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Dr Rida Rizvi
Dr Ashutosh Roy
Dr Renju Ravi
Dr Jyothi Vybhavi V S


Diabetes, GLP-1, DPP-4, Blood sugar, Receptor


Introduction: Decisions on balancing use of GLP-1 receptor agonists or DPP-4 inhibitors depend on various factors like patient's own characteristics and choice, in addition to medical background. GLP- 1 receptor agonists and DPP-4 inhibitor are a class of medications that work on incretin system to normoglycemia.

Aims and Objectives: To compare the effectiveness of drugs for the treatment of type 2 diabetes: GLP-1 receptor agonists Vs DPP-4 inhibitors.

Methods: A search of the MEDLINE databases restricted to human clinical trials using the search terms 'GLP-1RA' or 'DPP-4 inhibitor' produced seven direct comparative studies and one post hoc analysis all comparing a GLP-1RA with sitagliptin. The effectiveness and safety of GLP-1RAs and DPP-4 inhibitors in T2D patients was assessed by use of a variety of tools including research studies, treatment algorithms, product prescribing information, and personal clinical experience.

Results: For GLP-1RAs, direct clinical trials showed superior control of blood sugar levels, weight reduction, and general drug approach compared to sitagliptin: the DPP-4 inhibitions through these medications, rarely, consumers experience side effects like nausea. However, with a proper education and threat, dosage increase could manage it, though. The nausea is momentarily. From a nutshell, the existing treatment guidelines make an increment over metformin medication with a switch to an incretin-based agent for further reducing the cardiovascular risk in those patients who are already on the treatment, but this use remains restricted in some countries.

Conclusion: GLP-1RAs give a better glucose control and weight loss in T2D than DPP-4 inhibitors. Alternatives are DPP-4 inhibitors instead of GLP-1RAs in situations of no prominent weight changes, when formulation by mouth is necessary or only well-tolerated GLP-1RAs are available.

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1. A. M. Ahmed, “History of diabetes mellitus,” Saudi Med J, vol. 23, no. 4, pp. 373–378, 2002, [Online]. Available: https://www.researchgate.net/
2. C. O. Osborn, “Type 1 and Type 2 Diabetes: What’s the Difference?,” 2022, [Online]. Available: https://www.healthline.com/
3. M. Patlak, “New Weapons to Combat an Ancient Disease,” FASEB J, vol. 16, no. 14, 2002, [Online]. Available: https://www.margiepatlak.com/
4. S. Liu et al., “Neutrophil-to-lymphocyte ratio is associated with diabetic peripheral neuropathy in type 2 diabetes patients,” Diabetes Res. Clin. Pract., vol. 130, pp. 90–97, Aug. 2017, doi: 10.1016/j.diabres.2017.05.008.
5. S. Tsalamandris et al., “The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives,” Eur. Cardiol. Rev., vol. 14, no. 1, pp. 50–59, Apr. 2019, doi: 10.15420/ecr.2018.33.1.
6. A. D. Association, “Diagnosis and Classification of Diabetes Mellitus,” Diabetes Care, vol. 27, no. suppl_1, pp. s5–s10, Jan. 2004, doi: 10.2337/diacare.27.2007.S5.
7. C. Weyer, C. Bogardus, D. M. Mott, and R. E. Pratley, “The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus,” J. Clin. Invest., vol. 104, no. 6, pp. 787–794, Sep. 1999, doi: 10.1172/JCI7231.
8. M. Stumvoll, B. J. Goldstein, and T. W. van Haeften, “Type 2 diabetes: principles of pathogenesis and therapy,” Lancet, vol. 365, no. 9467, pp. 1333–1346, Apr. 2005, doi: 10.1016/S0140-6736(05)61032-X.
9. S. Chatterjee, K. Khunti, and M. J. Davies, “Type 2 diabetes,” Lancet, vol. 389, no. 10085, pp. 2239–2251, Jun. 2017, doi: 10.1016/S0140-6736(17)30058-2.
10. B. Zhou et al., “Worldwide trends in diabetes since 1980: a pooled analysis of 751 population- based studies with 4·4 million participants,” Lancet, vol. 387, no. 10027, pp. 1513–1530, Apr. 2016, doi: 10.1016/S0140-6736(16)00618-8.

11. M. Prelipcean, “Behind the counter: Glucagon-like peptide-1 receptor agonists for type 2 diabetes,” 2020, [Online]. Available: https://www.medicalnewstoday.com/
12. W. Latif, K. J. Lambrinos, and R. Rodriguez., “Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs),” 2023, [Online]. Available: https://www.ncbi. nlm.nih.gov/
13. B. Cervoni, “GLP-1 Receptor Agonists for Type 2 Diabetes,” 2023, [Online]. Available: https://www.verywellhealth.com/
14. S. W. Lim, J. Z. Jin, L. Jin, J. Jin, and C. Li, “Role of dipeptidyl peptidase-4 inhibitors in new- onset diabetes after transplantation,” Korean J. Intern. Med., vol. 30, no. 6, pp. 759–770, Oct. 2015, doi: 10.3904/kjim.2015.30.6.759.
15. B. Charbonnel, A. Karasik, J. Liu, M. Wu, and G. Meininger, “Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone,” Diabetes Care, vol. 29, no. 12, pp. 2638–2643, Dec. 2006, doi: 10.2337/dc06-0706.
16. E. Bosi, R. P. Camisasca, C. Collober, E. Rochotte, and A. J. Garber, “Effects of Vildagliptin on Glucose Control Over 24 Weeks in Patients With Type 2 Diabetes Inadequately Controlled With Metformin,” Diabetes Care, vol. 30, no. 4, pp. 890–895, Apr. 2007, doi: 10.2337/dc06-1732.
17. R. A. DeFronzo et al., “The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone,” Diabetes Care, vol. 32, no. 9, pp. 1649–1655, Sep. 2009, doi: 10.2337/dc08-1984.
18. K. Hermansen, M. Kipnes, E. Luo, D. Fanurik, H. Khatami, and P. Stein, “Efficacy and safety of the dipeptidyl peptidase‐4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin,” Diabetes, Obes. Metab., vol. 9, no. 5, pp. 733–745, Sep. 2007, doi: 10.1111/j.1463-1326.2007.00744.x.
19. J. Rosenstock, R. Brazg, P. J. Andryuk, K. Lu, and P. Stein, “Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study,” Clin. Ther., vol. 28, no. 10, pp. 1556–1568, Oct. 2006, doi: 10.1016/j.clinthera
20. A. J. Garber, A. Schweizer, M. A. Baron, E. Rochotte, and S. Dejager, “Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo‐controlled study*,” Diabetes, Obes. Metab., vol. 9, no. 2, pp. 166–174, Mar. 2007, doi: 10.1111/j.1463-1326.2006.00684.x.
21. L. Kennedy and J. A. Davidson, “Advances in therapy for type 2 diabetes: GLP–1 receptor agonists and DPP–4 inhibitors,” Cleve. Clin. J. Med., vol. 76, no. 12 suppl 5, pp. S28–S38, Dec. 2009, doi: 10.3949/ccjm.76.s5.05.
22. J. Gerich, “DPP-4 inhibitors: What may be the clinical differentiators?,” Diabetes Res. Clin. Pract., vol. 90, no. 2, pp. 131–140, Nov. 2010, doi: 10.1016/j.diabres.2010.07.006.
23. R. A. DeFronzo, T. Okerson, P. Viswanathan, X. Guan, J. H. Holcombe, and L. MacConell, “Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study,” Curr. Med. Res. Opin., vol. 24, no. 10, pp. 2943–2952, Oct. 2008, doi: 10.1185/03007990802418851.
24. J. K. Berg, S. K. Shenouda, C. R. Heilmann, A. L. Gray, and J. H. Holcombe, “Effects of exenatide twice daily versus sitagliptin on 24‐h glucose, glucoregulatory and hormonal measures: a randomized, double‐blind, crossover study,” Diabetes, Obes. Metab., vol. 13, no. 11, pp. 982– 989, Nov. 2011, doi: 10.1111/j.1463-1326.2011.01428.x.
25. R. M. Bergenstal et al., “Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial,” Lancet, vol. 376, no. 9739, pp. 431–439, Aug. 2010, doi: 10.1016/S0140-
26. C. Wysham et al., “DURATION‐2: efficacy and safety of switching from maximum daily

sitagliptin or pioglitazone to once‐weekly exenatide,” Diabet. Med., vol. 28, no. 6, pp. 705–714, Jun. 2011, doi: 10.1111/j.1464-5491.2011.03301.x.
27. R. E. Pratley et al., “Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open- label trial,” Lancet, vol. 375, no. 9724, pp. 1447–1456, Apr. 2010, doi: 10.1016/S0140-6736
28. R. Pratley et al., “One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial,” Int. J. Clin. Pract., vol. 65, no. 4, pp. 397–407, Apr. 2011, doi: 10.1111/j.1742-1241.2011.02656.x.
29. R. E. Pratley et al., “Efficacy and Safety of Switching From the DPP-4 Inhibitor Sitagliptin to the Human GLP-1 Analog Liraglutide After 52 Weeks in Metformin-Treated Patients With Type 2 Diabetes,” Diabetes Care, vol. 35, no. 10, pp. 1986–1993, Oct. 2012, doi: 10.2337/dc11-2113.
30. M. Davies, R. E. Pratley, E. Montanya, and A. Thomsen, “Liraglutide Reduces A1c to a Greater Extent Than Sitagliptin Regardless of Baseline A1c Levels,” 2010, [Online]. Available: https://www.researchgate.net/
31. A. B. King et al., “Liraglutide Achieves A1C Targets More often than Sitagliptin or Exenatide when Added to Metformin in Patients with Type 2 Diabetes and a Baseline A1C <8.0%,” Endocr. Pract., vol. 19, no. 1, pp. 64–72, Jan. 2013, doi: 10.4158/EP12232.OR.
32. M. J. Abrahamson et al., “Aace Comprehensive Diabetes Management Algorithm 2013,” Endocr. Pract., vol. 19, no. 2, pp. 327–336, Mar. 2013, doi: 10.4158/endp.19.2.a38267720403k242.
33. S. E. Inzucchi et al., “Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach,” Diabetes Care, vol. 35, no. 6, pp. 1364–1379, Jun. 2012, doi: 10.2337/dc12-0413.
34. N. I. for H. and C. Excellence, “Clinical guideline 87, the management of type 2 diabetes.,” 2009, [Online]. Available: http://www.nice.org.uk/nicemedia/live/12165/44320/44320.pdf
35. N. I. for H. and C. Excellence, “Final appraisal determination: Liraglutide for the treatment of type 2 diabetes mellitus.,” 2010, [Online]. Available: http://www.nice.org.uk/nicemedia
36. H. W. Rodbard et al., “Statement by an American Association of Clinical Endocrinologists/ American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control,” Endocr. Pract., vol. 15, no. 6, pp. 540–559, Sep. 2009, doi: 10.4158/EP.15.6.540.
37. Sanofi-aventis., “Lixisenatide SPC: Lixisenatide summary of product characteristics.,” 2013, [Online]. Available: https://ec.europa.eu/health/documents/community-register/2013/201302 01125120/anx_125120_en.pdf
38. A. Pharmaceuticals, “Byetta SPC,” 2013.
39. N. Nordisk, “Victoza SPC,” 2012, [Online]. Available: http://www.ema.europa.eu/docs/en_ GB/document_library/EPAR_-_Product_Information/human/000698/WC500051845.pdf
40. N. Nordisk., “Victoza PI,” 2024, [Online]. Available: http://www.novo-pi.com/victoza.pdf
41. A. Pharmaceuticals, “Bydureon PI,” 2024, [Online]. Available: http://documents.bydureon.com
42. A. Pharmaceuticals, “Bydureon SPC,” 2024, [Online]. Available: http://www.ema.europa.eu
43. A. Pharmaceuticals, “Byetta PI,” 2024, [Online]. Available: http://documents.byetta. com/ Byetta_PI.pdf
44. M. Sharp and D. Corp, “Januvia SPC,” 2024, [Online]. Available: http://www.ema.europa. eu/docs/en_GB/document_library/EPAR_-
45. B.-M. Squibb, “Onglyza SPC,” 2024, [Online]. Available: http://www.ema.europa.eu/docs/en_ GB/document_library/EPAR_-_Product_Information/human/001039/WC500044316.pdf

46. B.-M. Squibb, “Onglyza PI,” 2024, [Online]. Available: http://packageinserts.bms.com
47. Novartis, “Galvus SPC,” 2024, [Online]. Available: http://www.ema.europa.eu/docs/en_ GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf
48. I. Boehringer Ingelheim Pharmaceuticals, “Trajenta SPC.,” 2024, [Online]. Available: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
49. I. Boehringer Ingelheim Pharmaceuticals, “Trajenta PI,” 2024, [Online]. Available: http://bidocs.boehringer- ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Inf ormation/PIs/Tradjenta/Tradjenta.pdf
50. K. Nakatani et al., “Drug-induced generalized skin eruption in a diabetes mellitus patient receiving a dipeptidyl peptidase-4 inhibitor plus metformin,” Diabetes Ther., 2012, doi: 10.1007/s13300-012-0014-7.
51. M. A. Nauck, “A Critical Analysis of the Clinical Use of Incretin-Based Therapies,” Diabetes Care, vol. 36, no. 7, pp. 2126–2132, Jul. 2013, doi: 10.2337/dc12-2504.
52. R. A. Noel, D. K. Braun, R. E. Patterson, and G. L. Bloomgren, “Increased Risk of Acute Pancreatitis and Biliary Disease Observed in Patients With Type 2 Diabetes,” Diabetes Care, vol. 32, no. 5, pp. 834–838, May 2009, doi: 10.2337/dc08-1755.
53. A. E. Butler, M. Campbell-Thompson, T. Gurlo, D. W. Dawson, M. Atkinson, and P. C. Butler, “Marked Expansion of Exocrine and Endocrine Pancreas With Incretin Therapy in Humans With Increased Exocrine Pancreas Dysplasia and the Potential for Glucagon-Producing Neuroendocrine Tumors,” Diabetes, vol. 62, no. 7, pp. 2595–2604, Jul. 2013, doi: 10.2337/db12-
54. S. E. Kahn, “Incretin Therapy and Islet Pathology: A Time for Caution,” Diabetes, vol. 62, no. 7, pp. 2178–2180, Jul. 2013, doi: 10.2337/db13-0520.
55. F. and D. Administration, “FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes,” 2024, [Online]. Available: http://www.fda.gov/Drugs/DrugSafety/ucm343187.htm
56. B. M. Scirica et al., “Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus,” N. Engl. J. Med., vol. 369, no. 14, pp. 1317–1326, Oct. 2013, doi: 10.1056/NEJMoa1307684.
57. W. B. White et al., “Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes,” N. Engl. J. Med., vol. 369, no. 14, pp. 1327–1335, Oct. 2013, doi: 10.1056/NEJMoa1305889.
58. A. López-Ruiz et al., “Acute renal failure when exenatide is co-administered with diuretics and angiotensin II blockers,” Pharm. World Sci., 2010, doi: 10.1007/s11096-010-9423-8.
59. Y. Kaakeh, S. Kanjee, K. Boone, and J. Sutton, “Liraglutide‐Induced Acute Kidney Injury,” Pharmacother. J. Hum. Pharmacol. Drug Ther., vol. 32, no. 1, Jan. 2012, doi: 10.1002/PHAR.1014.
60. H. Nandakoban, T. J. Furlong, and J. R. Flack, “Acute tubulointerstitial nephritis following treatment with exenatide,” Diabet. Med., vol. 30, no. 1, pp. 123–125, Jan. 2013, doi: 10.1111/j.1464-5491.2012.03738.x.
61. W. J. Weise, M. S. Sivanandy, C. A. Block, and R. J. Comi, “Exenatide-Associated Ischemic Renal Failure,” Diabetes Care, vol. 32, no. 2, pp. e22–e23, Feb. 2009, doi: 10.2337/dc08-1309.
62. B. M. Kuehn, “Exenatide and Kidney Function,” JAMA, vol. 302, no. 24, p. 2644, Dec. 2009, doi: 10.1001/jama.2009.1847.
63. M. E. J. Lean, J. K. Powrie, A. S. Anderson, and P. H. Garthwaite, “Obesity, Weight Loss and Prognosis in Type 2 Diabetes,” Diabet. Med., vol. 7, no. 3, pp. 228–233, Mar. 1990, doi: 10.1111/j.1464-5491.1990.tb01375.x.

64. L. S. Aucott, “Influences of weight loss on long-term diabetes outcomes,” Proc. Nutr. Soc., vol. 67, no. 1, pp. 54–59, Feb. 2008, doi: 10.1017/S0029665108006022.
65. K. Fujioka, “Benefits of moderate weight loss in patients with type 2 diabetes,” Diabetes, Obes. Metab., vol. 12, no. 3, pp. 186–194, Mar. 2010, doi: 10.1111/j.1463-1326.2009.01155.x.
66. J. R. Ussher and D. J. Drucker, “Cardiovascular Biology of the Incretin System,” Endocr. Rev., vol. 33, no. 2, pp. 187–215, Apr. 2012, doi: 10.1210/er.2011-1052.
67. M. Davies, R. Pratley, M. Hammer, A. B. Thomsen, and R. Cuddihy, “Liraglutide improves treatment satisfaction in people with Type 2 diabetes compared with sitagliptin, each as an add on to metformin,” Diabet. Med., vol. 28, no. 3, pp. 333–337, Mar. 2011, doi: 10.1111/j.1464- 5491.2010.03074.x.
68. J. H. Best et al., “Weight-Related Quality of Life, Health Utility, Psychological Well-Being, and Satisfaction With Exenatide Once Weekly Compared With Sitagliptin or Pioglitazone After 26 Weeks of Treatment,” Diabetes Care, vol. 34, no. 2, pp. 314–319, Feb. 2011, doi: 10.2337/dc10- 1119.