Dapagliflozin efficacy as an add-on therapy in double and triple-drug regimens: A meta-analysis of randomized control trial
A meta-analysis of randomized control trial
Abstract
Background: Diabetes is one of the most common diseases compared to others. There are many drugs available in the market to treat diabetes. Still, most of them have adverse drug reactions like hypoglycemia, weight gain, and subtherapeutic drug concentrations. SGLT-2 inhibitors are a new class of drugs used as add-on therapy to treat type-2 Diabetes Mellitus. They act by inhibiting glucose reabsorption and increasing glucose excretion via the kidneys. In an average adult, two kidneys filter about 180g of glucose per day. About 98% of the glucose filtered in the kidneys get reabsorbed in the proximal convoluted tubule back into the bloodstream, which can be inhibited by SGLT-2 inhibitors.
Method: A systematic review and meta-analysis were performed on randomized clinical trial data, extracted from PubMed, Cochrane and Embase. All data, including baseline and shift of baseline, standard deviation, and number of participants, were recorded for HbA1c, Fasting blood glucose (FBG), Bodyweight and SBP/DBP.
Results: Twelve randomized clinical trials, including 8000 participants, were compared and divided into three groups of drugs: SAXA+DAPA+MET, SAXA+MET and DAPA+MET. The comparison is done for HbA1c (WMD:-6.78; 95% CI:-8.28; P <0.00001) (WMD:-4.88; 95% CI:-6.93; P <0.00001), FBG (SMD: -6.50; 95% CI: -8.55, -4.45; P <0.00001) (SMD: -7.75; 95% CI: -8.84, -6.66; P<0.00005,), body weight (SMD: 0.30; 95% CI: 0.27, 0.33; P =1.00) (SMD: -1.00; 95% CI: -1.90, -0.10; P<0.00001). Conclusion: Dapagliflozin, when given in combination, shows a major improvement in HbA1c and FBG levels and does not affect body weight. It was shown to be more effective when given in triple combination therapy.
Keywords: Dapagliflozine, meta-analysis, Sexagliptine, Metformin, Type two diabetes mellitus (T2DM), Sodium-glucose Cotransporter-2 (SGLT2)
Downloads
References
2. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet [Internet]. 2014; 53(1):17–27. Available from: http://dx.doi.org/10.1007/s40262-013-0104-3
3. Yang L, Li H, Li H, Bui A, Chang M, Liu X, et al. Pharmacokinetic and pharmacodynamic properties of single- and multiple-dose of dapagliflozin, a selective inhibitor of SGLT2, in healthy Chinese subjects. Clin Ther [Internet]. 2013; 35(8):1211-1222.e2. Available from: http://dx.doi.org/10.1016/j.clinthera.2013.06.017
4. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab [Internet]. 2011; 13(4):357–65. Available from: http://dx.doi.org/10.1111/j.1463-1326.2011.01359.x
5. Anderson SL. Dapagliflozin efficacy and safety: a perspective review. Ther Adv Drug Saf [Internet]. 2014; 5(6):242–54. Available from: http://dx.doi.org/10.1177/2042098614551938
6. Matthaei S, Catrinoiu D, Celiński 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 [Internet]. 2015; 38(11):2018–24. Available from: http://dx.doi.org/10.2337/dc15-0811
7. Matthaei S, Aggarwal N, Garcia-Hernandez P, Iqbal N, Chen H, Johnsson E, et al. One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin. Diabetes Obes Metab [Internet]. 2016; 18(11):1128–33. Available from: http://dx.doi.org/10.1111/dom.12741
8. Mathieu C, Ranetti AE, 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 [Internet]. 2015; 38(11):2009–17. Available from: http://dx.doi.org/10.2337/dc15-0779
9. Mathieu C, Herrera Marmolejo M, González González JG, Hansen L, Chen H, Johnsson E, et al. Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes. Diabetes Obes Metab [Internet]. 2016;18(11):1134–7. Available from: http://dx.doi.org/10.1111/dom.1273
10. Del Prato S, Rosenstock J, Garcia-Sanchez R, Iqbal N, Hansen L, Johnsson E, et al. Safety and tolerability of dapagliflozin, saxagliptin and metformin in combination: Post-hoc analysis of concomitant add-on versus sequential add-on to metformin and of triple versus dual therapy with metformin. Diabetes Obes Metab [Internet]. 2018; 20(6):1542–6. Available from: http://dx.doi.org/10.1111/dom.13258
11. 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 [Internet]. 2015; 38(3):376–83. Available from: http://dx.doi.org/10.2337/dc14-1142
12. Rosenstock J, Perl S, Johnsson E, García-Sánchez R, Jacob S. Triple therapy with low-dose dapagliflozin plus saxagliptin versus dual therapy with each monocomponent, all added to metformin, in uncontrolled type 2 diabetes. Diabetes Obes Metab [Internet]. 2019 [cited 2022 Nov 4]; 21(9):2152–62. Available from: https://www.semanticscholar.org/paper/6813d945d44bdbb83119c5958fd19feed6bd2a14
13. Müller-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. Diabetes Obes Metab [Internet]. 2018; 20(11):2598–607. Available from: http://dx.doi.org/10.1111/dom.13437
14. 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 [Internet]. 2017; 19(3):348–55. Available from: http://dx.doi.org/10.1111/dom.12825
15. Müller-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. Diabetes Obes Metab [Internet]. 2018; 20(11):2598–607. Available from: http://dx.doi.org/10.1111/dom.13437
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
.