Background: To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors.Methods: Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies andClinicaltrial.govwere searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used.Result: The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (β = − 0.461, 95% CI − 0.726 to − 0.197), PAD (β = − 0.359, 95% CI − 0.545 to − 0.172) and DF (β = − 0.476, 95% CI − 0.836 to − 0.116). Lower baseline diastolic blood pressure (β = − 0.528, 95% CI − 0.852 to − 0.205), more systolic blood pressure reduction (β = − 0.207, 95% CI − 0.390 to − 0.023) and more diastolic blood pressure reduction (β = − 0.312, 95% CI − 0.610 to − 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment.Conclusions: The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.

Aims/Introduction: To evaluate the efficacy and safety of alpha‐glucosidase inhibitors (AGI) in Asian and non‐Asian type 2 diabetes patients.Materials and Methods: Studies were identified through a literature search of MEDLINE, EMBASE and other databases until December 2016. All statistical analyses were carried out in Review Manager statistical software by computing the weighted mean difference or odds ratio and 95% confidence interval.Results: A total of 67 studies were included. AGI vs placebo: compared with the placebo, AGI treatment led to a greater decrease in hemoglobin A1c (HbA1c), fasting plasma glucose and postprandial plasma glucose. No significant difference was observed in HbA1c change, fasting plasma glucose change, postprandial plasma glucose change or incidence of hypoglycemia between Asian and non‐Asian patients. AGI vs active controls: in Asian patients, AGI treatment showed a lower reduction in HbA1c compared with dipeptidyl peptidase‐4 inhibitors and sulfonylurea. In non‐Asian patients, AGI treatment showed a lower reduction in HbA1c compared with thiazolidinedione. No significant difference was observed in HbA1c change and bodyweight change when comparing AGI with other oral hypoglycemic agents between Asian and non‐Asian patients.Conclusions: The effects of AGI treatment on glycemic control and bodyweight reduction were superior to the placebo without an increased incidence of hypoglycemia, but with an increased incidence of gastrointestinal discomforts. The hypoglycemic effects of AGI were comparable between Asian and non‐Asian patients.