Clinical Efficacy of Different Doses of Canagliflozin Combined with Metformin in the Treatment of Type 2 Diabetes Mellitus: a Meta-analysis

doi:10.12114/j.issn.1007-9572.2022.0073

Chinese General Practice ›› 2022, Vol. 25 ›› Issue (15): 1888-1896,1905.DOI: 10.12114/j.issn.1007-9572.2022.0073

Special Issue: 内分泌代谢性疾病最新文章合辑

• Evidence-based Medicine • Previous Articles Next Articles

Clinical Efficacy of Different Doses of Canagliflozin Combined with Metformin in the Treatment of Type 2 Diabetes Mellitus: a Meta-analysis

1. NHC Key Laboratory of Hormones and Development/Tianjin Key Laboratory of Metabolic Diseases/Tianjin Institute of Endocrinology, Tianjin 300134, China
2. Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin 300134, China

Received:2022-01-19 Revised:2022-02-26 Published:2022-03-17 Online:2022-04-07
Contact: Daiqing LI
About author:
CHEN Y Y, LI X D, TANG Y Z, et al. Clinical efficacy of different doses of canagliflozin combined with metformin in the treatment of type 2 diabetes mellitus: a meta-analysis[J]. Chinese General Practice, 2022, 25 (15) : 1888-1896, 1905.

不同剂量卡格列净联合二甲双胍治疗2型糖尿病临床疗效的Meta分析

1. 300134　天津市，国家卫生健康委员会激素与发育重点实验室　天津市代谢性疾病重点实验室　天津市内分泌研究所
2. 300134　天津市，天津医科大学朱宪彝纪念医院

通讯作者: 李代清
作者简介:
陈玉英，李晓冬，汤云昭，等.不同剂量卡格列净联合二甲双胍治疗2型糖尿病临床疗效的Meta分析[J].中国全科医学，2022，25（15）：1888-1896，1905. [www.chinagp.net] 作者贡献：陈玉英负责提出研究思路和方案；陈玉英、李晓东负责检索文献、收集文献、绘制森林图及结果解读；陈玉英负责论文撰写和修订；汤云昭、李代清负责文章质量控制和审校，对整体文章负责，监督管理；所有作者确认了论文的最终稿。
基金资助:
国家自然科学基金青年基金资助项目(81600628/H0713); 天津市自然科学基金资助项目(16JCYBJC25700)

Abstract

Abstract:

Background

Canagliflozin (CANA) and metformin (MET) can both be used in the treatment of type 2 diabetes (T2DM) , but the clinical efficacy of combined use remains to be further clarified.

Objective

To elevate the efficacy and safety of CANA combined with MET in the treatment of T2DM, and to provide clinical reference for the treatment of T2DM.

Methods

A systematic review of published randomized controlled trials (RCTs) of 100 mg and/or 300 mg CANA combined with MET for T2DM performed in PubMed, Cochrane Library, EMBase, Clinical Trials.gov, CNKI Database, VIP Database, Wanfang Databases from inception to 18 April 2021 were retrieved by computer, and the included references were retrieved manually. After literature screening, data extraction and quality evaluation, meta-analysis was performed using RevMan 5.3 software.

Results

A total of 9 RCTs with 6 224 patients were included. Meta-analysis results showed that the levels of glycosylated hemoglobin (HbA_1c) , fasting blood glucose (FPG) , body weight, systolic blood pressure (SBP) , diastolic blood pressure (DBP) , and triacylglycerol (TG) in the 100 mg CANA combined with MET group and the 300 mg CANA combined with MET group were lower than placebo control group (P<0.05) . The levels of pancreatic β-cell function index (HOMA-β) , low-density lipoprotein cholesterol (LDL-C) , and high-density lipoprotein cholesterol (HDL-C) in the 100 mg CANA combined with MET group were higher than those in the placebo control group (P<0.05) . The levels of HbA_1c and SBP in the 300 mg CANA combined with MET group were lower than those in the active control group, and the level of HOMA-β was higher than that in the active control group (P<0.05) . The FPG, body weight, DBP and TG in the 100 mg CANA combined with MET group and 300 mg CANA combined with MET group were lower than those in the active control group, and the levels of LDL-C and HDL-C were higher than those in the active control group (P<0.05) . The incidence of reproductive system infection (female) in the 100 mg CANA combined with MET group was higher than that in the placebo control group (P<0.05) . The incidence of reproductive system infection (female) and osmotic diuresis-related adverse events in the 300 mg CANA combined with MET group was higher than that in the placebo control group (P<0.05) . The incidence of reproductive system infection (male) , reproductive system infection (female) , and osmotic diuresis in the 100 mg CANA combined with MET group and 300 mg CANA combined with MET group was higher than that in the active control group (P<0.05) .

Conclusion

100 mg and 300 mg of CANA combined with MET can effectively reduce HbA_1c and FPG levels, body weight, blood pressure and TG levels, and increase LDL-C and HDL-C levels in T2DM patients. For patients with T2DM poorly controlled by MET, it may be considered in combination with CANA, but attention should be paid to infection of the reproductive system. Therefore, high-quality large-sample trials are still needed to confirm the long-term safety of different doses of CANA combined with MET.

Key words: Diabetes mellitus, type 2, Canagliflozin, Metformin, Treatment outcome, Meta-analysis

摘要：

背景

卡格列净（CANA）和二甲双胍（MET）均可用于治疗2型糖尿病（T2DM），但联合使用的临床疗效有待进一步明确。

目的

评价CANA联合MET治疗T2DM的疗效和安全性，为T2DM的治疗提供临床参考。

方法

计算机检索PubMed、Cochrane Library、EMBase、Clinical Trails.gov、中国知网、维普网、万方数据知识服务平台，检索有关100 mg和/或300 mg的CANA联合MET治疗T2DM的随机对照试验（RCTs）（CANA联合MET组给予CANA联合MET，安慰剂对照组给予单用MET或者安慰剂联合MET/活性对照组给予其他口服降糖药物联合MET），检索时间为建库至2021-04-18，同时手工检索纳入文献的参考文献。经文献筛选、提取数据和质量评价后，采用RevMan 5.3软件进行Meta分析。

结果

共纳入9篇RCTs，6 224例患者。Meta分析结果显示，100 mg CANA联合MET组和300 mg CANA联合MET组糖化血红蛋白（HbA_1c）、空腹血糖（FPG）、体质量、收缩压（SBP）、舒张压（DBP）、三酰甘油（TG）水平均低于安慰剂对照组（P<0.05），胰岛β细胞功能指数（HOMA-β）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平高于安慰剂对照组（P<0.05）。300 mg CANA联合MET组HbA_1c、SBP均低于活性对照组，HOMA-β水平高于活性对照组（P<0.05）。100 mg CANA联合MET组和300 mg CANA联合MET组FPG、体质量、DBP、TG均低于活性对照组，LDL-C、HDL-C水平均高于活性对照组（P<0.05）。100 mg CANA联合MET组生殖系统感染（女性）发生率高于安慰剂对照组（P<0.05）；300 mg CANA联合MET组生殖系统感染（女性）、渗透利尿相关不良事件发生率均高于安慰剂对照组（P<0.05）；100 mg CANA联合MET组和300 mg CANA联合MET组生殖系统感染（男性）、生殖系统感染（女性）、渗透利尿相关不良事件发生率均高于活性对照组（P<0.05）。

结论

100 mg和300 mg CANA联合MET能有效降低T2DM患者HbA_1c、FPG，减轻体质量，降低血压和TG水平，提高LDL-C、HDL-C水平。对于MET控制不佳的T2DM患者，可考虑与CANA联合使用，但要注意生殖系统的感染。后期仍需要高质量的大样本试验，以确认不同剂量的CANA联合MET的长期安全性。

关键词: 糖尿病，2型, 坎格列嗪, 二甲双胍, 治疗结果, Meta分析

Yuying CHEN,Xiaodong LI,Yunzhao TANG, et al. Clinical Efficacy of Different Doses of Canagliflozin Combined with Metformin in the Treatment of Type 2 Diabetes Mellitus: a Meta-analysis[J]. Chinese General Practice, 2022, 25(15): 1888-1896,1905. DOI: 10.12114/j.issn.1007-9572.2022.0073.
陈玉英,李晓冬,汤云昭等. 不同剂量卡格列净联合二甲双胍治疗2型糖尿病临床疗效的Meta分析[J]. 中国全科医学, 2022, 25(15): 1888-1896,1905. DOI: 10.12114/j.issn.1007-9572.2022.0073.

Figures/Tables 23

References 33

[1]	GLOVACI D, FAN W J, WONG N D. Epidemiology of diabetes mellitus and cardiovascular disease[J]. Curr Cardiol Rep，2019，21（4）：21. DOI：10.1007/s11886-019-1107-y.
[2]	KAUSHAL S, SINGH H, THANGARAJU P，et al. Canagliflozin：a novel SGLT2 inhibitor for type 2 diabetes mellitus[J]. N Am J Med Sci，2014，6（3）：107-113. DOI：10.4103/1947-2714.128471.
[3]	ELKINSON S, SCOTT L J. Canagliflozin：first global approval[J]. Drugs，2013，73（9）：979-988. DOI：10.1007/s40265-013-0064-9.
[4]	LAMOS E M, YOUNK L M, DAVIS S N. Canagliflozin，an inhibitor of sodium-glucose cotransporter 2，for the treatment of type 2 diabetes mellitus[J]. Expert Opin Drug Metab Toxicol，2013，9（6）：763-775. DOI：10.1517/17425255.2013.791282.
[5]	ZILOV A V, ABDELAZIZ S I, ALSHAMMARY A，et al. Mechanisms of action of metformin with special reference to cardiovascular protection[J]. Diabetes Metab Res Rev，2019，35（7）：e3173. DOI：10.1002/dmrr.3173.
[6]	Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus[J]. Diabetes Care，2003，26（Suppl 1）：S5-20. DOI：10.2337/diacare.26.2007.s5.
[7]	HIGGINS J P T, ALTMAN D G, GØTZSCHE P C，et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials[J]. BMJ，2011，343：d5928. DOI：10.1136/bmj.d5928.
[8]	WILDING J P, CHARPENTIER G, HOLLANDER P，et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea：a randomised trial[J]. Int J Clin Pract，2013，67（12）：1267-1282. DOI：10.1111/ijcp.12322.
[9]	SCHERNTHANER G, GROSS J L, ROSENSTOCK J，et al. 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[J]. Diabetes Care，2013，36（9）：2508-2515. DOI：10.2337/dc12-2491.
[10]	ROSENSTOCK J, CHUCK L, GONZÁLEZ-ORTIZ M，et al. Initial combination therapy with canagliflozin plus metformin versus each component as monotherapy for drug-naïve type 2 diabetes[J]. Diabetes Care，2016，39（3）：353-362. DOI：10.2337/dc15-1736.
[11]	ROSENSTOCK J, AGGARWAL N, POLIDORI D，et al. Dose-ranging effects of canagliflozin，a sodium-glucose cotransporter 2 inhibitor，as add-on to metformin in subjects with type 2 diabetes[J]. Diabetes Care，2012，35（6）：1232-1238. DOI：10.2337/dc11-1926.
[12]	QIU R, CAPUANO G, MEININGER G. Efficacy and safety of twice-daily treatment with canagliflozin，a sodium glucose co-transporter 2 inhibitor，added on to metformin monotherapy in patients with type 2 diabetes mellitus[J]. J Clin Transl Endocrinol，2014，1（2）：54-60. DOI：10.1016/j.jcte.2014.04.001.
[13]	CEFALU W T, LEITER L A, YOON K H，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[J]. Lancet，2013，382（9896）：941-950. DOI：10.1016/S0140-6736(13)60683-2.
[14]	LAVALLE-GONZÁLEZ F J, JANUSZEWICZ A, DAVIDSON J，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[J]. Diabetologia，2013，56（12）：2582-2592. DOI：10.1007/s00125-013-3039-1.
[15]	JI L, HAN P, LIU Y，et al. Canagliflozin in Asian patients with type 2 diabetes on metformin alone or metformin in combination with sulphonylurea[J]. Diabetes Obes Metab，2015，17（1）：23-31. DOI：10.1111/dom.12385.
[16]	FORST T, GUTHRIE R, GOLDENBERG R，et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone[J]. Diabetes Obes Metab，2014，16（5）：467-477. DOI：10.1111/dom.12273.
[17]	YANG T, LU M, MA L Y，et al. Efficacy and tolerability of canagliflozin as add-on to metformin in the treatment of type 2 diabetes mellitus：a meta-analysis[J]. Eur J Clin Pharmacol，2015，71（11）：1325-1332. DOI：10.1007/s00228-015-1923-y.
[18]	GONZALEZ D E, FORESTO R D, RIBEIRO A B. SGLT-2 inhibitors in diabetes：a focus on renoprotection[J]. Rev Assoc Med Bras （1992），2020，66 Suppl（Suppl 1）：s17-24. DOI：10.1590/1806-9282.66.S1.17.
[19]	HUMMEL C S, LU C, LOO D D，et al. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2[J]. Am J Physiol Cell Physiol，2011，300（1）：C14-21. DOI：10.1152/ajpcell.00388.2010.
[20]	FERRANNINI E, MUSCELLI E, FRASCERRA S，et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients[J]. J Clin Invest，2014，124（2）：499-508. DOI：10.1172/JCI72227.
[21]	MARTINEZ R, AL-JOBORI H, ALI A M，et al. Endogenous glucose production and hormonal changes in response to canagliflozin and liraglutide combination therapy[J]. Diabetes，2018，67（6）：1182-1189. DOI：10.2337/db17-1278.
[22]	NESCHEN S, SCHEERER M, SEELIG A，et al. Metformin supports the antidiabetic effect of a sodium glucose cotransporter 2 inhibitor by suppressing endogenous glucose production in diabetic mice[J]. Diabetes，2015，64（1）：284-290. DOI：10.2337/db14-0393.
[23]	ROSENTHAL N, MEININGER G, WAYS K，et al. Canagliflozin：a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus[J]. Ann N Y Acad Sci，2015，1358：28-43. DOI：10.1111/nyas.12852.
[24]	TAKASHIMA H, YOSHIDA Y, NAGURA C，et al. Renoprotective effects of canagliflozin，a sodium glucose cotransporter 2 inhibitor，in type 2 diabetes patients with chronic kidney disease：a randomized open-label prospective trial[J]. Diab Vasc Dis Res，2018，15（5）：469-472. DOI：10.1177/1479164118782872.
[25]	MAZIDI M, REZAIE P, GAO H K，et al. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus：a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients[J]. J Am Heart Assoc，2017，6（6）：e004007. DOI：10.1161/JAHA.116.004007.
[26]	CEFALU W T, STENLÖF K, LEITER L A，et al. Effects of canagliflozin on body weight and relationship to HbA_1c and blood pressure changes in patients with type 2 diabetes[J]. Diabetologia，2015，58（6）：1183-1187. DOI：10.1007/s00125-015-3547-2.
[27]	BASU D, HUGGINS L A, SCERBO D，et al. Mechanism of increased LDL（low-density lipoprotein） and decreased triglycerides with SGLT2 （sodium-glucose cotransporter 2） inhibition[J]. Arterioscler Thromb Vasc Biol，2018，38（9）：2207-2216. DOI：10.1161/ATVBAHA.118.311339.
[28]	KATSIKI N, MIKHAILIDIS D P, THEODORAKIS M J. Sodium-glucose cotransporter 2 inhibitors （SGLT2i）：their role in cardiometabolic risk management[J]. Curr Pharm Des，2017，23（10）：1522-1532. DOI：10.2174/1381612823666170113152742.
[29]	KLUGER A Y, TECSON K M, LEE A Y，et al. Class effects of SGLT2 inhibitors on cardiorenal outcomes[J]. Cardiovasc Diabetol，2019，18（1）：99. DOI：10.1186/s12933-019-0903-4.
[30]	PERKOVIC V, DE ZEEUW D, MAHAFFEY K W，et al. Canagliflozin and renal outcomes in type 2 diabetes：results from the CANVAS Program randomised clinical trials[J]. Lancet Diabetes Endocrinol，2018，6（9）：691-704. DOI：10.1016/S2213-8587(18)30141-4.
[31]	TENTOLOURIS A, VLACHAKIS P, TZERAVINI E，et al. SGLT2 inhibitors：a review of their antidiabetic and cardioprotective effects[J]. Int J Environ Res Public Health，2019，16（16）：2965. DOI：10.3390/ijerph16162965.
[32]	DAVE C V, SCHNEEWEISS S, PATORNO E. Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors[J]. Diabetes Obes Metab，2019，21（2）：434-438. DOI：10.1111/dom.13531.
[33]	ZHU Y X, LI T, FAN S R，et al. Health-related quality of life as measured with the Short-Form 36（SF-36） questionnaire in patients with recurrent vulvovaginal candidiasis[J]. Health Qual Life Outcomes，2016，14：65. DOI：10.1186/s12955-016-0470-2.

第一作者	发表时间（年）	ID	干预措施	样本量（例）	年龄（岁）	T2DM病程（年）	疗程（周）	结局指标
WILDING^[8]	2013	NCT01106625	CANA 100 mg联合MET	157	57.4±10.5	9.0±5.7	26	①②③④⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	156	56.1±8.9	9.4±6.4
			PBO联合MET	156	56.8±8.3	10.3±6.7
SCHERNTHANER^[9]	2013	NCT01137812	CANA 300 mg联合MET	377	56.6±9.6	9.4±6.1	52	①②③④⑤⑥⑦⑧⑨
			SITA 100 mg联合MET	378	56.7±9.3	9.7±6.3
ROSENSTOCK^[10]	2016	NCT01809327	CANA 100 mg联合MET	237	54.2±9.6	2.9±3.3	26	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	237	55.4±9.8	3.3±3.9
			MET	237	55.2±9.8	3.3±4.5
ROSENSTOCK^[11]	2012	NCT00642278	CANA 100 mg联合MET	64	51.7±8.0	6.1±4.7	12	①②③④⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	64	52.3±6.9	5.9±5.2
			SITA 100 mg联合MET	65	51.7±8.1	5.6±4.7
			PBO联合MET	65	53.3±7.8	6.4±5.0
QIU^[12]	2014	NCT01340664	CANA 100 mg联合MET	93	58.6±8.9	6.7±4.9	18	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	93	56.7±10.3	7.3±6.0
			PBO联合MET	93	57.0±9.3	7.0±6.4
CEFALU^[13]	2013	NCT00968812	CANA 100 mg联合MET	483	56.4±9.5	6.5±5.5	52	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	485	55.8±9.2	6.7±5.5
			GIMA联合MET	482	56.3±9.0	6.6±5.0
LAVALLE-GONZÁLEZ^[14]	2013	NCT01106677	CANA 100 mg联合MET	368	55.5±9.4	6.7±5.4	26	①②③⑤⑥⑦⑧⑨
			CANA 300 mg联合MET	367	55.3±9.2	7.1±5.4
			SITA 100 mg联合MET	366	55.5±9.6	6.8±5.2
			PBO联合MET	183	55.3±9.8	6.8±5.3
JI^[15]	2015	NCT01381900	CANA 100 mg联合MET	223	56.5±8.3	6.8±4.5	18	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	227	56.4±9.2	6.9±4.9
			PBO联合MET	226	55.8±9.4	6.4±4.6
FORST^[16]	2014	NCT01106690	CANA 100 mg联合MET	113	56.7±10.4	10.5±6.6	26	①②③④⑤⑥⑦⑧⑨
			CANA 300 mg联合MET	114	57.0±10.2	11.0±7.6
			PBO联合MET	115	58.3±9.6	10.1±6.6

第一作者	发表时间（年）	ID	干预措施	样本量（例）	年龄（岁）	T2DM病程（年）	疗程（周）	结局指标
WILDING^[8]	2013	NCT01106625	CANA 100 mg联合MET	157	57.4±10.5	9.0±5.7	26	①②③④⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	156	56.1±8.9	9.4±6.4
			PBO联合MET	156	56.8±8.3	10.3±6.7
SCHERNTHANER^[9]	2013	NCT01137812	CANA 300 mg联合MET	377	56.6±9.6	9.4±6.1	52	①②③④⑤⑥⑦⑧⑨
			SITA 100 mg联合MET	378	56.7±9.3	9.7±6.3
ROSENSTOCK^[10]	2016	NCT01809327	CANA 100 mg联合MET	237	54.2±9.6	2.9±3.3	26	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	237	55.4±9.8	3.3±3.9
			MET	237	55.2±9.8	3.3±4.5
ROSENSTOCK^[11]	2012	NCT00642278	CANA 100 mg联合MET	64	51.7±8.0	6.1±4.7	12	①②③④⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	64	52.3±6.9	5.9±5.2
			SITA 100 mg联合MET	65	51.7±8.1	5.6±4.7
			PBO联合MET	65	53.3±7.8	6.4±5.0
QIU^[12]	2014	NCT01340664	CANA 100 mg联合MET	93	58.6±8.9	6.7±4.9	18	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	93	56.7±10.3	7.3±6.0
			PBO联合MET	93	57.0±9.3	7.0±6.4
CEFALU^[13]	2013	NCT00968812	CANA 100 mg联合MET	483	56.4±9.5	6.5±5.5	52	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	485	55.8±9.2	6.7±5.5
			GIMA联合MET	482	56.3±9.0	6.6±5.0
LAVALLE-GONZÁLEZ^[14]	2013	NCT01106677	CANA 100 mg联合MET	368	55.5±9.4	6.7±5.4	26	①②③⑤⑥⑦⑧⑨
			CANA 300 mg联合MET	367	55.3±9.2	7.1±5.4
			SITA 100 mg联合MET	366	55.5±9.6	6.8±5.2
			PBO联合MET	183	55.3±9.8	6.8±5.3
JI^[15]	2015	NCT01381900	CANA 100 mg联合MET	223	56.5±8.3	6.8±4.5	18	①②③⑤⑥⑦⑧⑨⑩
			CANA 300 mg联合MET	227	56.4±9.2	6.9±4.9
			PBO联合MET	226	55.8±9.4	6.4±4.6
FORST^[16]	2014	NCT01106690	CANA 100 mg联合MET	113	56.7±10.4	10.5±6.6	26	①②③④⑤⑥⑦⑧⑨
			CANA 300 mg联合MET	114	57.0±10.2	11.0±7.6
			PBO联合MET	115	58.3±9.6	10.1±6.6

结局	干预措施	CANA 100 mg联合MET				CANA 300 mg联合MET
结局	干预措施	文献数量（篇）	I²值（%）	OR（95%CI）	P值	文献数量（篇）	I²值（%）	OR（95%CI）	P值
总不良事件	PBO对照	5^{[8，10,11,12，15]}	0	1.00（0.81，1.23）	1.00	5^{[8，10,11,12，15]}	0	1.15（0.94，1.42）	0.17
	活性对照	2^[11，13]	66	0.91（0.71，1.16）	0.44	3^{[9，11，13]}	0	1.0（0.82，1.23）	1.00
严重不良事件	PBO对照	5^{[8，10,11,12，15]}	0	0.77（0.43，1.38）	0.37	5^{[8，10,11,12，15]}	0	0.76（0.42，1.38）	0.37
	活性对照	2^[11，13]	0	0.63（0.37，1.05）	0.07	3^{[9，11，13]}	27	0.84（0.57，1.23）	0.37
尿路感染	PBO对照	5^{[8，10,11,12，15]}	0	0.90（0.54，1.51）	0.70	5^{[8，10,11,12，15]}	9	1.00（0.61，1.65）	1.00
	活性对照	2^[11，13]	0	1.46（0.85，2.53）	0.17	3^{[9，11，13]}	27	1.09（0.72，1.66）	0.68
生殖系统感染（男性）	PBO对照	4^{[8，10，12，15]}	0	3.37（0.92，12.32）	0.07	4^{[8，10，12，15]}	0	2.74（0.80，9.36）	0.11
	活性对照	1^[13]	-	5.82（1.70，20.01）	0.005	2^[9，13]	0	10.12（3.60，28.42）	<0.000 1
生殖系统感染（女性）	PBO对照	4^{[8，10，12，15]}	0	3.13（1.42，6.88）	0.005	4^{[8，10，12，15]}	0	2.73（1.23，6.06）	0.01
	活性对照	1^[13]	-	5.43（2.07，14.26）	0.000 6	2^[9，13]	0	5.29（2.82，9.91）	<0.000 01
渗透利尿相关不良事件	PBO对照	4^{[8，10，12，15]}	4	1.64（0.67，4.00）	0.27	4^{[8，10，12，15]}	30	3.20（1.47，6.97）	0.003
	活性对照	1^[13]	-	5.47（1.58，18.90）	0.007	2^[9，13]	41	3.18（1.43，7.09）	0.005
容量相关不良事件	PBO对照	4^{[8，10，12，15]}	26	1.45（0.43，4.83）	0.55	4^{[8，10，12，15]}	0	2.03（0.60，6.83）	0.25
	活性对照	1^[13]	-	1.33（0.30，5.99）	0.71	2^[9，13]	25	0.54（0.15，1.97）	0.35

结局	干预措施	CANA 100 mg联合MET				CANA 300 mg联合MET
结局	干预措施	文献数量（篇）	I²值（%）	OR（95%CI）	P值	文献数量（篇）	I²值（%）	OR（95%CI）	P值
总不良事件	PBO对照	5^{[8，10,11,12，15]}	0	1.00（0.81，1.23）	1.00	5^{[8，10,11,12，15]}	0	1.15（0.94，1.42）	0.17
	活性对照	2^[11，13]	66	0.91（0.71，1.16）	0.44	3^{[9，11，13]}	0	1.0（0.82，1.23）	1.00
严重不良事件	PBO对照	5^{[8，10,11,12，15]}	0	0.77（0.43，1.38）	0.37	5^{[8，10,11,12，15]}	0	0.76（0.42，1.38）	0.37
	活性对照	2^[11，13]	0	0.63（0.37，1.05）	0.07	3^{[9，11，13]}	27	0.84（0.57，1.23）	0.37
尿路感染	PBO对照	5^{[8，10,11,12，15]}	0	0.90（0.54，1.51）	0.70	5^{[8，10,11,12，15]}	9	1.00（0.61，1.65）	1.00
	活性对照	2^[11，13]	0	1.46（0.85，2.53）	0.17	3^{[9，11，13]}	27	1.09（0.72，1.66）	0.68
生殖系统感染（男性）	PBO对照	4^{[8，10，12，15]}	0	3.37（0.92，12.32）	0.07	4^{[8，10，12，15]}	0	2.74（0.80，9.36）	0.11
	活性对照	1^[13]	-	5.82（1.70，20.01）	0.005	2^[9，13]	0	10.12（3.60，28.42）	<0.000 1
生殖系统感染（女性）	PBO对照	4^{[8，10，12，15]}	0	3.13（1.42，6.88）	0.005	4^{[8，10，12，15]}	0	2.73（1.23，6.06）	0.01
	活性对照	1^[13]	-	5.43（2.07，14.26）	0.000 6	2^[9，13]	0	5.29（2.82，9.91）	<0.000 01
渗透利尿相关不良事件	PBO对照	4^{[8，10，12，15]}	4	1.64（0.67，4.00）	0.27	4^{[8，10，12，15]}	30	3.20（1.47，6.97）	0.003
	活性对照	1^[13]	-	5.47（1.58，18.90）	0.007	2^[9，13]	41	3.18（1.43，7.09）	0.005
容量相关不良事件	PBO对照	4^{[8，10，12，15]}	26	1.45（0.43，4.83）	0.55	4^{[8，10，12，15]}	0	2.03（0.60，6.83）	0.25
	活性对照	1^[13]	-	1.33（0.30，5.99）	0.71	2^[9，13]	25	0.54（0.15，1.97）	0.35

Clinical Efficacy of Different Doses of Canagliflozin Combined with Metformin in the Treatment of Type 2 Diabetes Mellitus: a Meta-analysis

不同剂量卡格列净联合二甲双胍治疗2型糖尿病临床疗效的Meta分析

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 23

References 33

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	LI Yutong, ZHAO Danting, JIANG Feng, WANG Yanna, LIU Yizong, LIANG Wenjuan, LU Jiahai. Systematic Review and Meta-analysis of the Efficacy and Safety of mRNA and Recombinant Protein Subunit Vaccines Against Respiratory Syncytial Virus [J]. Chinese General Practice, 2026, 29(19): 2744-2752.
[2]	ZHANG Wenbo, WANG Junlong, ZHANG Yuping, JIANG Shuai, WANG Huaqi. The Risk of Pre-COPD Populations Progressing to COPD under Different Criteria: a Meta-analysis [J]. Chinese General Practice, 2026, 29(19): 2735-2743.
[3]	TIAN Anni, YANG Jing, SUN Jing, WANG Shichun. Effect of Robot-assisted Training on the Recovery of Hand Motor Function in Patients with Different Stages of Stroke: a Meta-analysis [J]. Chinese General Practice, 2026, 29(14): 1911-1920.
[4]	ZHAN Li, HENG Zhaoyang, HE Liangyu, ZHAO Jie, CHEN Jie, XING Jinshan. Efficacy and Safety of CAR-T Therapy Targeting the B Cell Maturation Antigen on Relapsed/Refractory Multiple Myeloma in Chinese People: a Meta-analysis [J]. Chinese General Practice, 2026, 29(14): 1921-1930.
[5]	WANG Fei, HAN Weiyu, SUN Tao. Moxibustion Combined with Three-step Therapy in the Treatment of Cancer Pain: a Network Meta-analysis [J]. Chinese General Practice, 2026, 29(09): 1203-1211.
[6]	LIU Dianchun, CHEN Xiaoying, WANG Qianyun, PAN Xingru, WEI Xuehan, WANG Bohong, WANG Ying, XUE Xue, LU Chunli. Evidence-based Pharmacological Investigation of the Clinical Practice and Rational Use of Metformin in Pre-diabetes Mellitus [J]. Chinese General Practice, 2026, 29(08): 1057-1068.
[7]	PEI Zhiyi, ZHANG Xiaoxin, LIN Jiayi, ZHANG Xiangyi, KANG Xiaofeng. Systematic Review of the Quality and Application of Patient Decision Aids in Cardiovascular Disease Based on IPDAS 4.0 Criteria [J]. Chinese General Practice, 2026, 29(07): 945-952.
[8]	ZHANG Ling, HUANG Shuangying, XU Hui, MEI Huiting, HONG Yongping. Effects of Different Exercise Types on Fall Efficacy in the Elderly: a Network Meta-analysis [J]. Chinese General Practice, 2026, 29(06): 741-751.
[9]	ZHAO Xuejiao, LI Juan, LI Yujie, LU Ting, Xian Lihong, YAN Huan. Prevalence Trends and Influencing Factors for Post-stroke Cognitive Impairment in China: a Meta-analysis [J]. Chinese General Practice, 2026, 29(03): 380-392.
[10]	ZHOU Wenchao, LIANG Jiaqi, YAO Shangman, XUE Zhao, LIU Long, GUO Xiangjie. Identification of Shared Loci between Hypertension and Parkinson's Disease [J]. Chinese General Practice, 2026, 29(02): 201-206.
[11]	XIANG Fengling, WANG Yuankun, WANG Xiaoyan, HE Shengjie, GAN Jinhua. The Prevalence of Hyperuricemia among Children and Adolescents in China: a Meta-analysis [J]. Chinese General Practice, 2025, 28(33): 4206-4213.
[12]	SHANG Luxiang, ZHU Mingqi, ZHOU Xianhui, GAO Mei, TANG Baopeng, HOU Yinglong. Prevalence and Risk Factors of Atrial Fibrillation among Adults in China: a Meta-analysis [J]. Chinese General Practice, 2025, 28(33): 4192-4198.
[13]	XU Jialan, YAN Hong, WEN Jun, ZHOU Zitong, WANG Siyu. Prevalence of Potentially Inappropriate Medication in Older Adults with Cancer: a Meta-analysis [J]. Chinese General Practice, 2025, 28(30): 3815-3822.
[14]	ZHANG Tianyu, YU Haibo, CHEN Fei, LI Xin, ZHANG Jiajia, ZHAN Xiaokai, SHEN Man, TANG Ran, FAN Sibin, ZHAO Fengyi, HUANG Zhongxia. Meta-analysis of the Efficacy and Safety of Systemic Treatment for POEMS Syndrome [J]. Chinese General Practice, 2025, 28(27): 3447-3455.
[15]	QUAN Jialin, ZHU Lin, SU Yu, CHEN Zekai, CHEN Ziqi, ZHANG Zhuofan. Research on the Improvement Effect of Exercise Modes on the Executive Function of Overweight or Obese Children or Adolescents: a Network Meta-analysis [J]. Chinese General Practice, 2025, 28(27): 3422-3431.