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Horm Metab Res 2018; 50(10): 768-777
DOI: 10.1055/a-0733-7919
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

SGLT-2 Inhibitors and DPP-4 Inhibitors as Second-Line Drugs in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials

Keke Wang
1   Department of Pharmacy, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
2   Department of the Pharmacy of China Medical University, Shenyang, Liaoning, China
,
Yansong Zhang
1   Department of Pharmacy, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
2   Department of the Pharmacy of China Medical University, Shenyang, Liaoning, China
,
Chunyang Zhao
1   Department of Pharmacy, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
2   Department of the Pharmacy of China Medical University, Shenyang, Liaoning, China
,
Mingyan Jiang
1   Department of Pharmacy, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
2   Department of the Pharmacy of China Medical University, Shenyang, Liaoning, China
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Publikationsverlauf

received 31. Mai 2018

accepted 04. September 2018

Publikationsdatum:
27. September 2018 (online)

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Abstract

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors are both novel and second-line therapies in type 2 diabetes mellitus, yet no well-rounded comparison of these two drugs has been published. Upon searching randomized controlled trials in databases from inception to July 2018, we collected studies on the efficacy or safety of SGLT-2 inhibitors compared with those of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. A total of 12 randomized controlled studies including 4342 patients were included in this meta-analysis. Compared with DPP-4 inhibitors, SGLT-2 inhibitors achieved greater reductions in HbA1c (SMD –0.22; 95% CI: –0.30, –0.14; p=0.000) and fasting plasma glucose (SMD –0.48; 95% CI: –0.56, –0.41; p=0.000). In addition, these reductions increased with a prolonged treatment duration from 12 to 78 weeks. Geographically, significant reductions of SGLT-2 inhibitors in HbA1c and FPG were found in North America and Europe, but not in Asia. Furthermore, SGLT-2 inhibitors showed greater reductions in body weight (SMD −0.72; 95% CI: –0.81, –0.63; p=0.000) from baseline, with an increased incidence of genital infections (OR 4.49; 95% CI: 2.96, 6.83; p=0.000) and pollakiuria (OR 2.24; 95% CI: 1.05, 4.79; p=0.037) and a decreased incidence of hypertension and hyperglycemia. Overall, the current meta-analysis demonstrated that compared to DPP-4 inhibitors, SGLT-2 inhibitors have beneficial effects on HbA1c, FPG, body weight, SBP, DBP, and HDL-cholesterol in patients with type 2 diabetes. However, SGLT-2 inhibitors are associated with increased total cholesterol and LDL-cholesterol and a higher incidence of genital infections and pollakiuria.

Key words

SGLT-2 inhibitors - DPP-4 inhibitors - type 2 diabetes mellitus - meta-analysis

Supplementary Material

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  • References

  • 1 Li Y, Qian H, Huang WL. SGLT-2 inhibitors: a new therapy for diabetes. Chin J New Drugs 2011; 20: 2073-2079
    PubMedSuche in Google Scholar
  • 2 Neumiller JJ, White Jr. JR, Campbell RK. Sodium-glucose co-transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 2010; 70: 377-385
    CrossrefPubMedSuche in Google Scholar
  • 3 Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JH, Kemper M, Volti SL, Neuhaus T, Skovby F, Swift PG, Schaub J, Klaerke D. Molecular analysis of the SGLT-2 gene in patients with renal glucosuria. J Am Soc Nephrol 2003; 14: 2873-2882
    CrossrefPubMedSuche in Google Scholar
  • 4 Kadowaki T, Haneda M, Inagaki N, Terauchi Y, Taniguchi A, Koiwai K, Rattunde H, Woerle HJ, Broedl UC. Efficacy and Safety of Empagliflozin Monotherapy for 52 Weeks in Japanese Patients with Type 2 Diabetes: A Randomized, Double-Blind, Parallel-Group Study. Adv Therap 2015; 32: 306-318
    CrossrefPubMedSuche in Google Scholar
  • 5 Bailey CJ, Morales Villegas EC, Woo V, Tang W, Ptaszynska A, List JF. Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: A randomized double-blind placebo-controlled 102-week trial. Diabetic Med 2015; 32: 531-541
    CrossrefPubMedSuche in Google Scholar
  • 6 Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Exp Opin Pharmacother 2013; 14: 2047-2058
    CrossrefPubMedSuche in Google Scholar
  • 7 Katzeff HL, Williamsherman D, Xu L, Golm GT, Wang H, Dong Q, Johnson JR, O'Neill EA, Kaufman KD, Engel SS, Goldstein BJ. Long-term efficacy of sitagliptin as either monotherapy or add-on therapy to metformin: improvement in glycemic control over 2 years in patients with type 2 diabetes. Curr Med Res Opin 2015; 31: 1071-1077
    CrossrefPubMedSuche in Google Scholar
  • 8 Wang LG, Wang H, Liu Q, Hua WC, Li CM. A network meta-analysis for efficacy and safety of seven regimens in the treatment of type II diabetes. Biomed Pharmacother 2017; 92: 707-719
    CrossrefPubMedSuche in Google Scholar
  • 9 Horie A, Tokuyama Y, Ishizuka T, Suzuki Y, Marumo K, Oshikiri K, Ide K, Sunaga M, Kanatsuka A. The dipeptidyl peptidase-4 inhibitor vildagliptin has the capacity to repair β-cell dysfunction andinsulin resistance. Horm Metab Res 2014; 46: 814-818
    Thieme ConnectPubMedSuche in Google Scholar
  • 10 Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-centered Approach. Diabetes Care 2015; 38: 140-149
    CrossrefPubMedSuche in Google Scholar
  • 11 Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, DeFronzo RA, Einhorn D, Fonseca VA, Garber JR, Garvey WT, Grunberger G, Handelsman Y, Henry RR, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez GE. Consensus statement by the American association of clinical endocrinologists and American college of endocrinology on the comprehensive type 2 diabetes management algorigthm-2016 executive summary. Endocr Pact 2016; 22: 84-112
    PubMedSuche in Google Scholar
  • 12 Tamez-Pérez HE, Proskauer-Peña SL, Hernŕndez-Coria MI, Garber AJ. AACE Comprehensive Diabetes Management Algorithm 2013. Endocr Pract 2013; 19: 736-737
    CrossrefPubMedSuche in Google Scholar
  • 13 American Diabetes Association . Standards Medical Care in Diabetes-2018. Diabetes Care 2018; 41: S1-S155
    CrossrefPubMedSuche in Google Scholar
  • 14 Mishriky BM, Tanenberg RJ, Sewell KA, Cummings DM. 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. Diabetes Metab 2018; 44: 112-120
    CrossrefPubMedSuche in Google Scholar
  • 15 Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N, Mason J, Middleton P, Mrukowicz J, O’Connell D, Oxman AD, Phillips B, Schünemann HJ, Edejer T, Varonen H, Vist GE, Williams Jr. JW, Zaza S. Grading quality of evidence and strength of recommendations. BMJ 2004; 328: 1490
    CrossrefPubMedSuche in Google Scholar
  • 16 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
    CrossrefPubMedSuche in Google Scholar
  • 17 Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: 889-893
    PubMedSuche in Google Scholar
  • 18 Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. Cochrane Database of Systematic Reviews 2011; 102-108
    PubMedSuche in Google Scholar
  • 19 Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: Is blinding necessary?. Control Clin Trials 1996; 17: 1-12
    CrossrefPubMedSuche in Google Scholar
  • 20 Roden M, Merker L, Christiansen AV, Roux F, Salsali A, Kim G, Stella P, Woerle HJ, Broedl UC. Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug-naïve patients with type 2 diabetes: A double-blind extension of a Phase III randomized controlled trial. Cardiovasc Diabetol 2015; 14: 1-11
    CrossrefPubMedSuche in Google Scholar
  • 21 Rosenstock J, Seman LJ, Jelaska A, Hantel S, Pinnetti S, Hach T, Woerle HJ. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab 2013; 15: 1154-1160
    CrossrefPubMedSuche in Google Scholar
  • 22 Lavalle-González FJ, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: A randomisedtrial. Diabetologia 2013; 56: 2582-2592
    CrossrefPubMedSuche in Google Scholar
  • 23 Rosenstock J, Aggarwal N, Polidori D, Zhao Y, Arbit D, Usiskin K, Capuano G, Canovatchel W. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 2012; 35: 1232-1238
    CrossrefPubMedSuche in Google Scholar
  • 24 Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, Kawaguchi M, Canovatchel W, Meininger G. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: A 52-week randomized trial. Diabetes Care 2013; 36: 2508-2515
    CrossrefPubMedSuche in Google Scholar
  • 25 Ferrannini E, Berk A, Hantel S, Pinnetti S, Hach T, Woerle HJ, Broedl UC. Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes. Diabetes Care 2013; 36: 4015-4021
    CrossrefPubMedSuche in Google Scholar
  • 26 DeFronzo RA, Lewin A, Patel S, Liu D, Kaste R, Woerle HJ, Broedl UC. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care 2015; 38: 276-282
    PubMedSuche in Google Scholar
  • 27 Lewin A, DeFronzo RA, Patel S, Liu D, Kaste R, Woerle HJ, Broedl UC. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care 2015; 38: 394-402
    CrossrefPubMedSuche in Google Scholar
  • 28 Roden M, Weng J, Eilbracht J, Delafont B, Kim G, Woerle HJ, Broedl UC. 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 2013; 1: 208-219
    CrossrefPubMedSuche in Google Scholar
  • 29 Rosenstock J, Hansen L, Zee P, Li Y, Cook W, Hirshberg B, Iqbal N. 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
    CrossrefPubMedSuche in Google Scholar
  • 30 Hayashi T, Fukui T, Nakanishi N, Yamamoto S, Tomoyasu M, Osamura A, Ohara M, Yamamoto T, Ito Y, Hirano T. Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: Comparison with sitagliptin. Cardiovasc Diabetol 2017; 16: 8
    CrossrefPubMedSuche in Google Scholar
  • 31 Pratley RE, Eldor R, Raji A, Golm G, Huyck SB, Qiu Y, Sunga S, Johnson J, Terra SG, Mancuso JP, Engel SS, Lauring B. 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. Diabetes Obes Metab 2018; 20: 1111-1120
    CrossrefPubMedSuche in Google Scholar
  • 32 Zhong X, Lai D, Ye Y, Yang X, Yu B, Huang Y. Efficacy and safety of empagliflozin as add-on to metformin for type 2 diabetes: A systematic review and meta-analysis. Eur J Clin Pharmacol 2016; 72: 655-663
    CrossrefPubMedSuche in Google Scholar
  • 33 Monami M, Liistro F, Scatena A, Nreu B, Mannucci E. Short and medium-term efficacy of sodium glucose co-transporter-2 (SGLT-2) inhibitors: A meta-analysis of randomized clinical trials. Diabetes Obes Metab 2018; 20: 1213-1222
    CrossrefPubMedSuche in Google Scholar
  • 34 Weber MA, Mansfield TA, Cain VA, Iqbal N, Parikh S, Ptaszynska A. Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: A randomised, double-blind, placebo-controlled, phase 3 study. Lancet Diabetes Endocrinol 2016; 4: 211-220
    CrossrefPubMedSuche in Google Scholar
  • 35 Yang XP, Lai D, Zhong XY, Shen HP, Huang YL. Efficacy and safety of canagliflozin in subjects with type 2 diabetes: Systematic review and meta-analysis. Eur J Clin Pharmacol 2014; 70: 1149-1158
    CrossrefPubMedSuche in Google Scholar
  • 36 Min SH, Yoon JH, Hahn S, Cho YM. Comparison between SGLT-2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: A systematic review with indirect comparison meta-analysis. Diabetes Metab Res Rev 2017; 33: 1-11
    PubMedSuche in Google Scholar
  • 37 Molugulu N, Yee LS, Ye YT, Khee TC, Nie LZ, Yee NJ, Yee TK, Liang TC, Kesharwani P. Systematic review of metformin monotherapy and dual therapy with sodium glucose co-transporter 2 inhibitor (SGLT-2) in treatment of type 2 diabetes mellitus. Diabetes Res Clin Pract 2017; 132: 157-168
    CrossrefPubMedSuche in Google Scholar
  • 38 Devenny JJ, Godonis HE, Harvey SJ, Rooney S, Cullen MJ, Pelleymounter MA. Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesity (Silver Spring) 2012; 20: 1645-1652
    CrossrefPubMedSuche in Google Scholar
  • 39 Bailey CJ. Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci 2011; 32: 63-71
    CrossrefPubMedSuche in Google Scholar
  • 40 Ferrannini E, Solini A. SGLT-2 inhibition in diabetes mellitus: Rationale and clinical prospects. Nat Rev Endocrinol 2012; 8: 495-502
    CrossrefPubMedSuche in Google Scholar
  • 41 Kawalec P, Mikrut A, Lopuch S. The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab Res Rev 2014; 30: 269-283
    CrossrefPubMedSuche in Google Scholar
  • 42 Puckrin R, Saltiel MP, Reynier P, Azoulay L, Yu OHY, Filion KB. SGLT-2 inhibitors and the risk of infections: A systematic review and meta-analysis of randomized controlled trials. Acta Diabetol 2018; 55: 503-514
    CrossrefPubMedSuche in Google Scholar
  • 43 Scheen AJ, Paquot N. Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence. Diabetes & Metabolism 2014; 40: S4-S11
    CrossrefPubMedSuche in Google Scholar
  • 44 Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with type 2 diabetes. Diabetologia 2014; 57: 891-901
    CrossrefPubMedSuche in Google Scholar
  • 45 Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2016; 101: 157-166
    CrossrefPubMedSuche in Google Scholar