Tirzepatide Significantly Reduces HbA1c, Body Weight in Type 1 Diabetes

Viral N. Shah, MD

Credit: University of Colorado School of Medicine

Results from a recent proof-of-concept observational study provided insight into the potential efficacy and safety of tirzepatide among adults with type 1 diabetes (T1D).¹

Data from the single-center, retrospective observational study revealed tirzepatide, a dual GLP-1/GIP agonist, was associated with significant reductions in hemoglobin A1c (HbA1c) and body weight among adults with T1D.

“A randomized controlled trial is needed to establish efficacy and safety of this drug in T1D,” wrote the investigative team led by Viral N. Shah, MD, a professor of endocrinology at the Indiana University School of Medicine and the director of diabetes clinical research at the IU Center for Diabetes and Metabolic Diseases.

The US Food and Drug Administration (FDA) first approved tirzepatide (Mounjaro) in May 2022 as an adjunct to diet and exercise for improving glycemic control among adults with type 2 diabetes (T2D).² Approval was granted based on data from the SURPASS program, showing 15 mg tirzepatide led to a 1.6% greater reduction in mean HbA1c versus placebo as a stand-alone therapy and a 1.5% greater reduction than placebo in combination with long-acting insulin.

In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with obesity or overweight and ≥1 weight-related condition.³ Across both the SURMOUNT-1 and SURMOUNT-2 trials, after 72-week treatment, those treated with once-weekly tirzepatide 5 mg, 10 mg, or 15 mg exhibited a statistically significant reduction in body weight compared to those who received placebo.

A recipient of both Priority Review and Fast Track designations, the approval represented the first weight management approval for a dual GLP-1/GIP agonist.

Within the current study, Shah and colleagues obtained data on HbA1c, weight, body mass index (BMI), and continuous glucose monitoring (CGM) from electronic health records at the initiation of tirzepatide among patients with T1D.¹ The same measures were collected at subsequent clinic visits over 8 months in the study population.

For the analysis, the primary outcomes were a reduction in HbA1c and a percent change in body weight. Then, secondary outcomes included the change in CGM metrics and BMI over 8 months from baseline. Of 26 adults included in the study, 54% were female, the mean age was 42 years, and the mean BMI was 36.7 ± 5.3 kg/m2.

Upon analysis, Shah and colleagues found a significant reduction in HbA1c with tirzepatide, by 0.45% at 3 months and 0.59% at 8 months. The findings also showed a significant reduction in body weight by 3.4%, 10.5%, and 10.1% at 3, 6, and 8 months after initiating tirzepatide treatment.

Meanwhile, the time-in-target range (TIR, 70-80 mg/dL) and time-in-tight-target range (TITR, 70-140 mg/dL) increased with tirzepatide treatment (TIR: +12.6%, P = .002; TITR, +10.7%, P = .0016). Results showed the time above range (TAR, >180 mg/dL) decreased at 3 months –12.6%, P = .002) at 3 months, with sustained changes over 8 months.

Shah and colleagues indicated tirzepatide was relatively safe and well-tolerated during the study period. Only 2 patients in the study population discontinued the medication during observation.

These results continue the growing evidence base suggesting the utility of GLP-1 agonist-based medications for people with T1D. A recent study reported the use of off-label semaglutide, another GLP-1 agonist, eliminated the need for mealtime insulin doses among 10 people with newly diagnosed T1D and allowed 70% to eliminate basal insulin use within 6 months.⁴

“We were definitely surprised by our findings and also quite excited. If these findings are borne out in larger studies over extended follow-up periods, it could possibly be the most dramatic change in treating T1D since the discovery of insulin in 1921,” said Paresh Dandona, MD, PhD, former chief of the Division of Endocrinology in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo.⁵

References

1. _{Akturk HK, Dong F, Snell-Bergeon JK, Karakus KE, Shah VN. Efficacy and Safety of Tirzepatide in Adults With Type 1 Diabetes: A Proof of Concept Observational Study. Journal of Diabetes Science and Technology. 2024;0(0). doi:10.1177/19322968231223991}
2. _{Campbell P. Tirzepatide (Mounjaro) wins FDA approval for type 2 diabetes. HCP Live. April 27, 2023. Accessed February 7, 2024. https://www.hcplive.com/view/tirzepatide-wins-fda-approval-for-type-2-diabetes.}
3. _{Campbell P. FDA approves Tirzepatide (Zepbound) for Chronic Weight Management. HCP Live. November 8, 2023. Accessed February 7, 2024. https://www.hcplive.com/view/fda-approves-tirzepatide-zepbound-chronic-weight-management.}
4. _{Campbell P. SEMAGLUTIDE could eliminate need for insulin in type 1 diabetes. HCP Live. October 3, 2023. Accessed February 7, 2024. https://www.hcplive.com/view/semaglutide-could-eliminate-need-for-insulin-in-type-1-diabetes.}
5. _{University at Buffalo. After treatment with semaglutide, newly diagnosed Type 1 diabetes patients needed little or no insulin. EurekAlert. September 6, 2023. Accessed September 6, 2023. https://www.eurekalert.org/news-releases/1000574.}