Diabetes

Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus

1.Deacon, C. F. et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 44, 1126–1131 (1995).CAS 
PubMed 

Google Scholar 
2.Davies, M. J. et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 61, 2461–2498 (2018).PubMed 

Google Scholar 
3.Handelsman, Y. et al. American Association of Clinical Endocrinologists and American College of Endocrinology: clinical practice guidelines for developing a diabetes mellitus comprehensive care plan — 2015. Endocr. Pract. 21 (Suppl 1), 1–87 (2015).PubMed 
PubMed Central 

Google Scholar 
4.Garber, A. 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. 22, 84–113 (2016).PubMed 

Google Scholar 
5.Holst, J. J. & Deacon, C. F. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes 47, 663–1670 (1998).
Google Scholar 
6.Kreymann, B., Williams, G., Ghatei, M. A. & Bloom, S. R. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet 2, 1300–1304 (1987).CAS 
PubMed 

Google Scholar 
7.Baggio, L. L. & Drucker, D. J. Biology of incretins: GLP-1 and GIP. Gastroenterology 132, 2131–2157 (2007).CAS 
PubMed 

Google Scholar 
8.Nauck, M. A. et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 741–744 (1993).CAS 
PubMed 

Google Scholar 
9.Amiel, S. A. Glucagon-like peptide: a therapeutic glimmer. Lancet 343, 4–5 (1994).CAS 
PubMed 

Google Scholar 
10.Mentlein, R., Gallwitz, B. & Schmidt, W. E. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur. J. Biochem. 214, 829–835 (1993).CAS 
PubMed 

Google Scholar 
11.Kieffer, T. J., McIntosh, C. H. & Pederson, R. A. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 136, 3585–3596 (1995).CAS 
PubMed 

Google Scholar 
12.Deacon, C. F., Johnsen, A. H. & Holst, J. J. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J. Clin. Endocrinol. Metab. 80, 952–957 (1995).CAS 
PubMed 

Google Scholar 
13.Deacon, C. F., Hughes, T. E. & Holst, J. J. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes 47, 764–769 (1998).CAS 
PubMed 

Google Scholar 
14.Pederson, R. A. et al. Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide. Diabetes 47, 1253–1258 (1998).CAS 
PubMed 

Google Scholar 
15.Ahrén, B. et al. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care 25, 869–875 (2002).PubMed 

Google Scholar 
16.Ahrén, B., Gomis, R., Standl, E., Mills, D. & Schweizer, A. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 27, 2874–2880 (2004).PubMed 

Google Scholar 
17.Esposito, K. et al. Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Obes. Metab. 13, 594–603 (2011).CAS 
PubMed 

Google Scholar 
18.Scheen, A. J. The safety of gliptins: updated data in 2018. Expert Opin. Drug Saf. 17, 387–405 (2018).CAS 
PubMed 

Google Scholar 
19.Deacon, C. F. Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes. Peptides 100, 150–157 (2018).CAS 
PubMed 

Google Scholar 
20.Mulvihill, E. E. & Drucker, D. J. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr. Rev. 35, 992–1019 (2014).CAS 
PubMed 
PubMed Central 

Google Scholar 
21.Mari, A. et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 90, 4888–4894 (2005).CAS 
PubMed 

Google Scholar 
22.Herman, G. A. et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 91, 4612–4619 (2006).CAS 
PubMed 

Google Scholar 
23.Aulinger, B. A. et al. Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes 63, 1079–1092 (2014).CAS 
PubMed 

Google Scholar 
24.Nauck, M. A. et al. Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and patients with type 2 diabetes using exendin [9–39] as a GLP-1 receptor antagonist. Diabetes 65, 2440–2447 (2016).CAS 
PubMed 

Google Scholar 
25.Nauck, M. A. et al. Preserved incretin activity of glucagon-like peptide 1 [7–36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J. Clin. Invest. 91, 301–307 (1993).CAS 
PubMed 
PubMed Central 

Google Scholar 
26.Højberg, P. V. et al. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 52, 199–207 (2009).PubMed 

Google Scholar 
27.Aaboe, K. et al. Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors. Diabetes Obes. Metab. 17, 74–81 (2015).CAS 
PubMed 

Google Scholar 
28.Gasbjerg, L. S. et al. GIP(3-30)NH2 is an efficacious GIP receptor antagonist in humans: a randomised, double-blinded, placebo-controlled, crossover study. Diabetologia 61, 413–423 (2018).CAS 
PubMed 

Google Scholar 
29.Christensen, M., Vedtofte, L., Holst, J. J., Vilsbøll, T. & Knop, F. K. Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes 60, 3103–3109 (2011).CAS 
PubMed 
PubMed Central 

Google Scholar 
30.Christensen, M. B., Calanna, S., Holst, J. J., Vilsbøll, T. & Knop, F. K. Glucose-dependent insulinotropic polypeptide: blood glucose stabilizing effects in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 29, E418–E426 (2014).
Google Scholar 
31.Ahrén, B. et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 9, 1236–1243 (2009).
Google Scholar 
32.Farngren, J., Persson, M., Schweizer, A., Foley, J. E. & Ahrén, B. Glucagon dynamics during hypoglycaemia and food-re-challenge following treatment with vildagliptin in insulin-treated patients with type 2 diabetes. Diabetes Obes. Metab. 16, 812–828 (2014).CAS 
PubMed 

Google Scholar 
33.Mentlein, R. Dipeptidyl-peptidase IV (CD26) — role in the inactivation of regulatory peptides. Regul. Pept. 85, 9–24 (1999).CAS 
PubMed 

Google Scholar 
34.Hopsu-Havu, V. K. & Glenner, G. G. A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide. Histochemie 7, 197–201 (1966).CAS 
PubMed 

Google Scholar 
35.Mentlein, R. Proline residues in the maturation and degradation of peptide hormones and neuropeptides. FEBS Lett. 234, 251–256 (1988).CAS 
PubMed 

Google Scholar 
36.Schön, E. et al. Dipeptidyl peptidase IV in the immune system. Effects of specific enzyme inhibitors on activity of dipeptidyl peptidase IV and proliferation of human lymphocytes. Biol. Chem. Hoppe. Seyler. 372, 305–311 (1991).PubMed 

Google Scholar 
37.Villhauer, E. B. et al. 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J. Med. Chem. 46, 2774–2789 (2003).CAS 
PubMed 

Google Scholar 
38.Augeri, D. J. et al. Discovery and preclinical profile of saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem. 48, 5025–5037 (2005).CAS 
PubMed 

Google Scholar 
39.Rasmussen, H. B., Branner, S., Wiberg, F. C. & Wagtmann, N. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog. Nat. Struct. Biol. 10, 19–25 (2003).CAS 
PubMed 

Google Scholar 
40.Kim, D. et al. 2 R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem. 48, 141–151 (2005).CAS 
PubMed 

Google Scholar 
41.Feng, J. et al. Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV. J. Med. Chem. 50, 2297–2300 (2007).CAS 
PubMed 

Google Scholar 
42.Eckhardt, M. et al. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J. Med. Chem. 50, 6450–6453 (2007).CAS 
PubMed 

Google Scholar 
43.Deacon, C. F. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes. Metab. 13, 7–18 (2011).CAS 
PubMed 

Google Scholar 
44.Herman, G. A. et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin. Pharmacol. Ther. 78, 675–688 (2005).CAS 
PubMed 

Google Scholar 
45.European Medicines Agency. Sitagliptin: summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/januvia-epar-product-information_en.pdf (accessed August 2020).46.Bergman., A. J. et al. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care. 30, 1862–1864 (2007).CAS 
PubMed 

Google Scholar 
47.He, Y. L. Clinical pharmacokinetics and pharmacodynamics of vildagliptin. Clin. Pharmacokinet. 51, 147–162 (2012).CAS 
PubMed 

Google Scholar 
48.European Medicines Agency. Vildagliptin: summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/galvus-epar-product-information_en.pdf (accessed August 2020).49.Boulton, D. W. Clinical pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor. Clin. Pharmacokinet. 56, 11–24 (2017).CAS 
PubMed 

Google Scholar 
50.Boulton, D. W. et al. Influence of renal or hepatic impairment on the pharmacokinetics of saxagliptin. Clin. Pharmacokinet. 50, 253–265 (2011).CAS 
PubMed 

Google Scholar 
51.European Medicines Agency. Saxagliptin: summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/onglyza-epar-product-information_en.pdf (accessed August 2020).52.White, J. R. Alogliptin for the treatment of type 2 diabetes. Drugs Today 47, 99–107 (2011).CAS 
PubMed 

Google Scholar 
53.European Medicines Agency. Alogliptin: summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/vipidia-epar-product-information_en.pdf (accessed August 2020).54.Graefe-Mody, U., Retlich, S. & Friedrich, C. Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin. Pharmacokinet. 51, 411–427 (2012).CAS 
PubMed 

Google Scholar 
55.Graefe-Mody, U. et al. Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin. Diabetes Obes. Metab. 13, 939–946 (2011).CAS 
PubMed 

Google Scholar 
56.European Medicines Agency. Linagliptin: summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/trajenta-epar-product-information_en.pdf (accessed August 2020).57.Graefe-Mody, U. et al. Pharmacokinetics of linagliptin in subjects with hepatic impairment. Br. J. Clin. Pharmacol. 74, 75–85 (2012).CAS 
PubMed 
PubMed Central 

Google Scholar 
58.Ahrén, B. et al. Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans. Diabetes Obes. Metab. 13, 775–783 (2011).PubMed 

Google Scholar 
59.Nabeno, M. et al. A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site. Biochem. Biophys. Res. Commun. 434, 191–196 (2013).CAS 
PubMed 

Google Scholar 
60.Tatosian, D. A. et al. Dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes treated with saxagliptin, sitagliptin, or vildagliptin. Diabetes Ther. 4, 431–442 (2013).PubMed 
PubMed Central 

Google Scholar 
61.Baranov, O., Kahle, M., Deacon, C. F., Holst, J. J. & Nauck, M. A. Feedback suppression of meal-induced glucagon-like peptide-1 (GLP-1) secretion mediated through elevations in intact GLP-1 caused by dipeptidyl peptidase-4 inhibition: a randomized, prospective comparison of sitagliptin and vildagliptin treatment. Diabetes Obes. Metab. 18, 1100–1109 (2016).CAS 
PubMed 

Google Scholar 
62.Alsalim, W. et al. 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. 22, 590–598 (2020).CAS 
PubMed 

Google Scholar 
63.Scheen, A. J., Charpentier, G., Ostgren, C. J., Hellqvist, A. & Gause-Nilsson, I. 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. 26, 540–549 (2010).CAS 
PubMed 

Google Scholar 
64.Rizzo, M. R., Barbieri, M., Marfella, R. & Paolisso, G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 35, 2076–2082 (2012).CAS 
PubMed 
PubMed Central 

Google Scholar 
65.Kothny, W., Lukashevich, V., Foley, J. E., Rendell, M. S. & Schweizer, A. Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial. Diabetologia 58, 2020–2026 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
66.Deacon, C. F. & Lebovitz, H. E. Comparative review of dipeptidyl peptidase-4 inhibitors and sulphonylureas. Diabetes Obes. Metab. 18, 333–347 (2016).CAS 
PubMed 

Google Scholar 
67.Inagaki, N., Onouchi, H., Maezawa, H., Kuroda, S. & Kaku, K. Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2 diabetes: a randomised, double-blind, phase 3, non-inferiority study. Lancet Diabetes Endocrinol. 3, 191–197 (2015).CAS 
PubMed 

Google Scholar 
68.Addy, C. et al. Pharmacokinetic and pharmacodynamic effects of multiple-dose administration of omarigliptin, a once-weekly dipeptidyl peptidase-4 inhibitor, in obese participants with and without type 2 diabetes mellitus. Clin. Ther. 38, 516–530 (2016).CAS 
PubMed 

Google Scholar 
69.Goldenberg, R. et al. Randomized clinical trial comparing the efficacy and safety of treatment with the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or the once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Diabetes Obes. Metab. 19, 394–400 (2017).CAS 
PubMed 
PubMed Central 

Google Scholar 
70.Kim, Y. G. et al. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia 56, 696–708 (2013).CAS 
PubMed 

Google Scholar 
71.Cai, X., Han, X., Luo, Y. & Ji, L. Efficacy of dipeptidyl-peptidase-4 inhibitors and impact on β-cell function in Asian and Caucasian type 2 diabetes mellitus patients: a meta-analysis. J. Diabetes 7, 347–359 (2015).CAS 
PubMed 

Google Scholar 
72.Gao, W., Wang, Q. & Yu, S. Efficacy, safety and impact on β-cell function of dipeptidyl peptidase-4 inhibitors plus metformin combination therapy in patients with type 2 diabetes and the difference between Asians and Caucasians: a meta-analysis. J. Endocrinol. Invest. 39, 1061–1074 (2016).CAS 
PubMed 

Google Scholar 
73.Kozlovski, P. et al. Effect of race and ethnicity on vildagliptin efficacy: a pooled analysis of phase II and III studies. Diabetes Obes. Metab. 19, 429–435 (2017).CAS 
PubMed 
PubMed Central 

Google Scholar 
74.Morimoto, C. & Schlossman, S. F. The structure and function of CD26 in the T-cell immune response. Immunol. Rev. 161, 55–70 (1998).CAS 
PubMed 

Google Scholar 
75.Ohnuma, K., Dang, N. H. & Morimoto, C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends. Immunol. 29, 295–301 (2008).CAS 
PubMed 

Google Scholar 
76.Hühn, J., Ehrlich, S., Fleischer, B. & von Bonin, A. Molecular analysis of CD26 mediated signal transduction in T cells. Immunol. Lett. 72, 127–32 (2000).PubMed 

Google Scholar 
77.Anz, D. et al. The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses. Diabetes Obes. Metab. 16, 569–572 (2014).CAS 
PubMed 

Google Scholar 
78.Goodwin, S. R. et al. Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study. J. Clin. Endocrinol. Metab. 98, 743–745 (2013).CAS 
PubMed 

Google Scholar 
79.Dubé, M. P. et al. A randomized, double-blinded, placebo-controlled trial of sitagliptin for reducing inflammation and immune activation in treated and suppressed human immunodeficiency virus infection. Clin. Infect. Dis. 69, 1165–1172 (2019).PubMed 

Google Scholar 
80.Pratley, R. E., McCall, T., Fleck, P. R., Wilson, C. A. & Mekki, Q. Alogliptin use in elderly people: a pooled analysis from phase 2 and 3 studies. J. Am. Geriatr. Soc. 57, 2011–2019 (2009).PubMed 

Google Scholar 
81.Lehrke, M. et al. Safety and tolerability of linagliptin in patients with type 2 diabetes: a comprehensive pooled analysis of 22 placebo-controlled studies. Clin. Ther. 36, 1130–1146 (2014).CAS 
PubMed 

Google Scholar 
82.Hirshberg, B., Parker, A., Edelberg, H., Donovan, M. & Iqbal, N. Safety of saxagliptin: events of special interest in 9156 patients with type 2 diabetes mellitus. Diabetes Metab. Res. Rev. 30, 556–569 (2014).CAS 
PubMed 

Google Scholar 
83.Engel, S. S., Round, E., Golm, G. T., Kaufman, K. D. & Goldstein, B. J. Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies. Diabetes Ther. 4, 119–145 (2013).PubMed 
PubMed Central 

Google Scholar 
84.Schweizer, A., Dejager, S., Foley, J. E. & Kothny, W. Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies. Vasc. Health Risk Manag. 7, 49–57 (2011).PubMed 
PubMed Central 

Google Scholar 
85.Scirica, B. M. et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N. Engl. J. Med. 369, 1317–1326 (2013).CAS 
PubMed 

Google Scholar 
86.White, W. B. et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369, 1327–1335 (2013).CAS 
PubMed 

Google Scholar 
87.Green, J. B. et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373, 232–242 (2015).CAS 
PubMed 

Google Scholar 
88.Rosenstock, J. et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA 321, 69–79 (2019).CAS 
PubMed 

Google Scholar 
89.Rosenstock, J. et al. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. JAMA 322, 1155–1166 (2019).CAS 
PubMed Central 

Google Scholar 
90.Aaboe, K. et al. Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and non-glucose induced insulin secretion in patients with type 2 diabetes mellitus. Diabetes Obes. Metab. 12, 323–333 (2010).CAS 
PubMed 

Google Scholar 
91.Butler, P. C., Elashoff, M., Elashoff, R. & Gale, E. A. A critical analysis of the clinical use of incretin-based therapies: are the GLP-1 therapies safe? Diabetes Care. 36, 2118–2125 (2013).PubMed 
PubMed Central 

Google Scholar 
92.Nauck, M. A. A critical analysis of the clinical use of incretin-based therapies: the benefits by far outweigh the potential risks. Diabetes Care. 36, 2126–2232 (2013).PubMed 
PubMed Central 

Google Scholar 
93.Egan, A. G. et al. Pancreatic safety of incretin-based drugs — FDA and EMA assessment. N. Engl. J. Med. 370, 794–797 (2014).CAS 
PubMed 

Google Scholar 
94.Meier, J. J. & Nauck, M. A. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia 57, 1320–1324 (2014).CAS 
PubMed 

Google Scholar 
95.Abd El Aziz, M., Cahyadi, O., Meier, J. J., Schmidt, W. E. & Nauck, M. A. Incretin-based glucose-lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based on cardiovascular outcomes trials. Diabetes Obes. Metab. 22, 699–704 (2020).CAS 
PubMed 

Google Scholar 
96.Azoulay, L. et al. Association between incretin-based drugs and the risk of acute pancreatitis. JAMA Intern. Med. 176, 1464–1473 (2016).PubMed 

Google Scholar 
97.Lai, Y. J., Hu, H. Y., Chen, H. H. & Chou, P. Dipeptidyl peptidase-4 inhibitors and the risk of acute pancreatitis in patients with type 2 diabetes in Taiwan: a population-based cohort study. Medicine 94, e1906 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
98.Dicembrini, I., Montereggi, C., Nreu, B., Mannucci, E. & Monami, M. Pancreatitis and pancreatic cancer in patients treated with dipeptidyl peptidase-4 inhibitors: an extensive and updated meta-analysis of randomized controlled trials. Diabetes Res. Clin. Pract. 159, 107981 (2020).CAS 
PubMed 

Google Scholar 
99.DeVries, J. H. & Rosenstock, J. DPP-4 inhibitor-related pancreatitis: rare but real! Diabetes Care 40, 161–163 (2017).PubMed 

Google Scholar 
100.Wang, C. Y., Fu, S. H., Yang, R. S. & Hsiao, F. Y. Use of dipeptidyl peptidase-4 inhibitors and the risk of arthralgia: population-based cohort and nested case–control studies. Pharmacoepidemiol. Drug Saf. 28, 500–506 (2019).CAS 
PubMed 

Google Scholar 
101.García-Díez, I. et al. Bullous pemphigoid induced by dipeptidyl peptidase-4 inhibitors. Eight cases with clinical and immunological characterization. Int. J. Dermatol. 57, 810–816 (2018).PubMed 

Google Scholar 
102.Douros, A. et al. Dipeptidyl peptidase 4 inhibitors and the risk of bullous pemphigoid among patients with type 2 diabetes. Diabetes Care 42, 1496–1503 (2019).CAS 
PubMed 

Google Scholar 
103.Koyani, C. N. et al. Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure. Biochem. Pharmacol. 145, 64–80 (2017).CAS 
PubMed 

Google Scholar 
104.Koyani, C. N. et al. Saxagliptin but not sitagliptin inhibits CaMKII and PKC via DPP9 inhibition in cardiomyocytes. Front. Physiol. 9, 1622 (2018).PubMed 
PubMed Central 

Google Scholar 
105.Davies, M. J. et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 61, 2461–2498 (2018).PubMed 

Google Scholar 
106.Seferović, P. M. et al. European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur. J. Heart Fail. 22, 196–213 (2020).PubMed 

Google Scholar 
107.Burkey, B. F. et al. Adverse effects of dipeptidyl peptidases 8 and 9 inhibition in rodents revisited. Diabetes Obes. Metab. 10, 1057–1061 (2008).CAS 
PubMed 

Google Scholar 
108.Williams, R. et al. Cardiovascular safety of vildagliptin in patients with type 2 diabetes: a European multi-database, non-interventional post-authorization safety study. Diabetes Obes. Metab. 19, 1473–1478 (2017).CAS 
PubMed 

Google Scholar 
109.McMurray, J. J. V. et al. Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC Heart. Fail. 6, 8–17 (2018).PubMed 

Google Scholar 
110.Ligueros-Saylan, M., Foley, J. E., Schweizer, A., Couturier, A. & Kothny, W. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of phase II and III clinical trials. Diabetes Obes. Metab. 12, 495–509 (2010).CAS 
PubMed 

Google Scholar 
111.Barbehenn, E., Almashat, S., Carome, M. & Wolfe, S. Hepatotoxicity of alogliptin. Clin. Pharmacokinet. 53, 1055–1056 (2014).PubMed 

Google Scholar 
112.Scheen, A. J. Alogliptin: concern about hepatotoxicity? Clin. Pharmacokinet. 53, 1057–1059 (2014).PubMed 

Google Scholar 
113.Mannucci, E. et al. Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without type 2 diabetes. Diabetes Nutr. Metab. 17, 336–342 (2004).CAS 
PubMed 

Google Scholar 
114.Migoya, E. M. et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin. Pharmacol. Ther. 88, 801–808 (2010).CAS 
PubMed 

Google Scholar 
115.Bahne, E. et al. Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes. JCI Insight 3, 93936 (2018).PubMed 

Google Scholar 
116.Monami, M., Iacomelli, I., Marchionni, N. & Mannucci, E. Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr. Metab. Cardiovasc. Dis. 20, 224–235 (2010).CAS 
PubMed 

Google Scholar 
117.Wang, T., McNeill, A. M., Chen, Y., O’Neill, E. A. & Engel, S. S. Characteristics of elderly patients initiating sitagliptin or non-DPP-4-inhibitor oral antihyperglycemic agents: analysis of a cross-sectional US claims database. Diabetes Ther. 9, 309–315 (2018).CAS 
PubMed 
PubMed Central 

Google Scholar 
118.Barzilai, N. et al. Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Curr. Med. Res. Opin. 27, 1049–1058 (2011).CAS 
PubMed 

Google Scholar 
119.Barnett, A. H. et al. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet 382, 1413–1423 (2013).CAS 
PubMed 

Google Scholar 
120.Strain, W. D., Lukashevich, V., Kothny, W., Hoellinger, M. J. & Paldánius, P. M. Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study. Lancet 382, 409–416 (2013).CAS 
PubMed 

Google Scholar 
121.Leiter, L. A. et al. Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial. Diabetes Care 38, 1145–1153 (2015).CAS 
PubMed 

Google Scholar 
122.Bethel, M. A. et al. Assessing the safety of sitagliptin in older participants in the trial evaluating cardiovascular outcomes with sitagliptin (TECOS). Diabetes Care. 40, 494–501 (2017).PubMed 

Google Scholar 
123.Walker, S. R. et al. Dipeptidyl peptidase-4 inhibitors in chronic kidney disease: a systematic review of randomized clinical trials. Nephron. 136, 85–94 (2017).CAS 
PubMed 

Google Scholar 
124.Spanopoulos, D., Barrett, B., Busse, M., Roman, T. & Poole, C. Prescription of DPP-4 inhibitors to type 2 diabetes mellitus patients with renal impairment: a UK primary care experience. Clin. Ther. 40, 152–154 (2018).CAS 
PubMed 

Google Scholar 
125.Bergman, A. J. et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin. Ther. 28, 55–72 (2006).CAS 
PubMed 

Google Scholar 
126.He, Y. L. et al. Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT. J. Clin. Pharmacol. 47, 633–641 (2007).CAS 
PubMed 

Google Scholar 
127.Christopher, R. et al. Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase-4 inhibitor alogliptin in healthy male subjects. Clin. Ther. 30, 513–527 (2008).CAS 
PubMed 

Google Scholar 
128.Bajaj, H. S. et al. Glycemic improvement with a fixed-dose combination of DPP-4 inhibitor + metformin in patients with type 2 diabetes (GIFT study). Diabetes Obes. Metab. 20, 195–199 (2018).CAS 
PubMed 

Google Scholar 
129.Molina-Vega, M., Muñoz-Garach, A., Fernández-García, J. C. & Tinahones, F. J. The safety of DPP-4 inhibitor and SGLT2 inhibitor combination therapies. Expert Opin. Drug Saf. 17, 815–824 (2018).PubMed 

Google Scholar 
130.Holland, D. Q. & Neumiller, J. J. Alogliptin in combination with metformin and pioglitazone for the treatment of type 2 diabetes mellitus. Diabetes Metab. Syndr. Obes. 7, 277–288 (2014).CAS 
PubMed 
PubMed Central 

Google Scholar 
131.North, E. J. & Newman, J. D. Review of cardiovascular outcomes trials of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Curr. Opin. Cardiol. 34, 687–692 (2019).PubMed 
PubMed Central 

Google Scholar 
132.Buse, J. B. et al. 2019 update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 63, 221–228 (2020).PubMed 

Google Scholar 
133.Zoungas, S. et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol. 5, 431–437 (2017).PubMed 

Google Scholar 
134.Lipinski, C. A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol. 1, 337–341 (2004).CAS 
PubMed 

Google Scholar 
135.Carr, R. D. & Solomon, A. Inhibitors of dipeptidyl peptidase 4 as therapeutic agents for individuals with type 2 diabetes: a 25-year journey. Diabet Med. 33, 718–722 (2020).
Google Scholar 

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