Research Article| Volume 157, 107860, November 2019

Efficacy and safety of evogliptin versus sitagliptin as an add-on therapy in Indian patients with type 2 diabetes mellitus inadequately controlled with metformin: A 24-week randomized, double-blind, non-inferiority, EVOLUTION INDIA study

Published:September 14, 2019DOI:



      This study aimed to assess efficacy and safety of evogliptin versus sitagliptin, when added to background metformin therapy in Indian patients with uncontrolled type 2 diabetes.


      Overall, 184 patients with uncontrolled type 2 diabetes (7% ≤ HbA1c < 10%) receiving ≥8 weeks of stable metformin monotherapy (≥1 g/day), were randomized to receive add-on treatment (evogliptin 5 mg or sitagliptin 100 mg) for 24 weeks. Primary endpoint was change in HbA1c from baseline to 12 weeks (non-inferiority margin: <0.35).


      Mean reductions in HbA1c at 12 weeks in evogliptin- and sitagliptin-treated patients were −0.37 (1.06) and –0.32 (1.14), respectively. The adjusted mean difference between treatment groups was –0.022 (95% CI: –0.374, 0.330; P = 0.901), that demonstrated non-inferiority. Reductions in FPG and PPG were similar between evogliptin and sitagliptin at 12 and 24 weeks. Changes in body weight were comparable between the treatment groups. Patients achieving target HbA1c < 7.0% (evogliptin, 26.7% vs. sitagliptin, 20%) was almost equal in both groups. Treatment-emergent adverse events occured in 52 patients (evogliptin, 25% and sitagliptin, 31.5%) and were generally mild.


      Evogliptin was non-inferior to sitagliptin in HbA1c reduction. It effectively improved glycemic control and was well tolerated in type 2 diabetes patients inadequately controlled by metformin alone.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Diabetes Research and Clinical Practice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • International Diabetes Federation
        IDF Diabetes Atlas.
        International Diabetes Federation, Brussels, Belgium2017 ([Accessed 22 October 2018])
        • Tandon N.
        • Anjana R.M.
        • Mohan V.
        • et al.
        India State-Level Disease Burden Initiative Diabetes Collaborators. The increasing burden of diabetes and variations among the states of India: the global burden of disease study 1990–2016.
        Lancet Glob Health. 2018; 6: e1352-e1362
        • Bajaj S
        RSSDI clinical practice recommendations for the management of type 2 diabetes mellitus 2017.
        Int J Diabetes Dev Ctries. 2018; 38: 1-115
        • American Diabetes Association
        Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018.
        Diabetes Care. 2018; 41: S73-S85
      1. International Diabetes Federation. Recommendations for managing type 2 diabetes in primary care, 2017. [Accessed 23 October 2018].

        • Garber A.J.
        • Garber A.J.
        • Abrahamson M.J.
        • et al.
        Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm–2016 executive summary.
        Endocr Pract. 2016; 22: 84-113
        • Nauck M.A.
        Unraveling the science of incretin biology.
        Am J Med. 2009; 122: S3-S10
        • Scirica B.M.
        • Bhatt D.L.
        • Braunwald E.
        • et al.
        SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.
        N Engl J Med. 2013; 369: 1317-1326
        • Green J.B.
        • Bethel M.A.
        • Armstrong P.W.
        • et al.
        Effect of Sitagliptin on cardiovascular outcomes in type 2 diabetes.
        N Engl J Med. 2015; 373: 232-242
        • White W.B.
        • Cannon C.P.
        • Heller S.R.
        • et al.
        Alogliptin after acute coronary syndrome in patients with type 2 diabetes.
        N Engl J Med. 2013; 369: 1327-1335
        • Gu N.
        • Park M.K.
        • Kim T.E.
        • et al.
        Multiple-dose pharmacokinetics and pharmacodynamics of evogliptin (DA-1229), a novel dipeptidyl peptidase IV inhibitor, in healthy volunteers.
        Drug Des Devel Ther. 2014; 8: 1709-1721
        • Jung C.H.
        • Park C.Y.
        • Ahn K.J.
        • et al.
        A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise.
        Diabetes Metab Res Rev. 2015; 31: 295-306
        • Park J.
        • Park S.W.
        • Yoon K.H.
        • et al.
        Efficacy and safety of evogliptin monotherapy in patients with type 2 diabetes and moderately elevated glycated haemoglobin levels after diet and exercise.
        Diabetes Obes Metab. 2017; 19: 1681-1687
        • Oh J
        • Kim A.H.J.
        • Lee S.H.
        • et al.
        Effects of renal impairment on the pharmacokinetics and pharmacodynamics of a novel dipeptidyl peptidase-4 inhibitor, evogliptin (DA-1229).
        Diabetes Obes Metab. 2017; 19: 294-298
        • Hong SM
        • Park C.Y.
        • Hwang D.M.
        • et al.
        Efficacy and safety of adding evogliptin versus sitagliptin for metformin-treated patients with type 2 diabetes: A 24-week randomized, controlled trial with open label extension.
        Diabetes Obes Metab. 2017; 19: 654-663
        • Hanefeld M.
        • Herman G.A.
        • Wu M.
        • et al.
        Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes.
        Curr Med Res Opin. 2007; 23: 1329-1339
        • Ristic S.
        • Byiers S.
        • Foley J.
        • et al.
        Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response.
        Diabetes Obes Metab. 2005; 7: 692-698
        • Scheen A.J.
        • Charpentier G.
        • Ostgren C.J.
        • et al.
        Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus.
        Diabetes Metab Res Rev. 2010; 26: 540-549
        • Alanazi A.S.
        Systematic review and meta-analysis of efficacy and safety of combinational therapy with metformin and dipeptidyl peptidase-4 inhibitors.
        Saudi Pharm J. 2015; 23: 603-613