Original Research

Assessment of Glucagon-like Peptide-1 Receptor Agonists in Veterans Taking Basal/Bolus Insulin Regimens

Fed Pract. 2022 November;39(5):S18-S23 | doi:10.12788/fp.0317

References

1. American Diabetes Association. Statistics about diabetes. Accessed August 9, 2022. http://www.diabetes.org/diabetes-basics/statistics

2. US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. VA research on: diabetes. Updated January 15, 2021. Accessed August 9, 2022. https://www.research.va.gov/topics/diabetes.cfm

3. Federal Practitioner. Federal Health Care Data Trends 2017, Diabetes mellitus. Accessed August 9, 2022. https://www.fedprac-digital.com/federalpractitioner/data_trends_2017?pg=20#pg20

4. American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2022. Diabetes Care. 2022;45(suppl 1):S125-S143. doi:10.2337/dc22-S009

5. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2019 executive summary. Endocr Pract. 2019;25(1):69-100. doi:10.4158/CS-2018-0535

6. St Onge E, Miller S, Clements E, Celauro L, Barnes K. The role of glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes. J Transl Int Med. 2017;5(2):79-89. Published 2017 Jun 30. doi:10.1515/jtim-2017-0015

7. Almandoz JP, Lingvay I, Morales J, Campos C. Switching between glucagon-like peptide-1 receptor agonists: rationale and practical guidance. Clin Diabetes. 2020;38(4):390-402. doi:10.2337/cd19-0100

8. Davies ML, Pham DQ, Drab SR. GLP1-RA add-on therapy in patients with type 2 diabetes currently on a bolus containing insulin regimen. Pharmacotherapy. 2016;36(8):893-905. doi:10.1002/phar.1792

9. Rosenstock J, Guerci B, Hanefeld M, et al. Prandial options to advance basal insulin glargine therapy: testing lixisenatide plus basal insulin versus insulin glulisine either as basal-plus or basal-bolus in type 2 diabetes: the GetGoal Duo-2 Trial Investigators. Diabetes Care. 2016;39(8):1318-1328. doi:10.2337/dc16-0014

10. Levin PA, Mersey JH, Zhou S, Bromberger LA. Clinical outcomes using long-term combination therapy with insulin glargine and exenatide in patients with type 2 diabetes mellitus. Endocr Pract. 2012;18(1):17-25. doi:10.4158/EP11097.OR

11. Yoon NM, Cavaghan MK, Brunelle RL, Roach P. Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. Clin Ther. 2009;31(7):1511-1523. doi:10.1016/j.clinthera.2009.07.021

12. Weissman PN, Carr MC, Ye J, et al. HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea. Diabetologia. 2014;57(12):2475-2484. doi:10.1007/s00125-014-3360-3

13. Gyorffy JB, Keithler AN, Wardian JL, Zarzabal LA, Rittel A, True MW. The impact of GLP-1 receptor agonists on patients with diabetes on insulin therapy. Endocr Pract. 2019;25(9):935-942. doi:10.4158/EP-2019-0023

14. Seino Y, Kaneko S, Fukuda S, et al. Combination therapy with liraglutide and insulin in Japanese patients with type 2 diabetes: a 36-week, randomized, double-blind, parallel-group trial. J Diabetes Investig. 2016;7(4):565-573. doi:10.1111/jdi.12457

15. Optum. Tanzeum (albiglutide)–drug discontinuation. Published 2017. Accessed August 15, 2022. https://professionals.optumrx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-recalls-shortages/drugwithdrawal_tanzeum_2017-0801.pdf

16. Chun JH, Butts A. Long-acting GLP-1RAs: an overview of efficacy, safety, and their role in type 2 diabetes management. JAAPA. 2020;33(8):3-18. doi:10.1097/01.JAA.0000669456.13763.bd

17. Ozempic semaglutide injection. Prescribing information. Novo Nordisk; 2022. Accessed August 9, 2022. https://www.novo-pi.com/ozempic.pdf

18. Victoza liraglutide injection. Prescribing information. Novo Nordisk; 2021. Accessed August 9, 2022. https://www.novo-pi.com/victoza.pdf

Methods

This study was a retrospective, electronic health record review of all patients on basal and bolus insulin regimens who received additional therapy with a GLP-1 RA at Veteran Health Indiana in Indianapolis from September 1, 2015, to June 30, 2019. Patients meeting inclusion criteria served as their own control. The primary outcome was change in HbA_1c at 3, 6, 12, 18, and 24 months after initiation of the GLP-1 RA. Secondary outcomes included change in weight and TDD of insulin at 3, 6, 12, 18, and 24 months after the initiation of the GLP-1 RAs and incidence of patient-reported or laboratory-confirmed hypoglycemia and other AEs.

Patients were included if they were aged ≥ 18 years with a diagnosis of T2DM, had concomitant prescriptions for both a basal insulin (glargine, detemir, or NPH) and a bolus insulin (aspart, lispro, or regular) before receiving add-on therapy with a GLP-1 RA (exenatide, liraglutide, albiglutide, lixisenatide, dulaglutide, or semaglutide) from September 1, 2015, to June 30, 2019, and had baseline and subsequent HbA_1c measurements available in the electronic health record. Patients were excluded if they had a diagnosis of type 1 DM (T1DM), were followed by an outside clinician for DM care, or if the GLP-1 RA was discontinued before subsequent HbA_1c measurement. The study protocol was approved by the Research and Development Office of Veteran Health Indiana, and the project was deemed exempt from review by the Indiana University Institutional Review Board due to the retrospective nature of the study.

Data analysis was performed using Excel. Change from baseline for each interval was computed, and 1 sample t tests (2-tailed) compared change from baseline to no change. Due to the disparity in the number of patients with data available at each of the time intervals, a mean plot was presented for each group of patients within each interval, allowing mean changes in individual groups to be observed over time.

Results

One hundred twenty-three subjects met inclusion criteria; 16 patients were excluded due to GLP-1 RA discontinuation before follow-up measurement of HbA_1c; 14 were excluded due to patients being managed by a clinician outside of the facility; 1 patient was excluded for lack of documentation regarding baseline and subsequent insulin doses. Ninety-two patient charts were reviewed. Participants had a mean age of 64 years, 95% were male, and 89% were White. Mean baseline HbA_1c was 9.2%, mean body mass index was 38.9, and the mean TDD of insulin was 184 units.

Mean duration of DM was 10 years, and mean use of basal/bolus insulin regimen was 6.1 years. Most participants (91%) used an insulin regimen containing insulin glargine and insulin aspart; the remaining participants used insulin detemir and insulin aspart. Semaglutide and liraglutide were the most commonly used GLP-1 RAs (44% and 39%, respectively) (Table 1).

Since some patients switched between GLP-1 RAs throughout the study and there was variation in timing of laboratory and clinic follow-up,

a different number of patient charts were available for review at each period (Table 2). Glycemic control was significantly improved at all time points when compared with baseline, but over time the benefit declined. The mean change in HbA_1c was −1.1% (95% CI, −1.3 to −0.8; P < .001) at 3 months; −1.0% (95% CI, −1.3 to −0.7; P < .001) at 6 months; −0.9% (95% CI, −1.3 to −0.6; P < .001) at 12 months; −0.9% (95% CI, −1.4 to −0.3; P = .002) at 18 months; and −0.7% (95% CI, −1.4 to 0.1; P = .07) at 24 months (Figure 1).

Mean weight decreased from baseline −2.7 kg (95% CI, −3.7 to −1.6; P < .001); −4.4 kg (95% CI −5.7 to −3.2; P < .001) at 6 months; −3.9 kg (95% CI −6.0 to −1.9; P < .001) at 12 months; −4.7 kg (95% CI −6.7 to −2.6; P < .001) at 18 months; and −2.8 kg (95% CI, −5.9 to 0.3; P = .07) at 24 months (Figure 2).

Mean TDD decreased at 3 months −12 units (95% CI, −19 to −5; P < .001); −18 units (95% CI, −27 to −9; P < .001) at 6 months; −14 units (95% CI, −24 to −5; P = .004) at 12 months; −9 units (95% CI, −21 to 3; P = .15) at 18 months; and −18 units (95% CI, −43 to 5 units; P = .12) at 24 months (Figure 3).

The most common AEs were hypoglycemia (30%), diarrhea (11%), nausea (4%), and abdominal pain (3%).

References

1. American Diabetes Association. Statistics about diabetes. Accessed August 9, 2022. http://www.diabetes.org/diabetes-basics/statistics

2. US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. VA research on: diabetes. Updated January 15, 2021. Accessed August 9, 2022. https://www.research.va.gov/topics/diabetes.cfm

3. Federal Practitioner. Federal Health Care Data Trends 2017, Diabetes mellitus. Accessed August 9, 2022. https://www.fedprac-digital.com/federalpractitioner/data_trends_2017?pg=20#pg20

4. American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2022. Diabetes Care. 2022;45(suppl 1):S125-S143. doi:10.2337/dc22-S009

5. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2019 executive summary. Endocr Pract. 2019;25(1):69-100. doi:10.4158/CS-2018-0535

6. St Onge E, Miller S, Clements E, Celauro L, Barnes K. The role of glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes. J Transl Int Med. 2017;5(2):79-89. Published 2017 Jun 30. doi:10.1515/jtim-2017-0015

7. Almandoz JP, Lingvay I, Morales J, Campos C. Switching between glucagon-like peptide-1 receptor agonists: rationale and practical guidance. Clin Diabetes. 2020;38(4):390-402. doi:10.2337/cd19-0100

8. Davies ML, Pham DQ, Drab SR. GLP1-RA add-on therapy in patients with type 2 diabetes currently on a bolus containing insulin regimen. Pharmacotherapy. 2016;36(8):893-905. doi:10.1002/phar.1792

9. Rosenstock J, Guerci B, Hanefeld M, et al. Prandial options to advance basal insulin glargine therapy: testing lixisenatide plus basal insulin versus insulin glulisine either as basal-plus or basal-bolus in type 2 diabetes: the GetGoal Duo-2 Trial Investigators. Diabetes Care. 2016;39(8):1318-1328. doi:10.2337/dc16-0014

10. Levin PA, Mersey JH, Zhou S, Bromberger LA. Clinical outcomes using long-term combination therapy with insulin glargine and exenatide in patients with type 2 diabetes mellitus. Endocr Pract. 2012;18(1):17-25. doi:10.4158/EP11097.OR

11. Yoon NM, Cavaghan MK, Brunelle RL, Roach P. Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. Clin Ther. 2009;31(7):1511-1523. doi:10.1016/j.clinthera.2009.07.021

12. Weissman PN, Carr MC, Ye J, et al. HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea. Diabetologia. 2014;57(12):2475-2484. doi:10.1007/s00125-014-3360-3

13. Gyorffy JB, Keithler AN, Wardian JL, Zarzabal LA, Rittel A, True MW. The impact of GLP-1 receptor agonists on patients with diabetes on insulin therapy. Endocr Pract. 2019;25(9):935-942. doi:10.4158/EP-2019-0023

14. Seino Y, Kaneko S, Fukuda S, et al. Combination therapy with liraglutide and insulin in Japanese patients with type 2 diabetes: a 36-week, randomized, double-blind, parallel-group trial. J Diabetes Investig. 2016;7(4):565-573. doi:10.1111/jdi.12457

15. Optum. Tanzeum (albiglutide)–drug discontinuation. Published 2017. Accessed August 15, 2022. https://professionals.optumrx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-recalls-shortages/drugwithdrawal_tanzeum_2017-0801.pdf

16. Chun JH, Butts A. Long-acting GLP-1RAs: an overview of efficacy, safety, and their role in type 2 diabetes management. JAAPA. 2020;33(8):3-18. doi:10.1097/01.JAA.0000669456.13763.bd

17. Ozempic semaglutide injection. Prescribing information. Novo Nordisk; 2022. Accessed August 9, 2022. https://www.novo-pi.com/ozempic.pdf

18. Victoza liraglutide injection. Prescribing information. Novo Nordisk; 2021. Accessed August 9, 2022. https://www.novo-pi.com/victoza.pdf

Assessment of Glucagon-like Peptide-1 Receptor Agonists in Veterans Taking Basal/Bolus Insulin Regimens

References

Methods

Results

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