Once daily versus twice daily Linagliptin effect on glycemic levels in type 2 diabetes mellitus- an observational study

Riyaz Mohammed, Mohammed Azfar Ali


Background: DPP-4 is widely distributed in endothelial cells, pancreas, uterus, liver, salivary glands, lymph node, spleen, and thymus. DPP-4 regulates glucagon-like peptide (GLP)-1, and glucose-dependent insulin tropic peptide (GIP) which leads to glucose homeostasis via enhancing insulin secretion and suppression of glucagon, which results in control of post-prandial and fasting hyperglycemia.

Methods: These 40 patients who were enrolled as per the inclusion criteria of receiving metformin dosage of 2 gram per day in established type 2 diabetes mellitus patients with no comorbidities. these patients were divided randomly into two groups comprising of 20 patients each, group A received linagliptin 5 mg per day in addition to metformin 1gm twice daily whereas group B received linagliptin 5 mg per day in a fixed dose (Linagliptin + metformin) of 2.5/1000 twice daily.

Results: In the present observational study, the mean age in group A was 46.7±9.4 compared to 51.65±9.9 in group B, p >0.05, mean BMI in group A was 27.8±1.1 compared to 27.28±0.93 in group B p >0.05, Mean FBS in group A was 157.9±24.1 compared to 146.2±21.8 in group B p >0.05, Mean PPBS in group A was 245.8±32.7 compared to 246.2±39.3 in group B p >0.05 and Mean HbA1c in group A was 7.67±0.58 compared to 7.6±0.5 in group B p >0.05. Group A patients were initiated on once daily linagliptin, there was a significant reduction in FBS, PPBS and HbA1c at the end of 6 months p <0.001. Similarly, Group B patients who were initiated on twice daily linagliptin also showed a significant reduction in FBS, PPBS and HbA1c at the end of 6 months p <0.001.

Conclusions: The addition of linagliptin to metformin treatment was effective and well tolerated in patients with type 2 diabetes. Linagliptin add-on to metformin during the early course of treatment helps in delaying the exhaustion of pancreatic islet function. Plasma concentrations of linagliptin decline in at least a biphasic manner with a long terminal half-life (>100 hours), related to the saturable binding of linagliptin to DPP-4. The prolonged elimination phase does not contribute to the accumulation of the drug. Addition of linagliptin to metformin has shown a significant reduction in FBS, PPBS and HbA1c.


DDP-4, Glycemic levels, Glycosylated haemoglobin, Linagliptin, Metformin, Type 2 diabetes mellitus

Full Text:



Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors. Drugs. 2011;71:1441-67.

Nabeno M, Akahoshi F, Kishida H, Miyaguchi I,Tanaka Y, Ishii S, et al. A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site. Biochemical Biophysical Res Com. 2013;434:191-6.

Scarpello JH, Howlett HC. Metformin therapy and clinical uses. DiabVasc Dis Res. 2008;5:157-67.

Haak T, Meinicke T, Jones R, Weber S, Eynatten MV, Woerle HJ. Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study. J Pharmacol. 2012;14(6):565-74.

Chen Y, Ning G, Wang C, Gong Y, Patel S, Zhang C, et al. Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: a multinational, 24-week, randomized, clinical trial. J Diabetes Investig. 2015;6:692-8.

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-26.

White W. Results from EXAMINE. Oral presentation at EASD 2013. Available at: resources/7109.

Rosenstock J, Marx N, Kahn SE, Zinman B, Kastelein JJ, Lachin JM, et al. Cardiovascular outcome trials in type 2 diabetes and the Sulphonylurea controversy: rationale for the active-comparator CAROLINA trial. Diab Vasc Dis Res. 2013;10:289-301.

Inagaki N, Watada H, Murai M, Kagimura T, Gong Y, Patel S, et al. Linagliptin provides effective, well-tolerated add-on therapy to pre-existing oral antidiabetic therapy over 1 year in Japanese patients with type 2 diabetes. Diabetes Obes Metab. 2013;15:833-43.

Zeng Z, Choi DS, Mohan V, Emser A, Siddiqui K, Gong Y, et al. Linagliptin is efficacious and well tolerated in Asian patients with inadequately controlled type 2 diabetes. Diabetes. 201261(1):A300.