Evaluation of GLP-1 Receptor Agonists in Combination With Multiple Daily Insulin Injections for Type 2 Diabetes

Sassenrath, Kimberly; Phillips, Beth Bryles; Stone, Rebecca H.

doi:10.1177/08971900211010678

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…Similar findings were made in the study by Sassenrath et al, which showed that the combination of insulin and a GLP-1RA improves blood glucose control and reduces the dose of insulin required, without increasing the incidence of hypoglycemia. 46 …”

Section: Discussionmentioning

confidence: 99%

Liraglutide in Combination with Insulin Has a Superior Therapeutic Effect to Either Alone on Fracture Healing in Diabetic Rats

Liu¹,

Tian²,

Hu³

et al. 2023

DMSO

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Purpose Fractures in patients with type 2 diabetes mellitus are at a high risk of delayed union or non-union. Previous studies have shown a protective effect of liraglutide on bone. In the present study, we aimed to investigate the effects of a combination of liraglutide and insulin on fracture healing in a rat model of diabetes and the mechanisms involved. Materials and Methods Closed femoral mid-shaft fractures were established in male Sprague-Dawley rats with or without diabetes mellitus, and the diabetic rats were administered insulin and/or liraglutide. Six weeks after femoral fracture, the femoral callus was evaluated by immunohistochemistry, histology, and micro-computed tomography. Additionally, the effects of liraglutide on high-glucose-stimulated MC3T3-E1 cells were analyzed by Western blotting. Results Micro-computed tomography and safranin O/fast green staining showed that fracture healing was delayed in the diabetic rats, and this was accompanied by much lower expression of osteogenic markers and greater osteoclast activity. However, treatment with insulin and/or liraglutide prevented these changes. Liraglutide in combination with insulin treatment resulted in lower blood glucose concentrations and significantly higher osteocalcin (OCN) and collagen I (Col I) expression six weeks following fracture. Western blot analysis showed that liraglutide prevented the low expression of the bone morphogenetic protein-2, osterix/SP7, OCN, Col I, and β-catenin in high-glucose-stimulated MC3T3-E1 cells. Conclusion These results demonstrate that insulin and/or liraglutide promotes bone fracture healing in the DF model. The combination was more effective than either single treatment, which may be because of the two drugs’ additive effects on the osteogenic ability of osteoblast precursors.

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Section: Discussionmentioning

confidence: 99%

Liraglutide in Combination with Insulin Has a Superior Therapeutic Effect to Either Alone on Fracture Healing in Diabetic Rats

Liu¹,

Tian²,

Hu³

et al. 2023

DMSO

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“…[6][7][8][9] In addition, basal insulin and GLP-1RA have a synergistic effect that can further improve blood glucose control and reduce the adverse side effects of each ingredient, such as weight gain, hypoglycemia and gastrointestinal symptoms. [29][30][31] Therefore, the combination of weekly insulin and weekly GLP-1RA is a promising strategy. Future studies could explore the feasibility of this combination.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of once-weekly basal insulin versus once-daily basal insulin in patients with type 2 diabetes: A systematic review and meta-analysis

Wang,

Xiao,

Liang

et al. 2023

Medicine

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Background: Once-weekly insulin is expected to improve treatment compliance and durability and lead to better glycemic control. Several clinical trials on once-weekly insulin have recently been published. We conducted a systematic review and meta-analysis to investigate the efficacy and safety of once-weekly insulin versus once-daily insulin in type 2 diabetes (T2D). Methods: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (From January 1, 1946 to May 9, 2023). All randomized trials comparing weekly versus daily insulin in T2D were eligible for inclusion. Data analysis was performed using STATA 17.0 software (Stata Corporation, College Station, TX). The main outcomes and indexes included reduction in Hemoglobin A1c (HbA1c), fasting plasma glucose and bodyweight, proportion of patients achieving HbA1c < 7%, time-in-range 70 to 180 mg/dL and adverse events. Results: This systematic review and meta-analysis included 7 randomized controlled studies involving 2391 patients (1347 receiving 1-week insulin and 1044 receiving 1-day insulin). Once-weekly insulin was not inferior to once-daily insulin in HbA1c change [estimated treatment difference (ETD) = −0.05; 95% confidence intervals (CI): −0.14 to 0.04), HbA1c < 7% (odds ratio = 1.14; 95% CI: 0.87–1.50), fasting plasma glucose (ETD = 0.09; 95% CI: −0.19 to 0.36) and body weight loss (ETD = 0.27; 95% CI: −0.36 to 0.91). In terms of time-in-range 70 to 180 mg/dL, weekly insulin was superior to daily insulin (MTD = 3.84; 95% CI: 1.55–6.08). Icodec was associated with higher incidence of all adverse events (odds ratio = 1.20; 95% CI: 1.03–1.48; P = .024), but did not result in high risk of serious and severe adverse events. Moreover, icodec and Basal Insulin Fc did not result in higher incidence of hypoglycemia compared with insulin daily. Conclusion: Our meta-analysis found that insulin weekly was well tolerated and effective for glycemic control. Once-weekly insulin was not inferior to once-daily insulin in both efficacy and safety in T2D.

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“…A recent systematic review found that the addition of GLP-1 RA to multiple daily insulin injections reduced A1c and total daily insulin doses without increasing hypoglycemia frequency or other adverse events. 14 Clinicians may be more prone to pre-emptively reducing insulin doses when starting therapy with semaglutide to mitigate hypoglycemia risk or simplify complex medication regimens, as current literature suggests that semaglutide is a more potent GLP-1 RA compared to liraglutide. 8,9 Importantly, the baseline insulin dose per day was higher in the semaglutide group vs. the liraglutide group which may explain the finding of larger reductions in insulin doses seen in the semaglutide group.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Effectiveness of Liraglutide vs Semaglutide in a Veteran Population

Rana

Britnell

Gilbertson

et al. 2022

Journal of Pharmacy Practice

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Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed medications for patients with type 2 diabetes mellitus (T2DM) based on cardiovascular benefits. Objective This study aimed to evaluate efficacy and tolerability of once daily liraglutide vs once weekly semaglutide on T2DM in a Veteran population. Methods This was a retrospective, single-center, cohort study that included T2DM patients with a prescription for liraglutide or semaglutide between September 1st, 2019, and September 30th, 2020. Patients between groups were matched based on age and insulin use at baseline. The primary endpoint was the difference in hemoglobin A1c (A1c) between the most recent A1c in the study period and baseline A1c obtained prior to GLP-1 RA initiation. Results There were 154 patients included in the study. While mean reduction in A1c was numerically higher in the liraglutide group (−1.1% vs. −.8%), this was not statistically significant ( P = .22). The proportion of patients achieving A1c < 7%, < 8%, < 9%, or their patient-specific A1c goal did not differ between groups. Although baseline total daily doses of insulin were higher in the semaglutide group, these patients had numerically greater reductions in total daily dose of insulin and weight from baseline; however, no statistical difference was observed. Adverse drug reactions were more common in the semaglutide group (n = 14 vs. 9), leading to higher discontinuation rates as well (n = 11 vs. 8). Conclusion The results of this study indicate no difference between liraglutide and semaglutide in terms of A1c-lowering potential, but it provides insights into key considerations for the Veteran population.

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Evaluation of GLP-1 Receptor Agonists in Combination With Multiple Daily Insulin Injections for Type 2 Diabetes

Cited by 7 publications

References 22 publications

Liraglutide in Combination with Insulin Has a Superior Therapeutic Effect to Either Alone on Fracture Healing in Diabetic Rats

Liraglutide in Combination with Insulin Has a Superior Therapeutic Effect to Either Alone on Fracture Healing in Diabetic Rats

Efficacy and safety of once-weekly basal insulin versus once-daily basal insulin in patients with type 2 diabetes: A systematic review and meta-analysis

Comparison of the Effectiveness of Liraglutide vs Semaglutide in a Veteran Population

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