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The association between sodium-glucose cotransporter 2 inhibitors (SGLT2is) and various cardiovascular and respiratory diseases is unestablished. This meta-analysis aimed to explore whether use of SGLT2is is significantly associated with the occurrences of 80 types of cardiovascular diseases and 55 types of respiratory diseases. Large randomized trials of SGLT2is were included in analysis. Meta-analysis was conducted to synthesize risk ratio (RR) and 95% confidence interval (CI). Nine large trials were included in analysis. Compared to placebo, SGLT2is were associated with the reduced risks of 9 types of cardiovascular diseases (e.g., atrial fibrillation [RR 0.78, 95% CI 0.67-0.91], bradycardia [RR 0.60, 95% CI 0.40-0.89], and hypertensive emergency [RR 0.29, 95% CI 0.12-0.72]) and 11 types of respiratory diseases (e.g., chronic obstructive pulmonary disease [RR 0.77, 95% CI 0.61-0.97], asthma [RR 0.57, 95% CI 0.35-0.95], and sleep apnoea syndrome [RR 0.36, 95% CI 0.15-0.87]). The results of random-effects meta-analysis were similar with those of fixed-effects meta-analysis. No heterogeneity or only little heterogeneity was found in most meta-analyses. No publication bias was observed in most of the meta-analyses conducted in this study. SGLT2is were not significantly associated with the other 115 cardiovascular and respiratory diseases. SGLT2is are associated with the reduced risks of 9 types of cardiovascular diseases (e.g., atrial fibrillation, bradycardia, and hypertensive emergency) and 11 types of respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma, and sleep apnoea syndrome). This proposes the potential of SGLT2is to be used for prevention of these cardiovascular and respiratory diseases.

The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I 2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I 2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I 2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I 2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

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Background: The factors affecting the efficacy of gliflozins in patients with heart failure (HF) are not clear. We aimed to evaluate the effects of 11 important factors on the efficacy of gliflozins in HF patients. Methods: Randomized trials assessing gliflozins in HF patients were included. The outcome of interest was composite HF outcome, a composite of cardiovascular death, or hospitalization for HF. Meta-analysis was done according to 11 factors: status of type 2 diabetes, sex, use of angiotensin receptor-neprilysin inhibitor, age, history of hospitalization for HF, estimated glomerular filtration rate, body mass index, New York Heart Association (NYHA) class, race, region, and left ventricular ejection fraction. Results: Compared with placebo, gliflozins reduced the risk of composite HF outcome by 14% in the subgroup of patients with NYHA class III or IV (hazard ratios [HR] 0.86, 95% confidence intervals [CI] 0.75–0.99), by 34% in the subgroup of patients with NYHA class II (HR 0.66, 95% CI 0.59–0.74), and by 85% in the subgroup of patients with NYHA class I (HR 0.15, 95% CI 0.03–0.73). This between-group difference was approximate to statistical significance ( P subgroup = .06). The benefit of gliflozins in HF patients was not affected by the other 10 factors ( P subgroup ≥ .123). Conclusions: Gliflozins are applicable for a broad population of HF patients as for preventing HF events, while gliflozins may lead to greater benefits in patients with mild HF than in those with moderate to severe HF.