![Open Access](https://i-scholar.in/lib/pkp/templates/images/icons/fulltextgreen.png)
![Restricted Access](https://i-scholar.in/lib/pkp/templates/images/icons/fulltextred.png)
The Journey of Vildagliptin: From Bench to Bedside
Subscribe/Renew Journal
Vildagliptin, a DPP-4 inhibitor has been available for the management of type 2 diabetes mellitus for more than a decade. The extensive clinical data support from several vildagliptin clinical trials and real-world studies provided the clinicians with an effective treatment option for lowering blood glucose, which neither causes weight gain nor increased the risk of hypoglycemia and cardiovascular events. This article reviews the development journey of vildagliptin from the proof-of-concept of DPP-4 inhibition from its earlystages in the 1990s to the present, being an extensively studied, well-established DPP-4 inhibitor.The article highlights the clinical effectiveness, safety, and tolerability studies of vildagliptin, which proved vildagliptin as an effective and safe option in the armamentarium of type 2 diabetes mellitus management in this era of evidence-based medical practice. This vildagliptin journey, from proof-of-concept to a very well-established molecule gives a lesson that a novel concept takes time and requires focused efforts, persistence, and long-term perseverance for bringing it into clinical practice.
Keywords
- Ahrén B. DPP-4 inhibition and the path to clinical proof.Front Endocrinol (Lausanne). 2019;10:376.
- Mathieu C, Kozlovski P, Paldánius PM, et al. Clinical safety and tolerability of vildagliptin - insights from randomised trials, observational studies and post-marketing surveillance. Eur Endocrinol. 2017;13(2):68-72.
- Foley JE. Insights Into GLP-1 and GIP Actions Emerging From Vildagliptin Mechanism Studies in Man. Front Endocrinol (Lausanne). 2019;10:780.
- Foley JE, Ahrén B. The vildagliptin experience - 25 years since the initiation of the novartis glucagon-like peptide-1 based therapy programme and 10 years since the first vildagliptin registration. Eur Endocrinol. 2017;13(2):56-61.
- Ahrén B, Simonsson E, Larsson H, et al. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care. 2002;25(5):869875.
- Winzelll M, Ahrén B. The high-fat diet–fed mouse: A model for studying mechanisms and treatment of impaired glucose tolerance and Type 2 Diabetes. Diabetes. 2004;53 Suppl 3:S215-9.
- BAhrén, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of Dipeptidyl Peptidase-4 Reduces Glycemia, Sustains Insulin Levels, and Reduces Glucagon Levels in Type 2 Diabetes. J Clin Endocrinol Metab.2004;89(5):2078-2084.
- Ahrén B, Gomis R, Standl E, Mills D, Schweizer A. Twelveand 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care. 2004;27(12):2874-2880.
- Ahren B, Pacini G, Foley JE, Schweizer A. Improved mealrelated β-Cell functionand insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1year. Diabetes Care.2005;28(8):1936-1940.
- Committee for Medicinal Products for Human Use.European Medicines Agency- CHMP Assessment Report (Vildagliptin). 2012 September; 20.
- Iftekar M, Kalaiselvan V, Gyanendra NS. Efficacy and safety of Vildagliptin in the management of type 2 Diabetes Mellitus. Indian J Pharm Pract. 2012;5(4):8-15.
- Prato SD. Ten years of Vildagliptin. Eur Endocrinol.2017;13(2):54-55.
- Mohan V, Zargar A, Chawla M, et al. Efficacy of a combination of metformin and vildagliptin in comparison to metformin alone in type 2 diabetes mellitus: A multicentre, retrospective, real-world evidence study. Diabetes, Metab Syndr Obes Targets Ther. 2021;14:2925-2933.
- Keating GM. Vildagliptin: a review of its use in Type 2 Diabetes Mellitus. Drugs. 2014;74(5):587-610.
- Garber AJ, Foley JE, Banerji MA, et al. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes, Obes Metab. 2008;10(11):1047-1056.
- Rosenstock J, Baron MA, Camisasca RP, Cressier F, Couturier A, Dejager S. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes.Diabetes, Obes Metab. 2007;9(2):175-185.
- Kikuchi M, Haneda M, Koya D, et al. Efficacy and tolerability of vildagliptin as an add-on to glimepiride in Japanese patients with Type 2 diabetes mellitus. Diabetes Res Clin Pract.2010;89(3):216-223.
- Lukashevich V, Prato SD, Araga M, Kothny W. Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea. Diabetes, Obes Metab. 2014;16(5):403-409.
- Derosa G, Maffioli P, Ferrari I, et al. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride inpoorly controlled type 2 diabetic patients. Horm Metab Res.2010;42(9):663-669.
- Lukashevich V, Schweizer A, Shao Q, Groop PH, Kothny W. Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: A prospective 24-week randomized placebo-controlled trial. Diabetes, Obes Metab. 2011;13(10):947-954.
- Schweizer A, Dejager S, Bosi E. Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: A 24-week, double-blind, randomized trial.Diabetes, Obes Metab. 2009;11(8):804-812.
- Strain WD, Lukashevich V, Kothny W, Hoellinger MJ, Paldánius PM. Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): A 24 week, randomised, doubleblind, placebo-controlled study. Lancet. 2013;382(9890):409-416.
- Mcmurray JJV, Ponikowski P, Bolli GB, et al. effects of vildagliptin on ventricular function in patients with Type 2 Diabetes Mellitus and Heart Failure. A randomized placebo-controlled trial. J Am Coll Cardiol Hear Fail. 2018;6(1):8-17.
- Mathieu C, Barnett AH, Brath H, Conget I, Castro JJ De. Effectiveness and tolerability of second-line therapy with vildagliptin vs . other oral agents in type 2 diabetes : A reallife worldwide observational study (EDGE). Int J Clin Pract. 2013;67(10):947-956.
- Rosales R, Jaoude EA, M Al-Arouj, A Fawwad, A Orabi, P Shah, S DiTommaso, J Vaz ZAL. Clinical effectiveness and safety of vildagliptin in > 19,000 patients with type 2 diabetes : the GUARD study. Diabetes, Obes Metab. 2015;17(6):603- 607.
- Matthias Blüher, Ira Kurz, Simone Dannenmaier MD. Efficacy and safety of vildagliptin in clinical practice-results of the PROVIL-study. World J Diabetes. 2012;3(9):161-169.
- Al-Arouj M, Hassoun AAK, Medlej R, et al. The effect of vildagliptin relative to sulphonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: The VIRTUE study. Int J Clin Pract. 2013;67(10):957-963.
- Halimi S, Levy M, Huet D, Quéré S, Dejager S. Experience with vildagliptin in type 2 diabetic patients fasting during Ramadan in France: Insights from the VERDI study. Diabetes Ther. 2013;4(2):385-398.
- Hassanein M, Hanif W, Malik W, et al. Comparison of the dipeptidyl peptidase-4 inhibitor vildagliptin and the sulphonylurea gliclazide in combination with metformin, in Muslim patients with type 2 diabetes mellitus fasting during Ramadan: Results of the VECTOR study. Curr Med Res Opin. 2011;27(7):1367-1374.
- Shete A, Shaikh A, Nayeem KJ, Lily Rodrigues MSSA, Shah P, Khanna R, Majid S, SA Rasheed, Shehla Shaikh TR. Vildagliptin vs sulfonylurea in Indian Muslim diabetes patients fasting during Ramadan. World J Diabetes. 2013;4(6):358.
- Chawla M, Kim TH, Mirasol RC, Faruque P, Hours-zesiger P, Shete A. Initial combination therapy with vildagliptin plus metformin in drug-naïve patients with T2DM: a 24- week real-life study from Asia. Curr Med Res Opin. 2018;34(9):1605-1611.
- Matthews DR, Paldánius PM, Proot P, Chiang Y, Stumvoll M, Prato SD. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year , multicentre , randomised, doubleblind trial. Lancet. 2019;394(10208):1519-1529.
- Matthews D, Del S, Viswanathan P, Mathieu C, Vencio S, Chan JCN. Insights from VERIFY: Early combination therapy provides better glycaemic durability than a stepwise approach in newly diagnosed Type 2 Diabetes. Diabetes Ther. 2020;11(11):2465-2476.
![](https://i-scholar.in/public/site/images/abstractview.png)
Abstract Views: 170
![](https://i-scholar.in/public/site/images/pdfview.png)
PDF Views: 96