DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

References

• DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–795.
   PubMed Web of Science ®Google Scholar
• Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58:429–442.
   PubMed Web of Science ®Google Scholar
• Garber AJ, Abrahamson MJ, Barzilay JI, 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.
   PubMed Web of Science ®Google Scholar
• Barnett AH, Charbonnel B, Moses RG, et al. Dipeptidyl peptidase-4 inhibitors in triple oral therapy regimens in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015;31:1919–1931.
   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;127:463–479.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. A review of gliptins for 2014. Exp Opin Pharmacother. 2015;16:43–62.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Safety of dipeptidyl peptidase-4 inhibitors for treating type 2 diabetes. Expert Opin Drug Saf. 2015;14:505–524.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015;75:33–59.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment. Exp Opin Drug Safety. 2015;14:1879–1904.
   PubMed Web of Science ®Google Scholar
• Zaccardi F, Webb DR, Htike ZZ, et al. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obesity Metab. 2016;18: 783–794.
   PubMed Web of Science ®Google Scholar
• Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Reduction in cardiovascular and all-cause mortality in the EMPA-REG OUTCOME trial: a critical analysis. Diabetes Metab. 2016;42:71–76.
   PubMed Web of Science ®Google Scholar
• Sharma MD. Potential for combination of dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors for the treatment of type 2 diabetes. Diabetes Obesity Metab. 2015;17:616–621.
   PubMed Web of Science ®Google Scholar
• Abdul-Ghani M. Where does combination therapy with an SGLT2 inhibitor plus a DPP-4 inhibitor fit in the management of type 2 diabetes? Diabetes Care. 2015;38:373–375.
   PubMed Web of Science ®Google Scholar
• Aronson R. Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus empagliflozin. Curr Med Res Opin. 2015;31:901–911.
   PubMed Web of Science ®Google Scholar
• Woo V. Empagliflozin/linagliptin single-tablet combination: first-in-class treatment option. Int J Clin Pract. 2015;69:1427–1437.
   PubMed Web of Science ®Google Scholar
• Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014;124:509–514.
   PubMed Web of Science ®Google Scholar
• Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124:499–508.
   PubMed Web of Science ®Google Scholar
• Scheen AJ, Paquot N. Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: a review of the clinical evidence. Diabetes Metab. 2014;40:S4–S11.
   PubMed Web of Science ®Google Scholar
• Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37:1526–1534.
   PubMed Web of Science ®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. 2015;132:e121–e122.
   PubMed Web of Science ®Google Scholar
• Paneni F. DPP-4 inhibitors, heart failure and type 2 diabetes: all eyes on safety. Cardiovasc Diagn Ther. 2015;5:471–478.
   PubMed Web of Science ®Google Scholar
• Williams DM, Stephens JW. Combination therapy with saxagliptin and dapagliflozin for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2015;16:2373–2379.
   PubMed Web of Science ®Google Scholar
• Boulton DW, Kasichayanula S, Keung CFA, et al. Simultaneous oral therapeutic and intravenous (1)(4)C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin. Br J Clin Pharmacol. 2013;75:763–768.
   PubMed Web of Science ®Google Scholar
• Vakkalagadda B, Vetter ML, Rana J, et al. Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects. Pharmacol Res Perspect. 2015;3:e00201.
   PubMedGoogle Scholar
• Friedrich C, Metzmann K, Rose P, et al. A randomized, open-label, crossover study to evaluate the pharmacokinetics of empagliflozin and linagliptin after coadministration in healthy male volunteers. Clin Ther. 2013;35:A33–42.
   PubMed Web of Science ®Google Scholar
• Kinoshita S, Kondo K. Evaluation of pharmacokinetic and pharmacodynamic interactions of canagliflozin and teneligliptin in Japanese healthy male volunteers. Expert Opin Drug Metab Toxicol. 2015;11:7–14.
   PubMed Web of Science ®Google Scholar
• Hansen L, Iqbal N, Ekholm E, et al. Postprandial dynamics of plasma glucose, insulin, and glucagon in patients with type 2 diabetes treated with saxagliptin plus dapagliflozin add-on to metformin therapy. Endocr Pract. 2014;20:1187–1197.
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Hansen L, Zee P, et al. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care. 2015;38:376–383.
   PubMed Web of Science ®Google Scholar
• Mathieu C, Ranetti AE, Li D, et al. Randomized, double-blind, phase 3 trial of triple therapy with dapagliflozin add-on to saxagliptin plus metformin in type 2 diabetes. Diabetes Care. 2015;38:2009–2017.
   PubMed Web of Science ®Google Scholar
• Matthaei S, Catrinoiu D, Celinski A, et al. Randomized, double-blind trial of triple therapy with saxagliptin add-on to dapagliflozin plus metformin in patients with type 2 diabetes. Diabetes Care. 2015;38:2018–2024.
   PubMed Web of Science ®Google Scholar
• Kim ES, Deeks ED. Empagliflozin/linagliptin: a review in type 2 diabetes. Drugs. 2015;75:1547–1557.
   PubMed Web of Science ®Google Scholar
• Triplitt C, Solis-Herrera C, Cersosimo E, et al. Empagliflozin and linagliptin combination therapy for treatment of patients with type 2 diabetes mellitus. Expert Opin Pharmacother. 2015;16:2819–2833.
   PubMed Web of Science ®Google Scholar
• Tan X, Hu J, Empagliflozin/linagliptin: combination therapy in patients with type 2 diabetes. Ann Endocrinol (Paris). 2016. published online. doi:10.1016/j.ando.2015.11.003.
   PubMedGoogle Scholar
• Rauch T, Graefe-Mody U, Deacon CF, et al. Linagliptin increases incretin levels, lowers glucagon, and improves glycemic control in type 2 diabetes mellitus. Diabetes Ther. 2012;3:10.
   PubMedGoogle Scholar
• Lewin A, DeFronzo RA, Patel S, et al. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care. 2015;38:394–402.
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Lewin A, Patel S, et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care. 2015;38:384–393.
   PubMed Web of Science ®Google Scholar
• Plosker GL. Canagliflozin: a review of its use in patients with type 2 diabetes mellitus. Drugs. 2014;74:807–824.
   PubMed Web of Science ®Google Scholar
• Fulcher G, Matthews DR, Perkovic V, et al. Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2016;18:82–91.
   PubMed Web of Science ®Google Scholar
• Inagaki N, Kondo K, Yoshinari T, et al. Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: a 52-week open-label study. J Diabetes Investig. 2015;6:210–218.
   PubMed Web of Science ®Google Scholar
• Kadowaki T, Marubayashi F, Yokota S, et al. Safety and efficacy of teneligliptin in Japanese patients with type 2 diabetes mellitus: a pooled analysis of two Phase III clinical studies. Expert Opin Pharmacother. 2015;16:971–981.
   PubMed Web of Science ®Google Scholar
• Scott LJ. Teneligliptin: a review in type 2 diabetes. Clin Drug Investig. 2015;35:765–772.
   PubMed Web of Science ®Google Scholar
• Plosker GL. Sitagliptin: a review of its use in patients with type 2 diabetes mellitus. Drugs. 2014;74:223–242.
   PubMed Web of Science ®Google Scholar
• Kasichayanula S, Liu X, Shyu WC, et al. Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium-glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects. Diabetes Obes Metab. 2011;13:47–54.
   PubMed Web of Science ®Google Scholar
• Smulders RA, Zhang W, Veltkamp SA, et al. No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects. Diabetes Obes Metab. 2012;14:937–943.
   PubMed Web of Science ®Google Scholar
• Kasahara N, Fukase H, Ohba Y, et al. A pharmacokinetic/pharmacodynamic drug-drug interaction study of tofogliflozin (a new SGLT2 inhibitor) and selected anti-type 2 diabetes mellitus drugs. Drug Res. 2016;66:74–81.
   Web of Science ®Google Scholar
• Kumar V, Sahasrabudhe V, Matschke K, et al. Lack of a pharmacokinetic interaction between ertugliflozin and sitagliptin or metformin in healthy subjects. Clin Pharmacol Ther. 2016;99:S47. (Abstract).
   Google Scholar
• Jabbour SA, Hardy E, Sugg J, et al. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care. 2014;37:740–750.
   PubMed Web of Science ®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. Oral presentation at the 76th Scientific Sessions of the American Diabetes Association; 2016 Jun 10–14; New Orleans. Abstract number: 125-LB.
   Google Scholar
• Zambrowicz B, Ding ZM, Ogbaa I, et al. Effects of LX4211, a dual SGLT1/SGLT2 inhibitor, plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes. Clin Ther. 2013;35:273–85 e7.
   PubMed Web of Science ®Google Scholar
• Taylor SI, Blau JE, Rother KI. Perspective: SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab. 2015;100:2849–2852.
   PubMed Web of Science ®Google Scholar
• Li L, Li S, Deng K, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. BMJ. 2016;352:i610.
   PubMed Web of Science ®Google Scholar
• Scheen AJ, Radermecker RP. Addition of incretin therapy to metformin in type 2 diabetes. Lancet. 2010;375:1410–1412.
   PubMed Web of Science ®Google Scholar
• Scheen AJ, Paquot N. Gliptin versus a sulphonylurea as add-on to metformin. Lancet. 2012;380:450–452.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. SGLT2 versus DPP4 inhibitors for type 2 diabetes. Lancet Diabetes Endocrinol. 2013;1:168–170.
   PubMed Web of Science ®Google Scholar
• Thayer S, Chow W, Korrer S, et al. Real-world evaluation of glycemic control among patients with type 2 diabetes mellitus treated with canagliflozin versus dipeptidyl peptidase-4 inhibitors. Curr Med Res Opin. 2016;32:1087–1096.
   PubMed Web of Science ®Google Scholar
• Brietzke SA. Oral antihyperglycemic treatment options for type 2 diabetes mellitus. Med Clin North Am. 2015;99:87–106.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Pharmacokinetics and clinical use of incretin-based therapies in patients with chronic kidney disease and type 2 diabetes. Clin Pharmacokinet. 2015;54:1–21.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Pharmacokinetics, pharmacodynamics and clinical use of SGLT2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease. Clin Pharmacokinet. 2015;54:691–708.
   PubMed Web of Science ®Google Scholar
• Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016. [Epub ahead of print].
   Web of Science ®Google Scholar
• Scheen AJ, Charbonnel B. Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: a critical reappraisal. Diabetes Metab. 2014;40:176–185.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Precision medicine: the future in diabetes care? Diabetes Res Clin Pract. 2016;117:12–21.
   PubMed Web of Science ®Google Scholar
• Charokopou M, McEwan P, Lister S, et al. Cost-effectiveness of dapagliflozin versus DPP-4 inhibitors as an add-on to metformin in the treatment of type 2 diabetes mellitus from a UK healthcare system perspective. BMC Health Serv Res. 2015;15:496.
   PubMed Web of Science ®Google Scholar
• Geng J, Yu H, Mao Y, et al. Cost effectiveness of dipeptidyl peptidase-4 inhibitors for type 2 diabetes. Pharmacoeconomics. 2015;33:581–597.
   PubMed Web of Science ®Google Scholar
• Lopez JMS, Macomson B, Ektare V, et al. Evaluating drug cost per response with SGLT2 inhibitors in patients with type 2 diabetes mellitus. Am Health Drug Benefits. 2015;8:309–318.
   PubMed Web of Science ®Google Scholar