both medications was associated with reductions in total daily insulin dose.
Adults with type 1 diabetes using either semaglutide or tirzepatide off-label had greater decreases in body weight and HbA1c than those not treated with either medication, according to a speaker.
As Healio previously reported, researchers at the Barbara Davis Center for Diabetes at University of Colorado Anschutz Medical Campus found adults with type 1 diabetes and overweight or obesity using tirzepatide (Mounjaro/Zepbound, Eli Lilly) off-label had a 0.67 percentage point reduction in HbA1c and an 18.5% decrease in body weight at 1 year. At the European Association for the Study of Diabetes annual meeting, University of Colorado researchers presented more data from their institution of adults with type 1 diabetes who used tirzepatide as well as semaglutide (Ozempic/Wegovy, Novo Nordisk) off-label.
“Off-label semaglutide and tirzepatide treatment resulted in significant weight loss and improved glycemic control in adults with type 1 diabetes, with no reported hospitalization for hypoglycemia or diabetic ketoacidosis,” Janet Snell-Bergeon, PhD, professor of pediatrics at the Barbara Davis Center for Diabetes at the University of Colorado Anschutz Medical Campus, said during the presentation.
Researchers conducted a retrospective chart review of 50 adults with type 1 diabetes and overweight or obesity who used semaglutide off-label and 50 adults who used tirzepatide off-label. Propensity score matching was used to compare data from semaglutide and tirzepatide users with 50 controls with type 1 diabetes and overweight or obesity who were not treated with either medication. Changes in BMI, body weight and HbA1c were assessed over a 1-year period.
Reductions in weight, HbA1c
Adults using tirzepatide had a 7.5 kg/m2 decline in BMI and semaglutide users a 3 kg/m2 decrease in BMI from baseline to 12 months (P for treatment difference < .0001). The tirzepatide group had a significantly greater reduction in BMI than controls starting at 3 months and continuing until the end of the study, whereas semaglutide users had a significantly greater decrease in BMI than controls beginning at 6 months and continuing through 1 year.
The tirzepatide group lost 21.4% of their body weight from baseline to 1 year and the semaglutide group achieved a 9.1% weight reduction in that same period (P for treatment difference < .0001). A weight loss of 10% or more at 1 year was achieved by 87% of adults using tirzepatide and 47% of those using semaglutide compared with no participants in the control group (P < .001).
Adults using semaglutide had a 0.54 percentage point decline in HbA1c at 1 year compared with a 0.68 percentage point decrease for those using tirzepatide. Both decreases were greater than the change in the placebo group (P = .008).
Change in total, basal and bolus insulin daily dose was significantly lower for adults using tirzepatide than those using semaglutide or controls. At 1 year, there was no significant difference in the change in total, basal or bolus insulin dose between the semaglutide and control groups.
“When we looked at total insulin dose per kilogram of body weight, there was a significant decrease [with tirzepatide], indicating that this went beyond just the loss of body weight and perhaps improved insulin sensitivity,” Snell-Bergeon said.
The change in BMI, body weight and HbA1c did not differ between adults receiving multiple daily insulin injections and those using an insulin pump. Snell-Bergeon said there was a trend toward greater HbA1c loss for adults receiving tirzepatide and using an insulin pump vs. semaglutide users or those using tirzepatide with multiple daily injections.
Dosing and safety
People using semaglutide began at a starting dose of 0.25 mg per week and were titrated up based on clinical guidelines. Of the group, 38 reached a maximum dose of 0.5 mg per week. For those using tirzepatide, the starting dose was 2.5 mg per week. Of the tirzepatide group, 16 reached a maximum dose of 5 mg, eight reached a maximum dose of 7.5 mg and 14 reached a maximum dose of 10 mg.
There were no reports of hospitalizations for DKA or hypoglycemia during the study. Three adults using semaglutide and one using tirzepatide discontinued the medication due to lack of response.
Snell-Bergeon said randomized controlled trials still need to be conducted to assess efficacy and safety outcomes for both medications among adults with type 1 diabetes.
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Snell-Bergeon J, et al. OP 43. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid.
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