Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

  • Naghma Ms.
  • Sadia M Azam Khan
  • Atta Ullah Khan
  • Zahoor Ahmed
  • Muhammad Umar
  • Muhammad Shabbir Khan
Keywords: Anti-diabetic, HbA1C, Sulfonylurea, DPP–4 Inhibitors, NMC, KMC


Objective: This trial was conducted to evaluate the effectiveness of oral hypoglycemic agents on diabetic control and biochemical parameters of known diabetic subjects.

Introduction:  T2DM   occurs due to abnormal metabolism of carbohydrate, proteins and lipids leading to increased blood glucose characterized by polyuria and polydypsia due to relative 5deficiency or lack of insulin. Beside dietary control and insulin therapy, various oral hypoglycemic such as sulfonylurea biguanide, thiazolidinedione, DPP–4 inhibitors, glucagon–like peptide inhibitors and SGL2.


Material and Methods: This comparative trial was carried out on previously diagnosed type–2 diabetic subjects. This trial was conducted at health care centers of District Nowshehra viz. NMC Nowshehra, DHQ Hospital Nowshehra, and ICS, Peshawar in collaboration with KMC and PIMC Peshawar, Khyber Pakhtunkhwa, Pakistan. A total of 200 known diabetic subjects were randomly recruited on the basis of predetermined selection criteria and were splited into two groups. Group A having 100 diabetic subjects was given DPP4 inhibitor; Sitagliptin 50 mg two times a day alone for six (06) months while Group B comprising of 100 patients were treated   with combination of DPP–4 inhibitor (Sitagliptin 50 mg 1BD) and Metformin in a dose of 500 mg two times a day. Venous blood samples were taken from each patient in both fasting (10–12 hour night long fast) and random (2 hour post prandial) state. FBS, RBS, HbA1C, S. creatinine and fasting S. lipid profile were determined by using spectrophotometric colorimetric methods using kits (procured from Elitech, Spain) at  03 and 06 months follow up. Inclusion criteria was subjects with T2DM of age 18 years and above. T2DM patients on insulin, diabetic nephropathy and retinopathy were excluded. The data was analyzed by using SPSS software version 20.

Results: Significant results (p < 0.05) were seen for glycemic control (FBS, RBS, HbA1C) in Group B as compare to Group A patients.


1. Word Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation on Obesity. Geneva, 3-5 June 1997.
2. Rehman, A. Khan, S. A.; Hamayun, M. Studies on diabetic neuropathy and secondary disease in Type 2 Diabetes. Int. J. Diab. 2005; 25:111–112.
3. 2. Skyler, J. S. Bakris, G. L. Bonifacio, E. Darsow, T. Eckel, R. H. Groop, L. Differentiation of diabetes by pathophysiology, natural history and diagnosis. Diabetes. 2017; 66:241–255.
4. 3. Saxena, R. Hiver, M. F. Langenberg, C. Tanaka, T. Pankow, J. S. Vollenweider, P. et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010; 42:142–148.
5. Nauck, M. A. Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med. 2011; 124:S3–S18.
6. Inzucchi, S. E. Bergenstal, R. M. Buse, J. B. Diamant, M, Ferrannini, E. Nauck, M. Peters, A. L. Tsapas, A. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes. Diabetologia. 2012; 55:1577–1596.
7. Wang, T. J. Larson, M. G. Vasan, R. S. Cheng, S. Rhee, E. P. Cabe, E. et al., Metabolite profiles and the risk of developing diabetes. Nat Med. 2011; 17:448–453.
8. Cowie, C. C. Rust, K. F, Byrd, D. D. Gregg, E. W. Ford, E. S. Geiss, L. S. Prevalence of diabetes and high risk for diabetes using A1C criteria in the US population in 1988-2006. Diabetes Care. 2010; 33:562–568.
9. Saran, R.; Robinson, B. Abbott, K. C. Vahakn, S. John, A. Nickol. B et al. US Renal Data System 2019 Annual Data Report: epidemiology of kidney disease in the United States. Am J Kidney Dis. 2020; 75:S1–S64.
10. Monami, M. Dicembrini, I. Antenore, A. Mannucci, E. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care. 2011; 34:2474–2476.
11. Erin, E. Mulvihill, Daniel, J, Drucke. Pharmacology, Physiology, and Mechanisms of Action of Dipeptidyl Peptidase–4 Inhibitors. Endocrine Reviews. 2014; 35:992–1019.
12. Lu, G. Hu, Y. Wang, Q. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature. 2013; 500:227–231.
13. Davidson, J. A. The placement of DPP-4 inhibitors in clinical practice recommendations for the treatment of type 2 diabetes. Endocr Pract. 2013; 19:1050–1061.
14. Deacon CF, Holst J J. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother. 2013: 14:2047–2058.
15. Ussher, J. R. Drucker, D. J. Cardiovascular biology of the incretin system. Endocr Rev. 2012; 33:187–215.
16. Solun, B. Marcoviciu, D. Dicker, D. Dipeptidyl peptidase-4 inhibitors and their effects on the cardiovascular system. Curr Cardio Rep. 2013; 15:382–187.
17. Puepet FH, Zoakah AI, Chuhwak EK. Prevalence of overweight and obesity among urban Nigeria adults in Jos. Highland Med Res J. 2002; 1(1):13−6.
18. Puoane T, Fourie JM, Shapiro M, Rosling L, Tshaka NC, Oelefse A. ‘Big is beautiful’ – an exploration with urban black community health workers in a South African township. South African J Clin Nutr. 2005; 18(1):8−15.
19. Hanson RL, Imperatore G, Bennett PH, Knowler WC. Components of the “metabolic syndrome” and incidence of type 2 diabetes. Diabetes 2002;51(10):3120−7.
20. Baker JL, Olsen LW, Sorvusen TI. Childhood body mass index and the risk of coronary heart disease in adulthood. N Eng J Med. 2007; 357(23):2329−37.
21. Abbas S, Shazia A, Riaz A, Malik N. Risk factors for coronary artery disease in Pakistan. Pak Armed Forces Med J 2003; 53:12–9.
22. Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldslien DE, Little RR, et al. Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in US adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care. 1988; 21:518–24.
23. Scheen, A. J. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes. Postgrad Med. 2013; 125:7–20.
24. Ramirez, G. Morrison, A. D. Bittle, P. A. Clinical practice considerations and review of the literature for the use of DPP–4 inhibitors in patients with type 2 diabetes and chronic kidney disease. Endocr Pract. 2013; 1025–1034.
25. Drucker DJ, Yusta B. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annu Rev Physiol. 2014; 76:561–583.
26. Mentlein, R.; Gallwitz, B.; Schmidt, W. E. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1 amide, peptide histidine methionine and is responsible for their degradatition in human serum. Eur J Biochem. 1993; 214:829–835.
27. Egan, A. G. Blind, E. Dunder, K.; et al. Pancreatic safety of incretin-based drugs–FDA and EMA assessment. N. Engl. J. Med. 2014; 370:794–797.
28. Ahren, B. Simonsson, E. Larsson, H. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4–week study period in type 2 diabetes. Diabetes Care. 2002; 25:869–875.
29. Nakamura, K. Oe, H. Kihara, H. DPP-4 inhibitor and glucosidase inhibitor equally improve endothelial function in patients with type 2diabetes: EDGE study. Cardiovasc Diabetol. 2014; 13:110.
30. Alsalim, W. Goransson, O. Tura, A. Pacini, G. Mari, A. Ahren. B. Persistent whole day meal effects of three dipeptidyl peptidase-4 inhibitors on glycaemia and hormonal responses in metformin-treated type 2 diabetes. Diabetes Obes Metab. 2020; 22:590–598.
31. Chehregosha, H. Khamseh, M. E. Malek, M. Hosseinpanah, F. Ismail B. F. A view beyond HbA1c: role of continuous glucose monitoring. Diabetes Ther. 2019; 10:853–863.
32. Sharma, M. Beckley, N. Nazareth, I. Peterson, I. Effectiveness of sitagliptin compared to sulfonylureas for type 2 diabetes mellitus inadequately controlled on metformin: a systematic review and meta-analysis. BMJ Open. 2017; 7:017260.
33. Jain. R. Utility of Saxagliptin in the Treatment of Type 2 Diabetes: Review of Efficacy and Safety. Adv Ther. 2015; 32:1065–1084.
34. Amir, Q. MichaeL, J.B. Linda, L. Humphrey, and Mary A. F. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline Update from the American College of Physicians. Ann Intern Med. 2017; 166:279–290.
35. Sangmo, H. Kyungdo, H. and Cheol, Y. P. Outcomes for Inappropriate Renal Dose
Adjustment of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes
Mellitus: Population-Based Study. Mayo Clin Proc. 2020; 95:101–112.
36. Zhenhua, L. Lanting, X. Meimei, X. Xiaojie, X. Jinfeng, W. Jinmei, W. Wenyi, Kang. Trelagliptin succinate: DPP–4 inhibitor to improve insulin resistance in adipocytes. Biomedicine and Pharmacotherapy. 2020; 125:109952.
37. Avogaro, A. Delgado, E. Lingvay, I. When metformin is not enough: pros and cons of SGLT2 and DPP-4 inhibitors as a second line therapy. Diabetes Metab Res Rev. 2018; 34:2981–2986.
How to Cite
Ms. N, Khan S, Khan A, Ahmed Z, Umar M, Khan M. Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial. JRMC [Internet]. 30Dec.2020 [cited 23Jan.2021];24(4):368-73. Available from: http://journalrmc.com/index.php/JRMC/article/view/1462

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