An update on DPP-4 inhibitors in the management of type 2 diabetes

References

• IDF Diabetes Atlas - 7th edition. [Cited 2016 Nov 12]. Available from: http://www.diabetesatlas.org/
   Google Scholar
• American Diabetes Association. Approaches to glycemic treatment. Diabetes Care. 2016;39(Suppl. 1):S52–S59.
   PubMedGoogle Scholar
• Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17(6):819–837.
   PubMed Web of Science ®Google Scholar
• Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol. 2009;5(5):262–269.
   PubMed Web of Science ®Google Scholar
• Cahn A, Raz I. Emerging gliptins for type 2 diabetes. Expert Opin Emerg Drugs. 2013;18(2):245–258.
   PubMed Web of Science ®Google Scholar
• Holst JJ, Knop FK, Vilsbøll T, et al. Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care. 2011;34(Suppl 2):S251–257.
   PubMed Web of Science ®Google Scholar
• Nauck MA. Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med. 2011 Jan;124(1 Suppl):S3–S18.
   PubMed Web of Science ®Google Scholar
• Gong Q, Rajagopalan S, Zhong J. Dpp4 inhibition as a therapeutic strategy in cardiometabolic disease: incretin-dependent and -independent function. Int J Cardiol. 2015 Oct 15;197:170–179.
   PubMed Web of Science ®Google Scholar
• Zhong J, Rao X, Rajagopalan S. An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. Atherosclerosis. 2013 Feb;226(2):305–314.
   PubMed Web of Science ®Google Scholar
• Monami M, Ahrén B, Dicembrini I, et al. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2013 Feb;15(2):112–120.
   PubMed Web of Science ®Google Scholar
• Patil HR, Al Badarin FJ, Al Shami HA, et al. Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol. 2012 Sep 15;110(6):826–833.
   PubMed Web of Science ®Google Scholar
• Davidson MH. Potential impact of dipeptidyl peptidase-4 inhibitors on cardiovascular pathophysiology in type 2 diabetes mellitus. Postgrad Med. 2014 May;126(3):56–65.
   PubMed Web of Science ®Google Scholar
• Seufert J, Gallwitz B. The extra-pancreatic effects of GLP-1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems. Diabetes Obes Metab. 2014 Aug;16(8):673–688.
   PubMed Web of Science ®Google Scholar
• Shah Z, Kampfrath T, Deiuliis JA, et al. Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation. 2011 Nov 22;124(21):2338–2349.
   PubMed Web of Science ®Google Scholar
• Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–1326.
   PubMed Web of Science ®Google Scholar
• White WB, Cannon CP, Heller SR, et al.; for the EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–1335.
   PubMed Web of Science ®Google Scholar
• Green JB, Bethel MA, Armstrong PW, et al.; TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;373(3):232–242.
   PubMed Web of Science ®Google Scholar
• Savarese G, Perrone-Filardi P, D’Amore C, et al. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in diabetic patients: a meta-analysis. Int J Cardiol. 2015 Feb 15;181:239–244.
   PubMed Web of Science ®Google Scholar
• Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375(4):311–322.
   PubMed Web of Science ®Google Scholar
• Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016 Sep;15.
   Google Scholar
• Skyler JS, Bergenstal R, Bonow RO, et al. American Diabetes Association; American College of Cardiology Foundation; American Heart Association. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care. 2009;32(1):187–192.
   PubMed Web of Science ®Google Scholar
• Hayward RA, Reaven PD, Wiitala WL, et al.; VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;372(23):2197–2206.
   PubMed Web of Science ®Google Scholar
• Zoungas S, Chalmers J, Neal B, et al.; ADVANCE-ON Collaborative Group. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med 2014;371(15):1392–1406.
   PubMed Web of Science ®Google Scholar
• Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405–412.
   PubMed Web of Science ®Google Scholar
• American Diabetes Association. Glycemic targets. Diabetes Care. 2016;39(Suppl 1):S39–46.
   PubMed Web of Science ®Google Scholar
• Cahn A, Raz I, Kleinman Y, et al. Clinical assessment of individualized glycemic goals in patients with type 2 diabetes: formulation of an algorithm based on a survey among leading worldwide diabetologists. Diabetes Care. 2015;38(12):2293–2300.
   PubMed Web of Science ®Google Scholar
• Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–1439.
   PubMed Web of Science ®Google Scholar
• Salvo F, Moore N, Arnaud M, et al. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. BMJ. 2016;353:i2231.
   PubMed Web of Science ®Google Scholar
• Cahn A, Raz I, Mosenzon O, et al. Predisposing factors for any and major hypoglycemia with saxagliptin versus placebo and overall: analysis from the SAVOR-TIMI 53 trial. Diabetes Care. 2016;39(8):1329–1337.
   PubMed Web of Science ®Google Scholar
• Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA. 2016;316(3):313–324.
   PubMed Web of Science ®Google Scholar
• Lingvay I, Manghi FP, García-Hernández P, et al.; DUAL V Investigators. Effect of insulin glargine up-titration vs insulin degludec/liraglutide on glycated hemoglobin levels in patients with uncontrolled type 2 diabetes: the DUAL V randomized clinical trial. JAMA 2016;315(9):898–907.
   PubMed Web of Science ®Google Scholar
• Conway BN, May ME, Fischl A, et al. Cause‐specific mortality by race in low‐income black and white people with type 2 diabetes. Diabetic Med. 2015;32(1):33–41.
   PubMed Web of Science ®Google Scholar
• Geiss LS, Herman WH, Smith PJ. Mortality in non-insulin-dependent diabetes. Harris MI, Cowie CC, Stern MP, et al. eds. Diabetes in America. 2nd ed. Bethesda (MD): National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 1995. p. 233–257. NIH publication 95-1468.
   Google Scholar
• Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457–2471.
   PubMed Web of Science ®Google Scholar
• Guidance for IndustryDiabetes Mellitus — EvaluatingCardiovascular Risk in NewAntidiabetic Therapies toTreat Type 2 Diabetes. [cited 2016 Nov 12]. Available from: http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm071627.pdf
   Google Scholar
• [Cited 2016 Nov 12] Available from: www.clinicaltrials.gov trials identifier: NCT01897532, NCT01243424, NCT01703208
   Google Scholar
• Scirica BM, Braunwald E, Raz I, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130:1579–1588.
   PubMed Web of Science ®Google Scholar
• Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385:2067–2076.
   PubMed Web of Science ®Google Scholar
• McMurray J. The vildagliptin in ventricular dysfunction diabetes trial (VIVIDD). Lisbon: Heart Failure Congress, European Society 2013; 2013 May.
   Google Scholar
• Toh S, Hampp C, Reichman ME, et al. Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Ann Intern Med. 2016;164(11):705–714.
   PubMed Web of Science ®Google Scholar
• Hippisley-Cox J, Coupland C. Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care. BMJ. 2016 Jul;12(354):i3477.
   Web of Science ®Google Scholar
• Filion KB, Azoulay L, Platt RW, et al., CNODES Investigators. A multicenter observational study of incretin-based drugs and heart failure. N Engl J Med. 2016 Mar 24;374(12):1145–1154.
   PubMed Web of Science ®Google Scholar
• Schernthaner G, Cahn A, Raz I. Is the use of DPP-4 inhibitors associated with an increased risk for heart failure? Lessons from EXAMINE, SAVOR and TECOS. Diabetes Care. 2016;39(Suppl 2):S210–208.
   PubMed Web of Science ®Google Scholar
• Mosenzon O, Wei C, Davidson J, et al. Incidence of fractures in patients with type 2 diabetes in the SAVOR-TIMI 53 trial. Diabetes Care. 2015;38(11):2142–2150.
   PubMed Web of Science ®Google Scholar
• Leiter LA, Teoh H, Mosenzon O, et al.; SAVOR-TIMI 53 Steering Committee, Investigators. Frequency of cancer events with saxagliptin in the SAVOR-TIMI 53 trial. Diabetes Obes Metab 2016;18(2):186–190.
   PubMed Web of Science ®Google Scholar
• Raz I, Bhatt DL, Hirshberg B, et al. Incidence of pancreatitis and pancreatic cancer in a randomized controlled multicenter trial (SAVOR-TIMI 53) of the dipeptidyl peptidase-4 inhibitor saxagliptin. Diabetes Care. 2014;37(9):2435–2441.
   PubMed Web of Science ®Google Scholar
• Faillie JL, Azoulay L, Patenaude V, et al. Incretin based drugs and risk of acute pancreatitis in patients with type 2 diabetes: cohort study. BMJ. 2014;348:g2780.
   PubMed Web of Science ®Google Scholar
• Thomsen RW, Pedersen L, Møller N, et al. Incretin-based therapy and risk of acute pancreatitis: a nationwide population-based case-control study. Diabetes Care. 2015;38(6):1089–1098.
   PubMed Web of Science ®Google Scholar
• Pfeffer MA, Claggett B, Diaz R, et al.; ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 2015;373(23):2247–2257.
   PubMed Web of Science ®Google Scholar
• Rehman MB, Tudrej BV, Soustre J, et al. Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials. Diabetes Metab. 2016 Oct 10;pii: S1262-3636(16)30505-5. [Epub ahead of print].
   PubMedGoogle Scholar
• Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 2011 Jul;141(1):150–156.
   PubMed Web of Science ®Google Scholar
• Available from: http://www.cdc.gov/diabetes/statistics/prev/national/figbyage.htm
   Google Scholar
• Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care. 2012;35(12):2650–2664.
   PubMed Web of Science ®Google Scholar
• Pharmaprojects. copyright to Citeline Drug Intelligence (an informa business) search results: sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin, teneligliptin, anagliptin, gemigliptin, trelagliptin, omarigliptin, gosogliptin, evogliptin.
   Google Scholar
• Merck Provides Update on Combination Medicine JUVISYNC™ (sitagliptin and simvastatin) Tablets. [Cited 2016 Nov 12]. Available from: http://www.mercknewsroom.com/news/company-statements/merck-provides-update-combination-medicine-juvisync-sitagliptin-and-simvasta
   Google Scholar
• Application number: 202343Orig1s000 MEDICAL REVIEW(S). [cited 2016 Nov 12]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202343Orig1s000MedR.pdf
   Google Scholar
• Leiter LA, Teoh H, Braunwald E, et al.; SAVOR-TIMI 53 Steering Committee and Investigators. Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial. Diabetes Care 2015;38(6):1145–1153.
   PubMed Web of Science ®Google Scholar
• Barnett AH, Huisman H, Jones R, 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. 2013;382(9902):1413–1423.
   PubMed Web of Science ®Google Scholar
• Sicras-Mainar A, Navarro-Artieda R. Use of metformin and vildagliptin for treatment of type 2 diabetes in the elderly. Drug Des Devel Ther. 2014;8:811–818.
   PubMed Web of Science ®Google Scholar
• Tada Y, Kanazawa I, Notsu M, et al. Long-term efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus. Intern Med. 2016;55(10):1275–1278.
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Wilson C, Fleck P. Alogliptin versus glipizide monotherapy in elderly type 2 diabetes mellitus patients with mild hyperglycaemia: a prospective, double-blind, randomized, 1-year study. Diabetes Obes Metab. 2013;15(10):906–914.
   PubMed Web of Science ®Google Scholar
• Thomas MC, Paldánius PM, Ayyagari R, et al. Systematic literature review of DPP-4 inhibitors in patients with type 2 diabetes mellitus and renal impairment. Diabetes Ther. 2016 Aug;8.
   Google Scholar
• Cooper ME, Perkovic V, McGill JB, et al. Kidney disease end points in a pooled analysis of individual patient-level data from a large clinical trials program of the dipeptidyl peptidase 4 inhibitor linagliptin in type 2 diabetes. Am J Kidney Dis. 2015;66(3):441–449.
   PubMed Web of Science ®Google Scholar
• Mosenzon O, Leibowitz G, Bhatt DL, et al. Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial. Diabetes Care. Oct 17. pii: dc160621. [Epub ahead of print]
   Google Scholar
• Weng W, Liang Y, Kimball ES, et al. Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases, 2007 vs 2012: findings from a large US healthcare claims database analysis. J Med Econ. 2016;19(7):655–662.
   PubMed Web of Science ®Google Scholar
• Kohro T, Yamazaki T, Sato H, et al. Trends in antidiabetic prescription patterns in Japan from 2005 to 2011. Int Heart J. 2013;54(2):93–97.
   PubMed Web of Science ®Google Scholar
• EvaluatePharma® World Preview 2015. Outlook to 2020, 8th Edition. 2015 June, London, UK. Available from: www.evaluategroup.com/WP2015
   Google Scholar
• Wanner C, Inzucchi SE, Lachin JM, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016;375(4):323–334.
   PubMed Web of Science ®Google Scholar
• Zinman B, Wanner C, Lachin JM, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373(22):2117–2128.
   PubMed Web of Science ®Google Scholar
• Consensus statement by the american association ofclinical endocrinologists and american college ofendocrinology on the comprehensive type 2 diabetesmanagement algorithm. [cited 2016 Nov 12]. Available from: https://www.aace.com/sites/all/files/diabetes-algorithm-executive-summary.pdf
   Google Scholar
• [Cited 2016 Nov 12]. Available from: www.clinicaltrials.gov trial identifier: NCT00730275, NCT01525225, NCT01342484
   Google Scholar
• Abdul-Ghani MA, Puckett C, Triplitt C, et al. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. results from the efficacy and durability of initial combination therapy for type 2 diabetes (EDICT): a randomized trial. Diabetes Obes Metab. 2015;17(3):268–275.
   PubMed Web of Science ®Google Scholar
• Cahn A, Cefalu WT. Clinical considerations for use of initial combination therapy in type 2 diabetes. Diabetes Care. 2016;39(Suppl 2):S137S145.
   Google Scholar
• Wu D, Li L, Liu C. Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Obes Metab. 2014;16(1):30–37.
   PubMed Web of Science ®Google Scholar
• Migoya EM, Bergeron R, Miller JL, 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. 2010 Dec;88(6):801–808.
   PubMed Web of Science ®Google Scholar
• Maida A, Lamont BJ, Cao X, et al. Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice. Diabetologia. 2011 Feb;54(2):339–349.
   PubMed Web of Science ®Google Scholar
• Guthrie RM. Clinical use of dipeptidyl peptidase-4 and sodium-glucose cotransporter 2 inhibitors in combination therapy for type 2 diabetes mellitus. Postgrad Med. 2015;127(5):463–479.
   PubMed Web of Science ®Google Scholar
• Sinclair AJ, Bode B, Harris S, et al. Efficacy and safety of canagliflozin in individuals aged 75 and older with type 2 diabetes mellitus: a pooled analysis. J Am Geriatr Soc. 2016 Mar;64(3):543–552.
   PubMed Web of Science ®Google Scholar
• Hedrington MS, Davis SN. Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):613–623.
   PubMed Web of Science ®Google Scholar
• Wang B, Choudhry NK, Gagne JJ, et al. Availability and utilization of cardiovascular fixed-dose combination drugs in the United States. Am Heart J. 2015;169(3):379–386.e1.
   PubMed Web of Science ®Google Scholar
• Available from: http://www.mercknewsroom.com/news/company-statements/merck-provides-update-filing-plans-omarigliptin-investigational-dpp-4-inhibi
   Google Scholar
• Pharmaprojects. copyright to Citeline Drug Intelligence (an informa business) search results: retagliptin, sitagliptin+ertugliflozin, sitagliptin+ipragliflozin, teneligliptin+canagliflozin, gemigliptin+rosuvastatin.
   Google Scholar
• Deacon CF, Lebovitz HE. Comparative review of dipeptidyl peptidase-4 inhibitors and sulphonylureas. Diabetes Obes Metab. 2016 Apr;18(4):333–347.
   PubMed Web of Science ®Google Scholar
• Ram Najar K, Haq W, Katti SB. Discovery of 17 gliptins in 17-years of research for the treatment of type 2 diabetes: a synthetic overview. Chem Biol Interface. 2014;4:137–162.
   Google Scholar
• Mascitti V, Maurer TS, Robinson RP, et al. Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors. J Med Chem. 2011 Apr 28;54(8):2952–2960.
   PubMed Web of Science ®Google Scholar
• Nomura S, Sakamaki S, Hongu M, et al. Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus. J Med Chem. 2010 Sep 9;53(17):6355–6360.
   PubMed Web of Science ®Google Scholar
• Imamura M, Nakanishi K, Suzuki T, et al. Discovery of ipragliflozin (ASP1941): a novel C-glucoside with benzothiophene structure as a potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus. Bioorg Med Chem. 2012 May 15;20(10):3263–3279.
   PubMed Web of Science ®Google Scholar
• [Cited 2016 Nov 12] Available from: www.clinicaltrials.gov trial identifier: NCT01969318, NCT01969357
   Google Scholar
• Pan C, Lu J, Li X, et al. Efficacy and safety of retagliptin in chinese patients with Type 2 diabetes mellitus. ADA. 2015;1188–P.
   Google Scholar
• [Cited 2016 Nov 12]. Available from: www.clinicaltrials.gov trial identifier: NCT01970046
   Google Scholar
• Hengrui Medicine Alert:Retagliptin filing has been withdrawn. [cited 2016 Nov 12]. Available from: http://app.finance.china.com.cn/report/detail.php?id=3203075
   Google Scholar
• Eldor R, Pratley R, Golm G, et al. Effect of ertugliflozin plus sitagliptin on glycemic control vs. either treatment alone in subjects with T2DM inadequately controlled with metformin. ADA. 2016;125–LB.
   Google Scholar
• [Cited 2016 Nov 12]. Available from: www.clinicaltrials.gov trial identifier: NCT02577016, NCT02577003, NCT02564211
   Google Scholar
• [Cited 2016 Nov 12]. Available from: www.clinicaltrials.gov trial identifier: NCT02354235, NCT02354222, NCT02220907
   Google Scholar
• Cui J, Philo L, Nguyen P, et al. Sitagliptin vs. placebo for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol. 2016;65(2):369–376.
   PubMed Web of Science ®Google Scholar
• Dhindsa S, Jialal I. Potential anti-atherosclerotic effects of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus. Curr Diab Rep. 2014;14(2):463.
   PubMed Web of Science ®Google Scholar
• Griffin KJ, Thompson PA, Gottschalk M, et al. Combination therapy with sitagliptin and lansoprazole in patients with recent-onset type 1 diabetes (REPAIR-T1D): 12-month results of a multicentre, randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2014;2(9):710–718.
   PubMed Web of Science ®Google Scholar
• Kaku K, Kadowaki T, Terauchi Y, et al. Sitagliptin improves glycaemic excursion after a meal or after an oral glucose load in Japanese subjects with impaired glucose tolerance. Diabetes Obes Metab. 2015 Nov;17(11):1033–1041.
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Foley JE, Rendell M, et al. Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance. Diabetes Care. 2008 Jan;31(1):30–35.
   PubMed Web of Science ®Google Scholar
• Bock G, Dalla Man C, Micheletto F, et al. The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. Clin Endocrinol (Oxf). 2010 Aug;73(2):189–196.
   PubMed Web of Science ®Google Scholar
• Osei E, Fonville S, Zandbergen AA, et al. Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic stroke (MAAS): study protocol for a randomized controlled trial. Trials. 2015 Aug 5;16(1):332.
   PubMed Web of Science ®Google Scholar
• Naidoo P, Wing J, Rambiritch V. Effect of sitagliptin and metformin on prediabetes progression to Type 2 diabetes – a randomized, double-blind, double-arm, multicenter clinical trial: protocol for the Sitagliptin and metformin in PreDiabetes (SiMePreD) study. Eysenbach G, ed. JMIR Res Protoc. 2016;5(3):e145. DOI:10.2196/resprot.5073.
   PubMed Web of Science ®Google Scholar