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Efficacy and safety of a sodium‐glucose co‐transporter‐2 inhibitor versus placebo as an add‐on therapy for people with type 2 diabetes inadequately treated with metformin and a dipeptidyl peptidase‐4 inhibitor: a systematic review and meta‐analysis of randomised controlled trials
Author(s) -
De Buitléir C.,
O’ Connor E.,
Satti M. M.,
Shaw J.,
Liew A.
Publication year - 2021
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.14409
Subject(s) - medicine , metformin , placebo , sitagliptin , dipeptidyl peptidase 4 inhibitor , tolerability , type 2 diabetes , dipeptidyl peptidase 4 , gastroenterology , blood pressure , diabetes mellitus , pharmacology , adverse effect , endocrinology , insulin , alternative medicine , pathology
Aims To conduct a systematic review and meta‐analysis to assess the efficacy, safety and tolerability of sodium‐glucose co‐transporter‐2 inhibitors vs placebo as add‐on therapy after metformin and dipeptidyl peptidase‐4 inhibitor dual therapy in type 2 diabetes. Methods This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines (PROSPERO registration number: CRD42018099398). A search was conducted via PubMed, www.clinicaltrials.gov and Cochrane Central Register of Controlled Trials of relevant randomised controlled trials up until 14 August 2020 that compared sodium‐glucose co‐transporter‐2 inhibitors vs placebo as add‐on therapy after metformin and dipeptidyl peptidase‐4 inhibitor therapy. A random‐effects model was used. Results Six randomised controlled trials (1661 participants) met the inclusion criteria. Compared with placebo, sodium‐glucose co‐transporter‐2 inhibitor treatment, as add‐on to metformin and dipeptidyl peptidase‐4 inhibitor therapy, was associated with a significant reduction in HbA 1c level [mean difference –8 mmol/mol, 95% CI –10, –6 (–0.7%, 95% CI –0.9, –0.6); P < 0.00001], in fasting plasma glucose level [mean difference –1.70 mmol/l, 95% CI –1.91, –1.49; P < 0.00001], in weight (mean difference –1.76 kg, 95% CI –2.04, –1.48; P < 0.00001) and in blood pressure (systolic blood pressure: mean difference –3.6 mmHg, 95% CI –4.8, –2.4; P < 0.00001; diastolic blood pressure: mean difference –1.5 mmHg; 95% CI –2.4, –0.6; P = 0.002). Genital mycotic infections (odds ratio 7.37, 95% CI 3.06, 17.76; P < 0.00001) were more common with sodium‐glucose co‐transporter‐2 inhibitors, but there was no significant statistical difference in urinary tract infections (odds ratio 1.16, 95% CI 0.63, 2.13; P = 0.64), in hypoglycaemia (odds ratio 1.36, 95% CI 0.61, 3.04; P = 0.45), or in discontinuation rates due to adverse events (odds ratio 1.52, 95% CI 0.78, 2.97; P = 0.22) between the two groups. Conclusions In comparison with placebo, add‐on therapy with a sodium‐glucose co‐transporter‐2 inhibitor is significantly more efficacious in lowering HbA 1c , fasting plasma glucose and weight in people with type 2 diabetes following inadequate glycaemic control with metformin and a dipeptidyl peptidase‐4 inhibitor. The rate of discontinuation due to adverse events was similar despite higher risk of genital mycotic infections.