Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the treatment of type 2 diabetes: A systematic review and meta-analysis

Diabetes and Metabolism

Volumn 44, Issue 5, 2018, Pages 393-401

  Cho, Y K ^a   Kang, Y M ^a   Lee, S E ^a   Lee, J ^a   Park, J Y ^a   Lee, W J ^a   Kim, Y J ^a   Jung, C H ^a  

^a University of Ulsan College of Medicine   (South Korea)

Author keywords

DPP4 inhibitor; Meta analysis; SGLT2 inhibitors; Type 2 diabetes

Indexed keywords

ANTIDIABETIC AGENT; CANAGLIFLOZIN; DAPAGLIFLOZIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EMPAGLIFLOZIN; HEMOGLOBIN A1C; LINAGLIPTIN; METFORMIN; PLACEBO; SAXAGLIPTIN; SITAGLIPTIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; TENELIGLIPTIN;

ARTICLE; BODY WEIGHT CHANGE; BODY WEIGHT LOSS; DRUG EFFICACY; DRUG SAFETY; GENITAL TRACT INFECTION; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPOGLYCEMIA; META ANALYSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTEMATIC REVIEW; COMBINATION DRUG THERAPY; TREATMENT OUTCOME;

DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DRUG THERAPY, COMBINATION; HUMANS; HYPOGLYCEMIC AGENTS; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS; TREATMENT OUTCOME;

EID: 85044637701     PISSN: 12623636     EISSN: 18781780     Source Type: Journal    
DOI: 10.1016/j.diabet.2018.01.011     Document Type: Article

References (39)

1. Skyler, J.S., Bakris, G.L., Bonifacio, E., Darsow, T., Eckel, R.H., Groop, L., et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes 66 (2017), 241–255.
2. Sharma, M.D., Potential for combination of dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors for the treatment of type 2 diabetes. Diabetes Obes Metab 17 (2015), 616–621.
3. Scheen, A.J., A review of gliptins for 2014. Expert Opin Pharmacother 16 (2015), 43–62.
4. Dey, J., SGLT2 inhibitor/DPP-4 inhibitor combination therapy – complementary mechanisms of action for management of type 2 diabetes mellitus. Postgrad Med 129 (2017), 409–420.
5. Aschner, P., Kipnes, M.S., Lunceford, J.K., Sanchez, M., Mickel, C., Williams-Herman, D.E., et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 29 (2006), 2632–2637.
6. Rosenstock, J., Aguilar-Salinas, C., Klein, E., Nepal, S., List, J., Chen, R., et al. Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin 25 (2009), 2401–2411.
7. Del Prato, S., Barnett, A.H., Huisman, H., Neubacher, D., Woerle, H.J., Dugi, K.A., Effect of linagliptin monotherapy on glycaemic control and markers of beta-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab 13 (2011), 258–267.
8. 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 38 (2015), 373–375.
9. Ferrannini, G., Hach, T., Crowe, S., Sanghvi, A., Hall, K.D., Ferrannini, E., Energy balance after Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 38 (2015), 1730–1735.
10. Yang, X.P., Lai, D., Zhong, X.Y., Shen, H.P., Huang, Y.L., Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic review and meta-analysis. Eur J Clin Pharmacol 70 (2014), 1149–1158.
11. Zhang, M., Zhang, L., Wu, B., Song, H., An, Z., Li, S., Dapagliflozin treatment for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Res Rev 30 (2014), 204–221.
12. Liakos, A., Karagiannis, T., Athanasiadou, E., Sarigianni, M., Mainou, M., Papatheodorou, K., et al. Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 16 (2014), 984–993.
13. Maruthur, N.M., Tseng, E., Hutfless, S., Wilson, L.M., Suarez-Cuervo, C., Berger, Z., et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 164 (2016), 740–751.
14. Defronzo, R.A., Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58 (2009), 773–795.
15. DeFronzo, R.A., Eldor, R., Abdul-Ghani, M., Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care 36:Suppl 2 (2013), S127–S138.
16. Scheen, A.J., DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects. Expert Opin Drug Metab Toxicol 12 (2016), 1407–1417.
17. Lingvay, I., Sodium Glucose Cotransporter 2 and Dipeptidyl Peptidase-4 Inhibition: promise of a dynamic duo. Endocr Pract 23 (2017), 831–840.
18. Rosenstock, J., Hansen, L., Zee, P., Li, Y., Cook, W., Hirshberg, B., 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 38 (2015), 376–383.
19. Lewin, A., DeFronzo, R.A., Patel, S., Liu, D., Kaste, R., Woerle, H.J., et al. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care 38 (2015), 394–402.
20. DeFronzo, R.A., Lewin, A., Patel, S., Liu, D., Kaste, R., Woerle, H.J., et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care 38 (2015), 384–393.
21. Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gotzsche, P.C., Ioannidis, J.P., et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151 (2009), W65–W94.
22. Tinahones, F.J., Gallwitz, B., Nordaby, M., Gotz, S., Maldonado-Lutomirsky, M., Woerle, H.J., et al. Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: two 24-week randomized, double-blind, double-dummy, parallel-group trials. Diabetes Obes Metab 19 (2017), 266–274.
23. Higgins, J.P., Altman, D.G., Gotzsche, P.C., Juni, P., Moher, D., Oxman, A.D., et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 343, 2011, d5928.
24. Jabbour, S.A., Hardy, E., Sugg, J., Parikh, S., Study, G., 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 37 (2014), 740–750.
25. Kadowaki, T., Inagaki, N., Kondo, K., Nishimura, K., Kaneko, G., Maruyama, N., et al. Efficacy and safety of canagliflozin as add-on therapy to teneligliptin in Japanese patients with type 2 diabetes mellitus: results of a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 19 (2017), 874–882.
26. Mathieu, C., Ranetti, A.E., Li, D., Ekholm, E., Cook, W., Hirshberg, B., 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 38 (2015), 2009–2017.
27. Rodbard, H.W., Seufert, J., Aggarwal, N., Cao, A., Fung, A., Pfeifer, M., et al. Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes mellitus inadequately controlled on Metformin and Sitagliptin. Diabetes Obes Metab 18 (2016), 812–819.
28. Søfteland, E., Meier, J.J., Vangen, B., Toorawa, R., Maldonado-Lutomirsky, M., Broedl, U.C., Empagliflozin as add-on therapy in patients with type 2 Diabetes inadequately controlled with Linagliptin and Metformin: a 24-week randomized, double-blind, parallel-group trial. Diabetes Care 40 (2017), 201–209.
29. Matthaei, S., Catrinoiu, D., Celinski, A., Ekholm, E., Cook, W., Hirshberg, B., 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 38 (2015), 2018–2024.
30. Garber, A.J., Abrahamson, M.J., Barzilay, J.I., Blonde, L., Bloomgarden, Z.T., Bush, M.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 (2016), 84–113.
31. Zinman, B., Initial combination therapy for type 2 diabetes mellitus: is it ready for prime time?. Am J Med 124 (2011), S19–S34.
32. Barnett, A.H., Patel, S., Harper, R., Toorawa, R., Thiemann, S., von Eynatten, M., et al. Linagliptin monotherapy in type 2 diabetes patients for whom metformin is inappropriate: an 18-week randomized, double-blind, placebo-controlled phase III trial with a 34-week active-controlled extension. Diabetes Obes Metab 14 (2012), 1145–1154.
33. Barzilai, N., Guo, H., Mahoney, E.M., Caporossi, S., Golm, G.T., Langdon, R.B., 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 (2011), 1049–1058.
34. Merovci, A., Solis-Herrera, C., Daniele, G., Eldor, R., Fiorentino, T.V., Tripathy, D., et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 124 (2014), 509–514.
35. Schernthaner, G., Schernthaner-Reiter, M.H., How attractive is the combination of a sodium glucose co-transporter 2 inhibitor with a dipeptidyl peptidase 4 inhibitor in the treatment of type 2 diabetes?. Diabetes Obes Metab 17 (2015), 613–615.
36. Roden, M., Weng, J., Eilbracht, J., Delafont, B., Kim, G., Woerle, H.J., et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 1 (2013), 208–219.
37. Abdul-Ghani, M.A., DeFronzo, R.A., Norton, L., Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30–50% of filtered glucose load in humans. Diabetes 62 (2013), 3324–3328.
38. Li, D., Wang, T., Shen, S., Fang, Z., Dong, Y., Tang, H., Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 19 (2017), 348–355.
39. Fadini, G.P., Bonora, B.M., Mayur, S., Rigato, M., Avogaro, A., Dipeptidyl peptidase-4 inhibitors moderate the risk of genitourinary tract infections associated with sodium-glucose co-transporter-2 inhibitors. Diabetes Obes Metab, 2017, 10.1111/dom.13130 [Epub ahead of print].