Efficacy and tolerability of canagliflozin as add-on to metformin in the treatment of type 2 diabetes mellitus: a meta-analysis.
OBJECTIVE
The aim of this study is to assess the efficacy and tolerability of canagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, added on to metformin in patients with type 2 diabetes mellitus (T2DM).


METHODS
Literatures were searched from major electronic databases, as well as the Chinese State Food and Drug Administration and clinicaltrials.gov for unpublished studies. Only randomized controlled trials (RCTs) comparing canagliflozin with placebo in combination with metformin were included. Two reviewers independently selected studies, evaluated the risk of bias, and extracted data. The included RCTs were analyzed by the software RevMan 5.3 provided by the Cochrane Collaboration.


RESULTS
Six RCTs were chosen for the meta-analysis. Compared to placebo, canagliflozin produced absolute reduction in glycated hemoglobin A1c (HbA1c) (-0.66% [-0.72%, -0.61%]). The proportion of patients who achieved target HbA1c was significantly greater in the canagliflozin-treated group (1.86 [1.69, 2.03]). Canagliflozin led to greater fasting plasma glucose (FPG) reduction of 1.49 mmol/L (100 mg/day) and 1.80 mmol/L (300 mg/day). Significant body weight loss of 2.09% (100 mg/day) and 2.66% (300 mg/day) with canagliflozin was observed. Canagliflozin was found to improve β cell function in terms of homeostasis model assessment (HOMA2-%B) (15.59% [12.84%, 18.35%]). Higher incidences of genital mycotic infection/female and pollakiuria (increased urine frequency) were noted with canagliflozin compared with placebo-controlled groups.


CONCLUSIONS
Canagliflozin is a potential option as an add-on to metformin based on its improvement in HbA1c, FPG, body weight, and β cell function, but further studies are demanded to strengthen this evidence. Common adverse events (AEs) like genital mycotic infection/female and pollakiuria were identified.
Department of Pharmacy, Peking University First Hospital, Beijing, 100034, People's Republic of China.
Ting
T
Yang
Department of Pharmacy, Peking University First Hospital, Beijing, 100034, People's Republic of China.
Min
M
Lu
Department of Pharmacy, Peking University First Hospital, Beijing, 100034, People's Republic of China.
Lingyue
L
Ma
Department of Pharmacy, Peking University First Hospital, Beijing, 100034, People's Republic of China.
Ying
Y
Zhou
Department of Pharmacy, Peking University First Hospital, Beijing, 100034, People's Republic of China. cuiymzy@126.com.
Yimin
Y
Cui
D000068896:Canagliflozin / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000068896:Canagliflozin; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; C517652:hemoglobin A1c protein, human
Canagliflozin; Meta-analysis; Metformin; Type 2 diabetes