Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials.

Scheen, André

doi:10.1016/j.diabet.2020.01.002

Article (Scientific journals)

Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials.

Scheen, André

2020 • In Diabetes and Metabolism

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/246846

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10.1016/j.diabet.2020.01.002

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32007623

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Keywords :

DPP-4 inhibitor; Glucose control; HbA1c; Metformin; SGLT2 inhibitor; Type 2 diabetes

Abstract :

[en] AIMS: This study compared the reduction of glycated haemoglobin (HbA1c) with sodium-glucose cotransporter type-2 inhibitors (SGLT2is) vs. dipeptidyl peptidase-4 inhibitors (DPP-4is) as add-ons to metformin in patients with type 2 diabetes mellitus (T2DM), with a specific focus on HbA1c changes according to baseline HbA1c. MATERIALS AND METHODS: Electronic databases were scrutinized for randomized controlled trials (RCTs) evaluating the reduction of HbA1c from baseline (Delta HbA1c) with an SGLT2i or DPP-4i in patients with T2DM not well controlled by metformin monotherapy. The endpoint was Delta HbA1c using both indirect and direct comparisons. RESULTS: Overall, Delta HbA1c was slightly greater with SGLT2is (-0.80+/-0.20% from 8.03+/-0.35%; 44 analyses, 29 RCTs, 15 with two doses, n=9321) than with DPP-4is (-0.71+/-0.23% from 8.05+/-0.43%; 61 analyses, 59 RCTs, n=17,914; P=0.0354). When the mean baseline HbA1c was<8% ([64mmol/mol] 7.79+/-0.15% vs. 7.71+/-0.23%), Delta HbA1c averaged -0.735+/-0.17% vs. -0.62+/-0.16% (P=0.0117) with SGLT2is vs. DPP-4is, respectively. However, this difference vanished when the mean baseline HbA1c was>/=8% (-0.87+/-0.22% from 8.27+/-0.32% with SGLT2is vs. -0.80+/-0.24% from 8.35+/-0.33% with DPP-4is; P=0.2756). The relationship between Delta HbA1c and baseline HbA1c was only slightly stronger with SGLT2is (slope: -0.39, r(2)=-0.43; P<0.0001) than with DPP-4is (slope: -0.26, r(2)=-0.25; P<0.0001). CONCLUSION: Because of the small difference in Delta HbA1c whatever the baseline HbA1c level with SGLT2is vs. DPP-4is as add-ons to metformin, choosing between these glucose-lowering agents in clinical practice should be based on other efficacy criteria (such as weight and blood pressure changes, cardiovascular and renal protection) or on safety profiles rather than on HbA1c levels.

Disciplines :

Endocrinology, metabolism & nutrition
Pharmacy, pharmacology & toxicology

Author, co-author :

Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques

Language :

English

Title :

Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials.

Publication date :

2020

Journal title :

Diabetes and Metabolism

ISSN :

1262-3636

eISSN :

1878-1780

Peer reviewed :

Peer Reviewed verified by ORBi

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since 23 April 2020

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Bibliography

Wang, Z., Sun, J., Han, R., Fan, D., Dong, X., Luan, Z., et al. Efficacy and safety of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as monotherapy or add-on to metformin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Diab Obes Metab 20 (2018), 113–120.
Mishriky, B.M., Tanenberg, R.J., Sewell, K.A., Cummings, D.M., Comparing SGLT-2 inhibitors to DPP-4 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. Diab Metab 44 (2018), 112–120.
Jingfan, Z., Ling, L., Cong, L., Ping, L., Yu, C., Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis. Arch Endocrinol Metab 63 (2019), 478–486.
Liu, Y., Hong, T., Combination therapy of dipeptidyl peptidase-4 inhibitors and metformin in type 2 diabetes: rationale and evidence. Diab Obes Metab 16 (2014), 111–117.
Omar, B., Ahren, B., Pleiotropic mechanisms for the glucose-lowering action of DPP-4 inhibitors. Diabetes 63 (2014), 2196–2202.
Scheen, A.J., Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 75 (2015), 33–59.
DeFronzo, R.A., Norton, L., Abdul-Ghani, M., Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nature Rev Nephrol 13 (2017), 11–26.
Scheen, A.J., Cardiovascular effects of new oral glucose-lowering agents: DPP-4 and SGLT-2 inhibitors. Circ Res 122 (2018), 1439–1459.
Scheen, A.J., Series:, Implications of the recent CVOTs in Type 2 diabetes: impact on guidelines: the endocrinologist point of view. Diab Res Clin Pract, 2019, 10.1016/j.diabres.2019.05.005 [Epub ahead of print. Epub: May 17. pii: S0168-8227(19)30607-2].
Davies, M.J., D'Alessio, D.A., Fradkin, J., Kernan, W.N., Mathieu, C., Mingrone, G., 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 (2018), 2461–2498.
Mearns, E.S., Sobieraj, D.M., White, C.M., Saulsberry, W.J., Kohn, C.G., Doleh, Y., et al. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. PLoS One, 10, 2015, e0125879.
Scheen, A.J., SGLT2 versus DPP4 inhibitors for type 2 diabetes. Lancet Diab Endocrinol 1 (2013), 168–170.
Goldenberg, R.M., Choosing dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, or both, as add-ons to metformin: patient baseline characteristics are crucial. Clin Ther 39 (2017), 2438–2447.
DeFronzo, R.A., Stonehouse, A.H., Han, J., Wintle, M.E., Relationship of baseline HbA1c and efficacy of current glucose-lowering therapies: a meta-analysis of randomized clinical trials. Diab Med 27 (2010), 309–317.
Henry, R.R., Buse, J.B., Sesti, G., Davies, M.J., Jensen, K.H., Brett, J., et al. Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program. Endocr Pract 17 (2011), 906–913.
DeFronzo, R.A., Ferrannini, E., Schernthaner, G., Hantel, S., Elsasser, U., Lee, C., et al. Slope of change in HbA1c from baseline with empagliflozin compared with sitagliptin or glimepiride in patients with type 2 diabetes. Endocrinol Diab Metab, 1, 2018, e00016.
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 Diab Endocrinol 1 (2013), 208–219.
Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., Group, P., Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151 (2009), 264–269 [W64].
Bailey, C.J., Gross, J.L., Pieters, A., Bastien, A., List, J.F., Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet 375 (2010), 2223–2233.
Nauck, M.A., Del Prato, S., Meier, J.J., Duran-Garcia, S., Rohwedder, K., Elze, M., et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diab Care 34 (2011), 2015–2022.
Bolinder, J., Ljunggren, O., Kullberg, J., Johansson, L., Wilding, J., Langkilde, A.M., et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97 (2012), 1020–1031.
Rosenstock, J., Aggarwal, N., Polidori, D., Zhao, Y., Arbit, D., Usiskin, K., et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diab Care 35 (2012), 1232–1238.
Cefalu, W.T., Leiter, L.A., Yoon, K.H., Arias, P., Niskanen, L., Xie, J., et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 (2013), 941–950.
Bailey, C.J., Gross, J.L., Hennicken, D., Iqbal, N., Mansfield, T.A., List, J.F., Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial. BMC Med, 11, 2013, 43.
Wilding, J.P., Ferrannini, E., Fonseca, V.A., Wilpshaar, W., Dhanjal, P., Houzer, A., Efficacy and safety of ipragliflozin in patients with type 2 diabetes inadequately controlled on metformin: a dose-finding study. Diab Obes Metab 15 (2013), 403–409.
Rosenstock, J., Seman, L.J., Jelaska, A., Hantel, S., Pinnetti, S., Hach, T., et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diab Obes Metab 15 (2013), 1154–1160.
Lavalle-Gonzalez, F.J., Januszewicz, A., Davidson, J., Tong, C., Qiu, R., Canovatchel, W., et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 56 (2013), 2582–2592.
Ridderstrale, M., Andersen, K.R., Zeller, C., Kim, G., Woerle, H.J., Broedl, U.C., et al. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diab Endocrinol 2 (2014), 691–700.
Haring, H.U., Merker, L., Seewaldt-Becker, E., Weimer, M., Meinicke, T., Broedl, U.C., et al. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diab Care 37 (2014), 1650–1659.
Kashiwagi, A., Kazuta, K., Goto, K., Yoshida, S., Ueyama, E., Utsuno, A., Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study. Diab Obes Metab 17 (2015), 304–308.
Ji, L., Han, P., Liu, Y., Yang, G., Dieu Van, N.K., Vijapurkar, U., et al. Canagliflozin in Asian patients with type 2 diabetes on metformin alone or metformin in combination with sulphonylurea. Diab Obes Metab 17 (2015), 23–31.
Schumm-Draeger, P.M., Burgess, L., Koranyi, L., Hruba, V., Hamer-Maansson, J.E., de Bruin, T.W., Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial. Diab Obes Metab 17 (2015), 42–51.
Ross, S., Thamer, C., Cescutti, J., Meinicke, T., Woerle, H.J., Broedl, U.C., Efficacy and safety of empagliflozin twice daily versus once daily in patients with type 2 diabetes inadequately controlled on metformin: a 16-week, randomized, placebo-controlled trial. Diab Obes Metab 17 (2015), 699–702.
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. Diab Care 38 (2015), 376–383.
Rosenstock, J., Cefalu, W.T., Lapuerta, P., Zambrowicz, B., Ogbaa, I., Banks, P., et al. Greater dose-ranging effects on A1C levels than on glucosuria with LX4211, a dual inhibitor of SGLT1 and SGLT2, in patients with type 2 diabetes on metformin monotherapy. Diab Care 38 (2015), 431–438.
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. Diab Care 38 (2015), 384–393.
Amin, N.B., Wang, X., Jain, S.M., Lee, D.S., Nucci, G., Rusnak, J.M., Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin. Diab Obes Metab 17 (2015), 591–598.
Yang, W., Han, P., Min, K.W., Wang, B., Mansfield, T., T'Joen, C., et al. Efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes after metformin failure: a randomized controlled trial. J Diab 8 (2016), 796–808.
Lu, C.H., Min, K.W., Chuang, L.M., Kokubo, S., Yoshida, S., Cha, B.S., Efficacy, safety, and tolerability of ipragliflozin in Asian patients with type 2 diabetes mellitus and inadequate glycemic control with metformin: results of a phase 3 randomized, placebo-controlled, double-blind, multicenter trial. J Diab Investig 7 (2016), 366–373.
Frias, J.P., Guja, C., Hardy, E., Ahmed, A., Dong, F., Ohman, P., et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diab Endocrinol 4 (2016), 1004–1016.
Rosenstock, J., Frias, J., Pall, D., Charbonnel, B., Pascu, R., Saur, D., et al. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET). Diab Obes Metab 20 (2018), 520–529.
Shestakova, M.V., Wilding, J.P.H., Wilpshaar, W., Tretter, R., Orlova, V.L., Verbovoy, A.F., A phase 3 randomized placebo-controlled trial to assess the efficacy and safety of ipragliflozin as an add-on therapy to metformin in Russian patients with inadequately controlled type 2 diabetes mellitus. Diab Res Clin Pract 146 (2018), 240–250.
Pratley, R.E., Eldor, R., Raji, A., Golm, G., Huyck, S.B., Qiu, Y., et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: the VERTIS FACTORIAL randomized trial. Diab Obes Metab 20 (2018), 1111–1120.
Muller-Wieland, D., Kellerer, M., Cypryk, K., Skripova, D., Rohwedder, K., Johnsson, E., et al. Efficacy and safety of dapagliflozin or dapagliflozin plus saxagliptin versus glimepiride as add-on to metformin in patients with type 2 diabetes. Diab Obes Metab 20 (2018), 2598–2607.
Hollander, P., Liu, J., Hill, J., Johnson, J., Jiang, Z.W., Golm, G., et al. Ertugliflozin compared with glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin: the VERTIS SU randomized study. Diab Ther 9 (2018), 193–207.
Lingvay, I., Catarig, A.-M., Frias, J.P., Kumar, H., Lausvig, N.L., Le Roux, C.W., et al. Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, randomised, controlled trial. Lancet Diab Endocrinol 7 (2019), 834–844.
Rodbard, H.W., Rosenstock, J., Canani, L.H., Deerochanawong, C., Gumprecht, J., Lindberg, S.O., et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: the PIONEER 2 trial. Diab Care 42 (2019), 2272–2281.
Ahren, 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. Diab Care 27 (2004), 2874–2880.
Charbonnel, B., Karasik, A., Liu, J., Wu, M., Meininger, G., Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diab Care 29 (2006), 2638–2643.
Bosi, E., Camisasca, R.P., Collober, C., Rochotte, E., Garber, A.J., Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diab Care 30 (2007), 890–895.
Goldstein, B.J., Feinglos, M.N., Lunceford, J.K., Johnson, J., Williams-Herman, D.E., Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diab Care 30 (2007), 1979–1987.
Nauck, M.A., Meininger, G., Sheng, D., Terranella, L., Stein, P.P., Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diab Obes Metab 9 (2007), 194–205.
DeFronzo, R.A., Fleck, P.R., Wilson, C.A., Mekki, Q., Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study. Diab Care 31 (2008), 2315–2317.
Scott, R., Loeys, T., Davies, M.J., Engel, S.S., Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes. Diab Obes Metab 10 (2008), 959–969.
Raz, I., Chen, Y., Wu, M., Hussain, S., Kaufman, K.D., Amatruda, J.M., et al. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes. Curr Med Res Opin 24 (2008), 537–550.
Goodman, M., Thurston, H., Penman, J., Efficacy and tolerability of vildagliptin in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Horm Metab Res 41 (2009), 368–373.
Nauck, M.A., Ellis, G.C., Fleck, P.R., Wilson, C.A., Mekki, Q., Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study. Int J Clin Pract 63 (2009), 46–55.
DeFronzo, R.A., Hissa, M.N., Garber, A.J., Luiz Gross, J., Yuyan Duan, R., Ravichandran, S., et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diab Care 32 (2009), 1649–1655.
Ferrannini, E., Fonseca, V., Zinman, B., Matthews, D., Ahren, B., Byiers, S., et al. Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. Diab Obes Metab 11 (2009), 157–166.
Blonde, L., Dagogo-Jack, S., Banerji, M.A., Pratley, R.E., Marcellari, A., Braceras, R., et al. Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial – A primary care, type 2 diabetes study. Diab Obes Metab 11 (2009), 978–986.
Bolli, G., Dotta, F., Colin, L., Minic, B., Goodman, M., Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin. Diab Obes Metab 11 (2009), 589–595.
Filozov, C., Gautier, J.F., A comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with Type 2 diabetes inadequately controlled with metformin alone: a 52-week, randomized study. Diab Med 27 (2010), 318–326.
Forst, T., Uhlig-Laske, B., Ring, A., Graefe-Mody, U., Friedrich, C., Herbach, K., et al. Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes. Diab Med 27 (2010), 1409–1419.
Bergenstal, R.M., Wysham, C., Macconell, L., Malloy, J., Walsh, B., Yan, P., et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 376 (2010), 431–439.
Rigby, S.P., Handelsman, Y., Lai, Y.L., Abby, S.L., Tao, B., Jones, M.R., Effects of colesevelam, rosiglitazone, or sitagliptin on glycemic control and lipid profile in patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy. Endocr Pract 16 (2010), 53–63.
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. Diab Metab Res Rev 26 (2010), 540–549.
Goke, B., Gallwitz, B., Eriksson, J., Hellqvist, A., Gause-Nilsson, I., Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial. Int J Clin Pract 64 (2010), 1619–1631.
Pratley, R.E., Nauck, M., Bailey, T., Montanya, E., Cuddihy, R., Filetti, S., et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet 375 (2010), 1447–1456.
Filozof, C., Schwartz, S., Foley, J.E., Effect of vildagliptin as add-on therapy to a low-dose metformin. World J Diab 1 (2010), 19–26.
Taskinen, M.R., Rosenstock, J., Tamminen, I., Kubiak, R., Patel, S., Dugi, K.A., et al. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diab Obes Metab 13 (2011), 65–74.
Yang, W., Pan, C.Y., Tou, C., Zhao, J., Gause-Nilsson, I., Efficacy and safety of saxagliptin added to metformin in Asian patients with type 2 diabetes mellitus: a randomized controlled trial. Diab Res Clin Pract 94 (2011), 217–224.
Arechavaleta, R., Seck, T., Chen, Y., Krobot, K.J., O'Neill, E.A., Duran, L., et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial. Diab Obes Metab 13 (2011), 160–168.
Bergenstal, R.M., Forti, A., Chiasson, J.L., Woloschak, M., Boldrin, M., Balena, R., Efficacy and safety of taspoglutide versus sitagliptin for type 2 diabetes mellitus (T-emerge 4 trial). Diab Ther, 3, 2012, 13.
Pan, C., Xing, X., Han, P., Zheng, S., Ma, J., Liu, J., et al. Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus. Diab Obes Metab 14 (2012), 737–744.
Derosa, G., Ragonesi, P.D., Carbone, A., Fogari, E., Bianchi, L., Bonaventura, A., et al. Vildagliptin added to metformin on beta-cell function after a euglycemic hyperinsulinemic and hyperglycemic clamp in type 2 diabetes patients. Diab Technol Ther 14 (2012), 475–484.
Ross, S.A., Rafeiro, E., Meinicke, T., Toorawa, R., Weber-Born, S., Woerle, H.J., Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trial. Curr Med Res Opin 28 (2012), 1464–1475.
Gallwitz, B., Rosenstock, J., Rauch, T., Bhattacharya, S., Patel, S., von Eynatten, M., et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 380 (2012), 475–483.
Yang, W., Guan, Y., Shentu, Y., Li, Z., Johnson-Levonas, A.O., Engel, S.S., et al. The addition of sitagliptin to ongoing metformin therapy significantly improves glycemic control in Chinese patients with type 2 diabetes. J Diab 4 (2012), 227–237.
Seino, Y., Miyata, Y., Hiroi, S., Hirayama, M., Kaku, K., Efficacy and safety of alogliptin added to metformin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study. Diab Obes Metab 14 (2012), 927–936.
Aschner, P., Chan, J., Owens, D.R., Picard, S., Wang, E., Dain, M.P., et al. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial. Lancet 379 (2012), 2262–2269.
Hermans, M.P., Delibasi, T., Farmer, I., Lohm, L., Maheux, P., Piatti, P., et al. Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes: the PROMPT study. Curr Med Res Opin 28 (2012), 1635–1645.
Rhee, E.J., Lee, W.Y., Min, K.W., Shivane, V.K., Sosale, A.R., Jang, H.C., et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor gemigliptin compared with sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diab Obes Metab 15 (2013), 523–530.
Charbonnel, B., Steinberg, H., Eymard, E., Xu, L., Thakkar, P., Prabhu, V., et al. Efficacy and safety over 26 weeks of an oral treatment strategy including sitagliptin compared with an injectable treatment strategy with liraglutide in patients with type 2 diabetes mellitus inadequately controlled on metformin: a randomised clinical trial. Diabetologia 56 (2013), 1503–1511.
Odawara, M., Hamada, I., Suzuki, M., Efficacy and safety of vildagliptin as add-on to metformin in Japanese patients with type 2 diabetes mellitus. Diab Ther 5 (2014), 169–181.
Nauck, M., Weinstock, R.S., Umpierrez, G.E., Guerci, B., Skrivanek, Z., Milicevic, Z., Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diab Care 37 (2014), 2149–2158.
White, J.L., Buchanan, P., Li, J., Frederich, R., A randomized controlled trial of the efficacy and safety of twice-daily saxagliptin plus metformin combination therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy. BMC Endocr Disord, 14, 2014, 17.
Ludemann, J., Dutting, E.D., Dworak, M., Patient preference and tolerability of a DPP-4 inhibitor versus a GLP-1 analog in patients with type 2 diabetes mellitus inadequately controlled with metformin: a 24-week, randomized, multicenter, crossover study. Ther Adv Endocrinol Metab 6 (2015), 141–148.
Schernthaner, G., Duran-Garcia, S., Hanefeld, M., Langslet, G., Niskanen, L., Ostgren, C.J., et al. Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION). Diab Obes Metab 17 (2015), 630–638.
Kim, M.K., Rhee, E.J., Han, K.A., Woo, A.C., Lee, M.K., Ku, B.J., et al. Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled phase III trial. Diab Obes Metab 17 (2015), 309–312.
Wang, W., Yang, J., Yang, G., Gong, Y., Patel, S., Zhang, C., et al. Efficacy and safety of linagliptin in Asian patients with type 2 diabetes mellitus inadequately controlled by metformin: a multinational 24-week, randomized clinical trial. J Diab 8 (2016), 229–237.
Ji, L.N., Pan, C.Y., Lu, J.M., Li, H., Zhu, D.L., Li, Q., et al. Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin uptitration in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy: a randomized, open-label, prospective study (VISION). Diab Obes Metab 18 (2016), 775–782.
Kim, J.H., Kim, S.S., Baek, H.S., Lee, I.K., Chung, D.J., Sohn, H.S., et al. Comparison of vildagliptin and pioglitazone in Korean patients with type 2 diabetes inadequately controlled with metformin. Diab Metab J 40 (2016), 230–239.
Pan, C., Han, P., Ji, Q., Li, C., Lu, J., Yang, J., et al. Efficacy and safety of alogliptin in patients with type 2 diabetes mellitus: A multicentre randomized double-blind placebo-controlled Phase 3 study in mainland China, Taiwan, and Hong Kong. J Diab 9 (2017), 386–395.
Goldenberg, R., Gantz, I., Andryuk, P.J., O'Neill, E.A., Kaufman, K.D., Lai, E., 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. Diab Obes Metab 19 (2017), 394–400.
Hong, S.M., Park, C.Y., Hwang, D.M., Han, K.A., Lee, C.B., Chung, C.H., et al. Efficacy and safety of adding evogliptin versus sitagliptin for metformin-treated patients with type 2 diabetes: a 24-week randomized, controlled trial with open label extension. Diab Obes Metab 19 (2017), 654–663.
Gadde, K.M., Vetter, M.L., Iqbal, N., Hardy, E., Ohman, P., investigators, D-N-s., Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: the DURATION-NEO-2 randomized clinical study. Diab Obes Metab 19 (2017), 979–988.
Du, J., Liang, L., Fang, H., Xu, F., Li, W., Shen, L., et al. Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy: results of a Phase IV open-label randomized controlled study (the SMART study). Diab Obes Metab 19 (2017), 1513–1520.
Ajmani, A.K., Agrawal, A., Prasad, B.L.N., Basu, I., Shembalkar, J., Manikanth, N., et al. Efficacy and safety of evogliptin versus sitagliptin as an add-on therapy in Indian patients with type 2 diabetes mellitus inadequately controlled with metformin: a 24-week randomized, double-blind, non-inferiority, EVOLUTION INDIA study. Diab Res Clin Pract, 157, 2019, 107860.
Handelsman, Y., Mathieu, C., Del Prato, S., Johnsson, E., Kurlyandskaya, R., Iqbal, N., et al. Sustained 52-week efficacy and safety of triple therapy with dapagliflozin plus saxagliptin versus dual therapy with sitagliptin added to metformin in patients with uncontrolled type 2 diabetes. Diab Obes Metab, 2018, 10.1111/dom.13594 [Epub: Nov 30. Epub ahead of print].
Shyangdan, D.S., Uthman, O.A., Waugh, N., SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. BMJ open, 6, 2016, e009417.
Craddy, P., Palin, H.J., Johnson, K.I., Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diab Ther 5 (2014), 1–41.
Cai, X.L., Ji, L.N., Treatment response between Asian and non-Asian patients with type 2 diabetes: is there any similarity or difference?. Chin Med J (Engl) 132 (2019), 1–3.
Kim, Y.G., Hahn, S., Oh, T.J., Kwak, S.H., Park, K.S., Cho, Y.M., Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia 56 (2013), 696–708.
Cai, X., Han, X., Luo, Y., Ji, L., Efficacy of dipeptidyl-peptidase-4 inhibitors and impact on beta-cell function in Asian and Caucasian type 2 diabetes mellitus patients: a meta-analysis. J Diab 7 (2015), 347–359.
Cai, X., Gao, X., Yang, W., Chen, Y., Zhang, S., Zhou, L., et al. No disparity of the efficacy and all-cause mortality between Asian and non-Asian type 2 diabetes patients with sodium-glucose cotransporter 2 inhibitors treatment: a meta-analysis. J Diab Investig 9 (2018), 850–861.
Jones, A.G., Lonergan, M., Henley, W.E., Pearson, E.R., Hattersley, A.T., Shields, B.M., Should studies of diabetes treatment stratification correct for baseline HbA1c?. PLoS One, 11, 2016, e0152428.
Esposito, K., Chiodini, P., Capuano, A., Maiorino, M.I., Bellastella, G., Giugliano, D., Baseline glycemic parameters predict the hemoglobin A1c response to DPP-4 inhibitors: meta-regression analysis of 78 randomized controlled trials with 20,053 patients. Endocrine 46 (2014), 43–51.
Abe, T., Matsubayashi, Y., Yoshida, A., Suganami, H., Nojima, T., Osawa, T., et al. Predictors of the response of HbA1c and body weight after SGLT2 inhibition. Diab Metab 44 (2018), 172–174.
Demir, S., Temizkan, S., Sargin, M., C-peptide levels predict the effectiveness of dipeptidyl peptidase-4 inhibitor therapy. J Diab Res, 2016, 2016, 4509603.
Kim, S.A., Shim, W.H., Lee, E.H., Lee, Y.M., Beom, S.H., Kim, E.S., et al. Predictive clinical parameters for the therapeutic efficacy of sitagliptin in Korean type 2 diabetes mellitus. Diab Metab J 35 (2011), 159–165.
Lim, S., An, J.H., Shin, H., Khang, A.R., Lee, Y., Ahn, H.Y., et al. Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study. Clin Endocrinol (Oxf) 77 (2012), 215–223.
Monnier, L., Lapinski, H., Colette, C., Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diab Care 26 (2003), 881–885.
Inoue, H., Tamaki, Y., Kashihara, Y., Muraki, S., Kakara, M., Hirota, T., et al. Efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients: a model-based meta-analysis. Br J Clin Pharmacol 85 (2019), 393–402.
Zhang, Q., Dou, J., Lu, J., Combinational therapy with metformin and sodium-glucose cotransporter inhibitors in management of type 2 diabetes: systematic review and meta-analyses. Diab Res Clin Pract 105 (2014), 313–321.
Scheen, A.J., Effect of SGLT2 inhibitors on the sympathetic nervous system and blood pressure. Curr Cardiol Rep, 21, 2019, 70.
Bonnet, F., Scheen, A.J., Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: potential contribution for diabetic complications and cardiovascular disease. Diab Metab 44 (2018), 457–464.
Scheen, A.J., Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: a common comorbidity associated with severe complications. Diab Metab 45 (2019), 213–223.
Scheen, A.J., Why not adding a glucose-lowering agent with proven cardioprotection in high-risk patients with type 2 diabetes at HbA1c target on metformin?. Diab Res Clin Pract 147 (2019), 169–171.
Rehman, M.B., Tudrej, B.V., Soustre, J., Buisson, M., Archambault, P., Pouchain, D., et al. Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: meta-analysis of placebo-controlled randomized clinical trials. Diab Metab 43 (2017), 48–58.
Scheen, A.J., Effects of glucose-lowering agents on renal surrogate endpoints and hard clinical outcomes in patients with type 2 diabetes. Diab Metab 45 (2019), 110–121.
Bonnet, F., Scheen, A.J., Impact of glucose-lowering therapies on risk of stroke in type 2 diabetes. Diab Metab 43 (2017), 299–313.
Cosentino, F., Grant, P.J., Aboyans, V., Bailey, C.J., Ceriello, A., Delgado, V., et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 41 (2020), 255–323.
Scheen, A.J., Challenging 2019 ESC guidelines for the management of type 2 diabetes. Diab Metab, 2019, 10.1016/j.diabet.2019.10.006 [Epub ahead of print. pii: S1262-3636(19)30178-8].
Buse, J.B., Wexler, D.J., Tsapas, A., Rossing, P., Mingrone, G., Mathieu, C., 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 (2020), 221–228.
Scheen, A.J., The safety of gliptins: updated data in 2018. Expert Opin Drug Saf 17 (2018), 387–405.
Scheen, A.J., An update on the safety of SGLT2 inhibitors. Expert Opin Drug Safety 18 (2019), 295–311.