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Summary: In this meta‐analysis, we aim to evaluate the risk of gallbladder and biliary disease of weight management strategies and investigate the association between weight reduction and risk of gallbladder or biliary disease. Randomized controlled trials (RCTs) with a duration of at least 12 weeks that compare antiobesity medications (AOMs) with placebo or bariatric surgery with less intensive weight management strategy were concluded. Weight management strategy was associated with a significant increased risk of gallbladder or biliary disease (OR 1.361, 95% CI 1.147 to 1.614, P < 0.001, I2 = 3.5%), cholelithiasis, cholecystitis, and cholecystectomy compared with placebo or controls. The increased risk of gallbladder or biliary disease was observed both in pharmacotherapies subgroup and bariatric surgery subgroup. With regards of specific pharmacotherapies, an increased risk of gallbladder or biliary disease was observed in trials with glucagon‐like peptide 1 receptor agonist (GLP‐1 RA) treatments. In addition, trials with indication of obesity and overweight treatment and trials with higher doses showed significant higher risk of gallbladder or biliary disease compared with placebo or controls. In conclusion, weight management strategy was associated with an increased risk of gallbladder or biliary disease when compared with placebo or control groups. [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]

Aim: The aim of this study is to compare the effects of hypoglycemic treatments in groups of patients categorized according to the mean baseline body mass indexes (BMIs). Methods: Studies were identified by a literature search and all the studies were double blind, placebo-controlled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. The electronic search was first conducted in January 2015 and repeated in June 2015. Results: 227 studies were included. Treatment with sulfonylureas was compared with placebo in overweight patients and resulted in a significantly greater change in the HbA1c levels (weighted mean difference (WMD), −1.39%) compared to obese patients (WMD, −0.77%)(p<0.05). Treatment with metformin in overweight patients resulted in a comparable change in the HbA1c levels (WMD, −0.99%) compared to obese patients (WMD, −1.06%)(p>0.05). Treatment with alpha glucosidase inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.94%) that was comparable that in overweight (WMD, −0.72%) and obese patients (WMD, −0.56%)(p>0.05). Treatment with thiazolidinediones in normal weight patients was associated with a HbA1c change (WMD, −1.04%) that was comparable with that in overweight (WMD, −1.02%) and obese patients (WMD, −0.88%)(p>0.05). Treatment with DPP-4 inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.93%) that was comparable with that in overweight (WMD, −0.66%) and obese patients (WMD, −0.61%)(p>0.05). In total, of the seven hypoglycemic agents, regression analysis indicated that the mean baseline BMI was not associated with the mean HbA1c changes from baseline. Conclusion: In each kind of hypoglycemic therapy in type 2 diabetes, the baseline BMI was not associated with the efficacy of HbA1c changes from baseline. [ABSTRACT FROM AUTHOR]

Background: As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear.Methods: Double-blind randomized controlled trials comparing the efficacy of initial combination therapy of metformin and DPP-4 inhibitors with metformin monotherapy were included. The primary outcome was a result of comparisons between high-dose combination therapy and low-dose combination therapy in terms of efficacy and safety.Results: A total of 11 studies were included. The results indicated that the high-dose combination therapy showed significant decreases in hemoglobin A1c (HbA1c) (-0.32%, P < 0.05), fasting plasma glucose (FPG) (-0.63 mmol/L, P < 0.05), and postprandial glucose (PPG) (-0.99 mmol/L, P < 0.05), but less increase in body weight (-0.54 kg, P < 0.05) when compared with low-dose combination therapy, corrected by metformin monotherapy. Moreover, the high-dose combination therapy exhibited significant decreases in HbA1c (-0.24%, P < 0.05), FPG (-0.54 mmol/L, P < 0.05), and PPG (-0.94 mmol/L, P < 0.05) in the Caucasian population than in the Asian population, corrected by metformin monotherapy.Conclusion: As an initial treatment, the high dose of metformin in combination with DPP-4 inhibitors not only provided better glycemic control but also had less effect on weight gain compared with the low-dose combination therapy through the correction of metformin monotherapy. Moreover, initial combination therapy in the Caucasian population showed better glycemic control and less increase in body weight compared with the Asian population. [ABSTRACT FROM AUTHOR]

Background: The aim of this meta-analysis was to assess the comprehensive clinical efficacy of dipeptidyl peptidase-IV (DPP-4) inhibitors in Chinese type 2 diabetes patients and to evaluate whether there is a different response to treatment with different kinds of DPP-4 inhibitors in those patients.Methods: Databases were systematically searched, and qualifying clinical studies of Chinese type 2 diabetes patients were included.Results: A total of 30 studies were included. Treatment with saxagliptin resulted in a significantly greater change from baseline in HbA1c levels (weighted mean difference [WMD], -1.28%; 95% CI, -1.37% to -1.19%); treatment with sitagliptin led to a significantly greater change from baseline (WMD, -1.17%; 95% CI, -1.46% to -0.89%); treatment with vildagliptin was associated with a significantly greater change in HbA1c levels (WMD, -0.77%; 95% CI, -0.88% to -0.65%); treatment with linagliptin led to a significantly greater change (WMD, -0.84%; 95% CI, -0.92% to -0.75%); and treatment with alogliptin also led to a significantly greater change (WMD, -0.91%; 95% CI, -1.48% to -0.33%). In terms of body weight, treatment with saxagliptin was associated with no significant decreases in Chinese type 2 diabetes mellitus (T2DM) patients (WMD, -0.17 kg, 95% CI, -4.26 to 3.92 kg). Treatment with sitagliptin and linagliptin was also associated with no significant changes in body weight (WMD, 0.16 and 0.11 kg, respectively, P > 0.05).Conclusions: In Chinese type 2 diabetes patients, the efficacy of glucose control in all five kinds of DPP-4 inhibitor treatments was well confirmed, and no significant change in body weight was found. [ABSTRACT FROM AUTHOR]

Whether colchicine reduces the levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) remains uncertain. Therefore, this systematic review and meta-analysis were conducted to evaluate the overall effect of colchicine treatment on hs-CRP and IL-6 levels in patients with coronary artery disease (CAD). PubMed/Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published before October 2021. Clinical trials in patients with CAD with reports of hs-CRP and IL-6 level changes before and after colchicine intervention were included. In total, 11 trials on hs-CRP and two trials on IL-6 were included in this meta-analysis. Compared with that in the control group, colchicine treatment was significantly associated with decreased hs-CRP levels (weighted mean differences [WMDs], −0.81 mg/L; 95% confidence interval [CI], −1.34 to −0.28 mg/L; P = 0.003) in patients with CAD. Besides, the levels of IL-6 were significantly reduced in colchicine users compared to that of placebo (WMD, −1.28 pg/mL; 95% CI, −2.35 to −0.21 pg/mL; P = 0.02). In a subgroup analysis, colchicine led to a significant reduction in hs-CRP levels in studies with duration of intervention >7 days (WMD, −0.65 mg/L; 95% CI, −1.08 to −0.21 mg/L; P = 0.004) and studies with baseline hs-CRP levels ≥3.0 mg/L (WMD, −0.99 mg/L; 95% CI, −1.92 to −0.06 mg/L; P = 0.04). Colchicine intervention was associated with a reduction in hs-CRP and IL-6 levels in patients with CAD. Future investigations are required to verify the effect of colchicine on inflammatory markers and clarify the potential mechanisms of the cross talk between colchicine, inflammation, and cardiovascular outcomes. • Comparing with that in the control group, colchicine intervention was associated with a reduction in hs-CRP and IL-6 levels in patients with coronary artery disease. • The administration of 1 mg colchicine daily could lead to a more substantial reduction in hs-CRP levels than that of a 0.5 mg daily dose. • Patients with the following characteristics had a trend of benefiting from colchicine: ACS, duration >7 days, and baseline hs-CRP level ≥3.0 mg/L. [ABSTRACT FROM AUTHOR]

• Denosumab or romosozumab treatment did not increase the risk of composite CV outcomes, 3 P MACE, and specific cardiovascular events among elderly men and postmenopausal woman with osteoporosis. • Romosozumab might increase 4 P MACE among elderly men and postmenopausal woman with osteoporosis. • For composite CV endpoints, denosumab or romosozumab treatment did not increase the risk in any of the subgroup analyses regardless of sex, the control treatment, BMD T-score, and follow-up duration. • Studies with longer term follow-up and specific attention to cardiovascular events may enhance our understanding of denosumab or romosozumab therapy. Osteoporosis and cardiovascular (CV) diseases are closely correlated. RANKL/RANK/OPG pathway and Wnt signalling pathway both implicated in the pathogenesis of osteoporosis and cardiovascular diseases. We aimed to investigate the effect of denosumab or romosozumab therapy on cardiovascular outcomes in patients with primary osteoporosis. PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to June 4, 2019. Randomized clinical trials evaluating the effect of denosumab or romosozumab versus active comparators or placebo for at least 6 months in patients with primary osteoporosis or osteopenia were included. Two investigators independently extracted data for study characteristics, outcomes of interest, and risk of bias in accordance with PRISMA guidelines. 17 relevant studies (denosumab: n = 11, 13615 participants; romosozumab: n = 6, 12219 participants) were included. No associations between denosumab therapy and risk of a composite cardiovascular outcome (1.06 [95 % CI, 0.88–1.28], p = 0.54), three-point major adverse cardiovascular event (3P MACE, 1.01 [95 % CI, 0.83–1.23], p = 0.93), and four-point major adverse cardiovascular event (4P MACE, 0.99 [95 % CI, 0.83–1.18], p = 0.89) were identified. Romosozumab therapy did not increase the risk of composite cardiovascular outcome (1.26 [95 % CI, 0.95–1.68], p = 0.11), and 3P MACE (1.41 [95 % CI, 0.99–2.02], p = 0.06), while increased the risk of 4P MACE (1.39 [95 % CI, 1.01–1.90], p = 0.04) among elderly men and postmenopausal woman with osteoporosis over a period of 12–36 months. Denosumab or romosozumab did not increase or reduce specific cardiovascular outcomes, including CV death or death, myocardial infarction, stroke, atrial fibrillation, heart failure, aortic and intracranial aneurysm, aortic dissection, aortic valve disease and hypertension (all p ＞0.05). Sensitivity analysis conducted by random effects model altered the result of 4 P MACE in romosozumab (1.36 [0.99–1.87], p = 0.06). No other significant difference was detected in the sensitivity analyses and subgroup analyses. Denosumab therapy was not associated with any risk of composite and specific cardiovascular outcomes among patients with primary osteoporosis than active comparators or placebo, while romosozumab therapy might increase the risk of 4 P MACE. [ABSTRACT FROM AUTHOR]