» Articles » PMID: 37954886

Evaluating Glycemic Control Efficacy and Safety of the Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis

Overview
Publisher Dove Medical Press
Specialty Endocrinology
Date 2023 Nov 13
PMID 37954886
Authors
Affiliations
Soon will be listed here.
Abstract

Introduction: Diabetes Mellitus (DM) is a significant global health concern, with Type 2 DM (T2DM) being highly prevalent. Glucagon-Like Peptide 1 receptor agonists (GLP-1RA), such as Danuglipron, offer potential benefits in T2DM management. This meta-analysis examines the safety and efficacy of Danuglipron, focusing on adverse outcomes and glycemic parameters.

Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane Library for RCTs involving Danuglipron till August 2023, following PRISMA guidelines. The Cochrane risk-of-bias tool was used for quality assessment. Adverse outcomes (diarrhea, nausea, vomiting, headache, decreased appetite, dyspepsia, dizziness) and glycemic parameters like changes in HbA1C, fasting plasma glucose (FPG), and body weight were analyzed.

Results: Four RCTs published from 2021 to 2023 were included. Both doses of Danuglipron were associated with diarrhea (RR=2.66, 90% CI: 1.32 to 5.35, p=0.02), nausea (RR=5.5, 90% CI: 3.4 to 8.88, p<0.00001), and vomiting (RR=5.98, 90% CI: 2.93 to 12.23, p=0.0001). The 120mg dose showed decreased appetite (RR=3.46, 90% CI: 1.57 to 7.62, p=0.01), dyspepsia (RR=4.04, 90% CI: 1.93 to 8.43, p=0.002), and dizziness (RR=5.08, 90% CI: 1.45 to 17.82, p=0.03). Reductions in HbA1C (SMD -1.09, 90% CI -1.39 to -0.8, p < 0.00001), FPG (SMD -1.10, 90% CI -1.46 to -0.75, p < 0.00001), and body weight (SMD -1.08, 90% CI -1.42 to -0.74, p < 0.00001) were observed for both doses.

Conclusion: Danuglipron demonstrates potential for glycemic control and weight reduction in T2DM. Adverse outcomes include diarrhea, nausea, vomiting, and decreased appetite, with dose-related effects. Clinicians must weigh benefits against side effects when considering Danuglipron for T2DM management.

Citing Articles

Insights into the Roles of GLP-1, DPP-4, and SGLT2 at the Crossroads of Cardiovascular, Renal, and Metabolic Pathophysiology.

Gaggini M, Sabatino L, Suman A, Chatzianagnostou K, Vassalle C Cells. 2025; 14(5).

PMID: 40072115 PMC: 11898734. DOI: 10.3390/cells14050387.


Non-clinical and first-in-human characterization of ECC5004/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist.

Haggag A, Butcher L, Pagnussat S, Davies G, Lundqvist S, Wang W Diabetes Obes Metab. 2024; 27(2):551-562.

PMID: 39495140 PMC: 11701199. DOI: 10.1111/dom.16047.


GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management.

Holst J Nat Metab. 2024; 6(10):1866-1885.

PMID: 39160334 DOI: 10.1038/s42255-024-01113-9.


Evaluating the effectiveness and safety of various Tirzepatide dosages in the management of Type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials.

Rangwala H, Fatima H, Ali M, Mustafa M, Shafique M, Rangwala B J Diabetes Metab Disord. 2024; 23(1):1199-1222.

PMID: 38932909 PMC: 11196572. DOI: 10.1007/s40200-024-01412-8.


New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions.

Chatzianagnostou K, Gaggini M, Suman Florentin A, Simonini L, Vassalle C Int J Mol Sci. 2024; 25(11).

PMID: 38892417 PMC: 11173177. DOI: 10.3390/ijms25116218.


References
1.
Thomas M, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K . Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2020; 106(2):388-396. PMC: 7823251. DOI: 10.1210/clinem/dgaa863. View

2.
Nauck M, Quast D, Wefers J, Meier J . GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2020; 46:101102. PMC: 8085572. DOI: 10.1016/j.molmet.2020.101102. View

3.
Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. PMC: 8005924. DOI: 10.1136/bmj.n71. View

4.
Hartman M, Sanyal A, Loomba R, Wilson J, Nikooienejad A, Bray R . Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes. Diabetes Care. 2020; 43(6):1352-1355. PMC: 7245348. DOI: 10.2337/dc19-1892. View

5.
Niman S, Hardy J, Goldfaden R, Reid J, Sheikh-Ali M, Sutton D . A Review on the Efficacy and Safety of Oral Semaglutide. Drugs R D. 2021; 21(2):133-148. PMC: 8206300. DOI: 10.1007/s40268-021-00341-8. View