A comprehensive meta-analysis on the association of SGLT2is and GLP-1RAs with vascular diseases, digestive diseases and fractures.

AIM: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are two new classes of antidiabetic agents. We aimed to evaluate the association between these two drug classes and risk of various vascular diseases, digestive diseases and fractures. METHODS: Large randomized trials of SGLT2is and GLP-1RAs were included. Outcomes of interest were the various serious adverse events related to vascular diseases, digestive diseases and fractures. We performed meta-analyses using synthesize risk ratio (RR) and 95% confidence interval (CI) as effect size. RESULTS: We included 27 large trials. SGLT2is had significant association with less hypertension (RR 0.70, 95% CI 0.54-0.91), hypertensive crisis (RR 0.63, 95% CI 0.47-0.84), varicose vein (RR 0.34, 95% CI 0.13-0.92), and vomiting (RR 0.55, 95% CI 0.31-0.97); but more spinal compression fracture (RR 1.73, 95% CI 1.02-2.92) and tibia fracture. GLP-1RAs had significant association with more deep vein thrombosis (RR 1.92, 95% CI 1.23-3.00), pancreatitis (RR 1.54, 95% CI 1.07-2.22), and cholecystitis acute (RR 1.51, 95% CI 1.08-2.09); but less rib fracture (RR 0.59, 95% CI 0.35-0.97). Sensitivity analyses suggested that our findings were robust. CONCLUSIONS: SGLT2is may have protective effects against specific vascular and digestive diseases, whereas they may increase the incidence of site-specific fractures (e.g., spinal compression fracture). GLP-1RAs may have protective effects against site-specific fractures (i.e., rib fracture), whereas they may increase the incidence of specific vascular and digestive diseases. These findings may help to make a choice between SGLT2is and GLP-1RAs in clinical practice.

Comparative efficacy and safety of pharmacological interventions for osteoporosis in postmenopausal women: a network meta-analysis (Chongqing, China).

OBJECTIVE: The aim of this study was to assess the comparative effectiveness and safety of different pharmacological agents, including abaloparatide and romosozumab, for treatment of osteoporosis in postmenopausal women. METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Google Scholar for relevant randomized controlled trials published up to July 16, 2018. After study selection according to the preplanned criteria, we performed data extraction and quality assessment. With statistical heterogeneity and inconsistency being examined, pairwise and network meta-analyses were conducted to synthesize risk ratio and 95% CI. Finally, we calculated the surface under the cumulative ranking curve to rank the interventions, and carried out three sensitivity analyses to assess the robustness of our main results. RESULTS: Our searches yielded 2,584 records in total, of which 21 were finally included in quantitative synthesis and all of them were of high quality. Our 5 outcomes of interest involved a total of 13 interventions and 67,524 participants. For each outcome, the estimated τ values all were less than or equal to 0.0747, and the P values for test of consistency varied from 0.097 to 0.941, respectively, suggesting low heterogeneity and no inconsistency. Abaloparatide and teriparatide, without statistical difference between them, had a statistically lower risk of new vertebral or nonvertebral fractures than placebo, strontium ranelate, risedronate, raloxifene, lasofoxifene (0.25 mg/d), lasofoxifene (0.5 mg/d), denosumab, and alendronate. Zoledronic acid and romosozumab, without statistical difference between them, were significantly more efficacious than placebo, risedronate, and alendronate in preventing clinical fractures. Denosumab was statistically superior to placebo in preventing new vertebral and nonvertebral fractures, and to placebo, risedronate, and alendronate in preventing clinical fractures. For the outcomes of adverse events and serious adverse events, all of treatments were not statistically different from one another, except that zoledronic acid was statistically worse than placebo in terms of adverse events. Based on surface under the cumulative ranking curves, abaloparatide and teriparatide were two of the most effective treatments in preventing new vertebral and nonvertebral fractures; zoledronic acid and romosozumab were two of the most effective treatments in preventing clinical fractures, and denosumab and romosozumab were two of the best interventions for the outcome of adverse events. Three sensitivity analyses revealed the robustness of the main results. CONCLUSIONS: Abaloparatide and teriparatide are most efficacious in preventing new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis, whereas zoledronic acid and romosozumab are in preventing clinical fractures. Meanwhile, there is no statistical difference between abaloparatide, teriparatide or romosozumab, and placebo in terms of safety. Furthermore, in terms of adverse events, zoledronic acid is statistically worse than placebo, and two of the best interventions are denosumab and romosozumab, of which denosumab also reduces the risk of different kinds of fractures.