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Aims: To elucidate the association between baseline renal characteristics and the disparities in renal outcomes among patients with SGLT2i treatment. Methods: Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov were searched from inception to November 2022. Event-driven randomized controlled trials of SGLT2i with reports of renal outcomes were included. Sensitivity analyses of prespecified eGFR and UACR subgroups were conducted. Results: Generally, compared with placebo, the use of SGLT2i was associated with improved renal prognosis (HR = 0.64, 95%CI 0.59–0.70). The magnitude of risk reductions in composite renal outcomes between SGLT2i versus placebo was comparable among different eGFR stratifications (normal renal function: HR = 0.49, 95%CI 0.31–0.79; mild renal impairment: HR = 0.57, 95%CI 0.48–0.68; moderate renal impairment: HR = 0.70, 95%CI 0.63–0.78; severe renal impairment: HR = 0.72, 95%CI 0.62–0.84; P for subgroup difference = 0.09). However, renal benefits seemd to be more prominent in normal to mildly increased albuminuria stratum (HR = 0.51, 95%CI 0.39–0.66) and severely increased albuminuria stratum (HR = 0.57, 95%CI 0.47–0.68), when compared with moderately increased albuminuria stratum (HR = 0.79, 95%CI 0.65–0.96; P for subgroup difference = 0.01). Conclusions: Generally, the use of SGLT2i was consistently associated with decreased risk of renal events in all prespecified eGFR and albuminuria spectrums, even in patients with substantial renal impairment. The renal benefits of SGLT2i seemed to be independent of baseline eGFR, while the risk reduction in renal events was more profound among patients with mildly increased albuminuria or severely increased albuminuria. [ABSTRACT FROM AUTHOR]

To assess the association between the use of sodium–glucose cotransporter 2 inhibitor (SGLT2i) and the incidence of diabetic retinopathy (DR). PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were searched from inception to October 2021. Randomized controlled trials (RCTs) with reports of incidence of DR and other eye disorders between SGLT2i and non-SGLT2i users with type 2 diabetes mellitus were included. In general, the incidences of DR were comparable between SGLT2i and non-SGLT2i users (OR = 0.80, 95%CI 0.61 to 1.06, P = 0.12). However, compared with non-SGLT2i users, the incidence of DR was significantly reduced in SGLT2i users with diabetes duration less than 10 years (OR = 0.32, 95%CI 0.13 to 0.76, P = 0.01). Weight reduction in SGLT2i users was associated with a decreased risk of retinal detachment. Moreover, longer study duration was associated with lower incidence of cataract and retinal vasculopathy in SGLT2i users. In general, the use of SGLT2i was not associated with the incidence of DR. However, a reduced risk of DR was observed in SGLT2i users with diabetes duration less than 10 years. An early initiation of SGLT2i might be more likely to provide with ocular benefits. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

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 and Clinicaltrial.gov were 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. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: To evaluate whether there is disparity of the efficacy and all‐cause mortality and other adverse effects between Asian and non‐Asian patients with sodium–glucose cotransporter 2 (SGLT2) inhibitors treatment. Materials and Methods: Randomized clinical trials publicly available before January 2017, comparing SGLT2 inhibitors treatment with a placebo in type 2 diabetes patients were identified. The association between treatment and outcomes was estimated by computing the weighted mean difference for glycated hemoglobin level, blood pressure level, lipid profile levels and bodyweight, and the odds ratios for adverse events. Results: A total of 17 trials with Asian patients were included and 39 trials with non‐Asian patients were included. Comparison of the glycated hemoglobin decreases corrected by a placebo between Asian and non‐Asian patients showed that there was a non‐significant difference of 0.05% between groups (P > 0.05). Comparisons of the bodyweight changes and blood pressure changes corrected by a placebo between Asian and non‐Asian patients did not show a significant difference between groups (P > 0.05). The risk of all‐cause mortality was not increased when compared with a placebo both in Asian and non‐Asian populations, and the risk of genital infection in Asian and non‐Asian populations were both significant increased. Conclusions: Overall, according to the present meta‐analysis, comparison of the efficacy in SGLT2 inhibitors treatment between Asian and non‐Asian type 2 diabetes patients showed no significant difference in glycated hemoglobin reduction and bodyweight reduction. Furthermore, no disparity was found in the risk of all‐cause mortality or hypoglycemia in SGLT2 inhibitors treatment between Asian and non‐Asian patients. [ABSTRACT FROM AUTHOR]

Aims/Introduction To evaluate the efficacy of weight changes from baseline of the sodium-glucose cotransporter 2 (SGLT2) inhibitors treatment and glucagon-like peptide-1 (GLP-1) analogs treatment after comparisons with a placebo in type 2 diabetes patients, and the associated factors. Materials and Methods Studies were searched from when recording began, June 2004, until June 2015, and re-searched in July 2016, and placebo-controlled randomized trials in type 2 diabetes patients with a study length of ≥12 weeks were included. Results A total of 97 randomized controlled trials were included. Compared with a placebo, treatment with SGLT2 inhibitors was associated with a significantly greater decrease in weight change from baseline (weighted mean differences −2.01 kg, 95% confidence interval −2.18 to −1.83 kg, P < 0.001). Compared with a placebo, changes with GLP -1 treatment were also associated with a comparable decrease in weight change from baseline (weighted mean differences −1.59 kg, 95% confidence interval −1.86 to −1.32 kg, P < 0.001). Meta-regression analysis showed that the baseline age, sex, baseline glycated hemoglobin, diabetes duration or baseline body mass index were not associated with the weight change from baseline in SGLT2 inhibitors or in GLP-1 treatment corrected by placebo. Comparisons of weight changes from baseline corrected by placebo between SGLT2 inhibitors and GLP-1 treatment showed that the difference was not significant ( P > 0.05). Conclusions According to the present meta-analysis, treatment with SGLT2 inhibitors and treatment with GLP-1 analogs led to comparable weight changes from baseline, which are both with significance when compared with placebo treatment. [ABSTRACT FROM AUTHOR]