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Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on asthma, which is often comorbid with type 2 diabetes mellitus (T2DM) and obesity. Therefore, we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1 (GLP-1) receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were systematically searched from inception to July 2023. Randomized controlled trials (RCTs) of GLP-1 receptor-based agonists (GLP-1RA, GLP-1 based dual and triple receptor agonist) with reports of asthma events were included. Outcomes were computed as risk ratios (RR) using a fixedeffects model. Overall, 39 RCTs with a total of 85,755 participants were included. Compared to non-GLP-1 receptor-based agonist users, a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments, although the difference was not statistically significant [ RR = 0.91, 95% confidence interval (CI): 0.68 to 1.24]. Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users (RR = 0.65, 95% CI : 0.43 to 0.99, P = 0.043). We also performed sensitivity analyses for participant characteristics, study design, drug structure, duration of action, and drug subtypes. However, no significant associations were observed. Compared with non-users, a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments. Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma. [ABSTRACT FROM AUTHOR]

Glucokinase variant-induced maturity-onset diabetes of the young (GCK-MODY) exhibits the unique clinical features of mild fasting hyperglycemia. However, formal studies of its glucose excursion pattern in daily life in comparison with those with or without other types of diabetes are lacking. We conducted a case-control study including 25 patients with GCK-MODY, 25 A1C-matched, drug-naive patients with type 2 diabetes (T2DM), and 25 age-, BMI-, and sex-matched subjects with normal glucose tolerance (NGT). All the subjects wore flash glucose monitoring (FGM) sensors for 2 weeks, and glucose readings were masked. Glucose excursion was significantly lower in the GCK-MODY than that in A1C-matched T2DM during the daytime, but was similar during the nighttime. The daytime coefficient of variation (CV) driven by postprandial glucose could separate GCK-MODY from well-controlled T2DM, but the nighttime CV could not. In discriminating between GCK-MODY and T2DM, the area under the curve of the CV was 0.875. However, in GCK-MODY and NGT subjects, the CVs were similar at 24 h, whereas the other four excursion parameters were significantly higher in GCK-MODY than those in NGT subjects. FGM confirmed the stability and mildness of hyperglycemia in GCK-MODY patients. Postprandial regulation is a key driver of the difference in excursion between GCK-MODY and T2DM. [ABSTRACT FROM AUTHOR]

Aim: To assess the population attributable fractions (PAFs) for modifiable risk factors for microvascular complications of type 2 diabetes (T2D) in China. Materials and Methods: Data collected from the China National HbA1c Surveillance System from 2009 to 2013 were used. The PAFs of four predefined risk factors, including an HbA1c of 7% or higher, blood pressure (BP) of 130/80 mmHg or higher, low‐density lipoprotein‐cholesterol (LDL‐C) of 1.8 mmol/L or higher and body mass index (BMI) of 24 kg/m2 or higher, were calculated for diabetic microvascular complications, including diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN). PAFs were further adjusted for age, sex and duration of diabetes. Results: In total, there were 998 379 participants with T2D from nationwide mainland China included in this analysis. As for DR, an HbA1c of 7% or higher, BP of 130/80 mmHg or higher, LDL‐C of 1.8 mmol/L or higher and BMI of 24 kg/m2 or higher conferred PAFs of 16.2%, 15.2%, 5.8% and 2.8%, respectively. In the case of DKD, BP of 130/80 mmHg or higher provided a PAF of 25.2%, followed by an HbA1c of 7% or higher (13.9%), BMI of 24 kg/m2 or higher (8.0%) and LDL‐C of 1.8 mmol/L or higher (5.6%). As for DSPN, an HbA1c of 7% or higher, BP of 130/80 mmHg or higher, LDL‐C of 1.8 mmol/L or higher and BMI of 24 kg/m2 or higher contributed to PAFs of 14.2%, 11.7%, 5.9% and 5.8%, respectively. PAFs for diabetic microvascular complications were mildly to moderately reduced after adjusting for participants' age, sex and duration of diabetes. Conclusions: Suboptimal glycaemic and BP control were the main contributors to diabetic microvascular complications, while the PAFs of unmet LDL‐C and BMI control targets were quite limited for diabetic microvascular complications. In addition to glycaemic control, BP control should be especially prioritized in the management of diabetic microvascular complications to further reduce the disease burden. [ABSTRACT FROM AUTHOR]

To assess the influence of steady-state concentration, duration of action and molecular weight of glucagon-like peptide-1 receptor (GLP-1RA) on efficacy and gastrointestinal (GI) side effects in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to April 2022. Randomized controlled trials (RCTs) comparing GLP-1RA versus non-GLP-1RA agents in patients with T2DM were included. Sensitivity analyses on steady-state concentration, duration of action and molecular weight of GLP-1RA were conducted. 113 RCTs were included. Greater HbA1c reduction between GLP-1RA users versus non-GLP-1RA users was observed in the high-steady-state-concentration stratum and long-acting stratum compared with the low-steady-state-concentration stratum (Psubgroup difference = 0.0004) and short-acting stratum (Psubgroup difference<0.0001). The risk of GI adverse events in GLP-1RA users versus non-GLP-1RA users was decreased in the high-steady-state-concentration stratum, long-acting stratum and heavy-molecular-weight stratum compared with low-steady-state-concentration stratum (Psubgroup difference<0.0001), short-acting stratum (Psubgroup difference = 0.002) and light-molecular-weight stratum (Psubgroup difference = 0.0008). GLP-1RA with high steady-state concentration and long duration of action showed better hypoglycemic effect. GLP-1RA with high steady-state concentration, long duration of action and heavy molecular weight was associated with lower risk of GI adverse events. [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]

Aims: This meta‐analysis aimed to evaluate the risk of developing bullous pemphigoid (BP) and other skin‐related adverse events (AEs) in patients with type 2 diabetes (T2DM) undergoing dipeptidyl peptidase‐4 inhibitor (DPP‐4i) treatment in randomized controlled trials (RCTs). Methods: In this meta‐analysis, the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs, which involve patients with T2DM reporting skin‐related AEs. RCTs that comparatively evaluated the effects of DPP‐4i treatment and placebo on patients with T2DM and reported skin‐related AEs were included in the analysis. The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Peto's methods. The GRADE approach was used to rate the quality of evidence. Results: A total of 46 randomized placebo‐controlled trials, including 3 trials with reports of BP (n = 38 011), that reported skin‐related AEs were included (n = 59 332). Compared to the placebo group, the risk of developing BP was significantly higher in the DPP‐4i treatment group (OR = 7.38, 95% CI 2.00‐27.25, I2 = 0%, P =.003; quality rating: very low). Additionally, DPP‐4i treatment was associated with an increased overall risk of developing skin‐related AEs (OR = 1.22, 95% CI 1.02‐1.46, I2 = 32%, P =.03; quality rating: moderate). Conclusions: This meta‐analysis suggested that treatment with DPP‐4is, including sitagliptin, saxagliptin, and linagliptin, was associated with an increased risk of developing BP. Additionally, the risk of developing skin‐related AEs increased when all DPP‐4is were combined. Skin lesion, especially BP, should be monitored in patients with diabetes undergoing DPP‐4i treatment. Future studies should evaluate the susceptible population and develop strategies for early detection of skin‐related AEs. [ABSTRACT FROM AUTHOR]

Objective: Whether hypoglycemic treatments with weight-alternating effects influence the incidence of neoplasm in type 2 diasbetes (T2D) remains uncertain. Therefore, we performed a meta-analysis to assess the association between the weight alteration and incidence of neoplasm in patients with T2D. Research Design and Methods: Systematic searches were conducted for studies published between the inception of 1950s and September 2019. Randomized controlled trials conducted in T2D patients with at least 48-week follow-up, significant weight change difference between treatment arms and reports of neoplasm events were included. Fixed-effects model and meta-regression analysis were accordingly used. Results: In all, 46 studies were included. Analysis indicated weight reduction was not associated with a decreased incidence of neoplasm (OR = 1.01, 95% CI, 0.96 to 1.07, I 2 = 17%) and weight elevation was not associated with an increased incidence of neoplasm (OR = 0.91, 95% CI, 0.76 to 1.09, I 2 = 0%). Meta-regression analysis showed a slower weight reduction rate (β = −5.983, 95% CI, −11.412 to 0.553, P = 0.03) instead of weight change difference (β = −0.030, 95% CI, −0.068 to 0.007, P = 0.115) was significantly associated with reduced risk of neoplasm in patients with T2D. Moreover, a decreased incidence of prostate, bladder, and uterine neoplasm was observed in T2D patients with weight reduction difference while an increased incidence of thyroid neoplasm was found in glucagon-like peptide-1 receptor analog (GLP-1RA) users with weight reduction difference. Conclusions: Additional weight change achieved by current hypoglycemic agents or strategies in short and medium periods was not associated with incidence of most neoplasm in patients with T2D. However, a decreased incidence of prostate, bladder, and uterine neoplasm was shown in T2D patients with weight reduction difference while an increased risk of thyroid neoplasm was observed in T2D patients on GLP-1RA treatments with weight reduction difference. A more sustained and persistent weight reduction process may confer reduced risk of neoplasm in patients with T2D. [ABSTRACT FROM AUTHOR]

Background: The placebo response in patients with diabetes mellitus is very common. A systematic evaluation needs to be updated with the current evidence about the placebo response in diabetes mellitus and the associated factors in clinical trials of anti-diabetic medicine.Methods: Literature research was conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies published between the date of inception and June 2019. Randomized placebo-controlled trials conducted in type 1and type 2 diabetes mellitus (T1DM/T2DM) were included. Random-effects model and meta-regression analysis were accordingly used. This meta-analysis was registered in PROSPERO as CRD42014009373.Results: Significantly weight elevation (effect size (ES) = 0.33 kg, 95% CI, 0.03 to 0.61 kg) was observed in patients with placebo treatments in T1DM subgroup while significantly HbA1c reduction (ES = - 0.12%, 95% CI, - 0.16 to - 0.07%) and weight reduction (ES = - 0.40 kg, 95% CI, - 0.50 to - 0.29 kg) were observed in patients with placebo treatments in T2DM subgroup. Greater HbA1c reduction was observed in patients with injectable placebo treatments (ES = - 0.22%, 95% CI, - 0.32 to - 0.11%) versus oral types (ES = - 0.09%, 95% CI, - 0.14 to - 0.04%) in T2DM (P = 0.03). Older age (β = - 0.01, 95% CI, - 0.02 to - 0.01, P < 0.01) and longer diabetes duration (β = - 0.02, 95% CI, - 0.03 to - 0.21 × 10-2, P = 0.03) was significantly associated with more HbA1c reduction by placebo in T1DM. However, younger age (β = 0.02, 95% CI, 0.01 to 0.03, P = 0.01), lower male percentage (β = 0.01, 95% CI, 0.22 × 10-2, 0.01, P < 0.01), higher baseline BMI (β = - 0.02, 95% CI, - 0.04 to - 0.26 × 10-2, P = 0.02), and higher baseline HbA1c (β = - 0.09, 95% CI, - 0.16 to - 0.01, P = 0.02) were significantly associated with more HbA1c reduction by placebo in T2DM. Shorter diabetes duration (β = 0.06, 95% CI, 0.06 to 0.10, P < 0.01) was significantly associated with more weight reduction by placebo in T2DM. However, the associations between baseline BMI, baseline HbA1c, and placebo response were insignificant after the adjusted analyses.Conclusion: The placebo response in diabetes mellitus was systematically outlined. Age, sex, disease severity (indirectly reflected by baseline BMI and baseline HbA1c), and disease duration were associated with placebo response in diabetes mellitus. The association between baseline BMI, baseline HbA1c, and placebo response may be the result of regression to the mean. [ABSTRACT FROM AUTHOR]

Background. To develop a decision-support software according to the Chinese Diabetes Society guideline in order to improve the standard care in type 2 diabetes. Methods. Firstly, we developed a decision-support software for healthcare professionals. It was an independent software on a tablet to record the data of patients and treatments given by their physicians. A major function of the software was to remind doctors when and how they should implement the standard care as recommended by the Chinese Diabetes Society guideline. Secondly, we compared the baseline data of standard care including statin and aspirin usage with data from a previous "3B study" to see whether there was an improvement of these standard cares. Finally, we further compared the data during four quarters of the whole year to evaluate whether there was a continuous improvement. Results. During the first quarter, 27,291 cases and 27,352 cases were collected with complete information about statin and aspirin usage, respectively. The percentage of patients treated with statins and aspirin in our study was significantly higher than that reported in the 3B study (59.6% vs. 19.9% and 59.8% vs. 18.5%, P<0.001). There were no significant differences among the four quarters for the percentage of the patients who were taking statin or aspirin (P>0.05). Conclusion. Our decision-support software has been shown to be effective in continuously improving the standardization of comprehensive treatment in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase‐4 (DPP‐4) inhibitors compared with combining insulin therapy with a placebo or other antihyperglycemic agents. Materials and Methods: A literature search was carried out via electronic databases. The inclusion criteria were randomized controlled trials comparing the addition of DPP‐4 inhibitors to insulin with the addition of a placebo or other active hypoglycemic agents to insulin therapy, study duration of no less than 12 weeks carried out in type 2 diabetes patients and the availability of outcome data to evaluate a change in the glycated hemoglobin. Results: The glycated hemoglobin‐lowering efficacy was significantly greater with DPP‐4 inhibitor/insulin (DPP‐4i/INS) than with placebo/insulin (weighted mean difference −0.53%, 95% confidence interval −0.63, −0.43, P < 0.01). The postprandial plasma glucose‐lowering efficacies was also significantly greater with DPP‐4i/INS than with placebo/insulin (weighted mean difference −1.65 mmol/L, 95% CI: −2.34, −0.96, P < 0.05). The risk of hypoglycemia or severe hypoglycemia was similar for DPP4i/INS and placebo/insulin treatments. There was no significant difference in the glycemia‐lowering efficacy between DPP‐4i/INS and alpha‐glucosidase inhibitors/insulin, thiazolidinedione/insulin and glucagon‐like peptide‐1 receptor agonist/insulin. Sodium–glucose cotransporter 2 inhibitor/insulin treatment achieved better placebo‐corrected efficacy in lowering postprandial plasma glucose, with less weight gain and no higher risk of hypoglycemia. Conclusions: Treatment with DPP‐4 inhibitors combined with insulin improved glycemic control without an increased risk of hypoglycemia or weight gain compared with insulin treatment alone. [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]

Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors.Methods: Overall, 55 placebo-controlled trials were included.Results: The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1.30 kg, -1.51 kg, -1.79 kg, -2.24 kg, respectively; P < 0.001). Treatment with 50 mg, 100 mg, 200 mg, and 300 mg of canagliflozin also led to significant decreases in weight (WMD, -1.20 kg, -1.82 kg, -1.83 kg, -2.37 kg, respectively; P < 0.001). In the treatment with empagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin, body weight also significantly decreased. The decrease in weight was associated with the dosage of dapagliflozin (P < 0.05).Conclusions: Body weight significantly decreased in patients with type 2 diabetes who received different dosages of SGLT2 inhibitors compared with patients who received a placebo. Moreover, in patients treated with dapagliflozin, there was a statistically significant dosage-dependent trend in body weight reduction. [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]

Objective: The prevalence of type 2 diabetes is increasing rapidly in the young population. The clinical characteristics and risk factors for young type 2 diabetes patients with atherosclerosis are not fully explicated. The aim of the present study was to investigate various clinical and biochemical characteristics of young type 2 diabetic patients with atherosclerosis. Design and Methods: This was a cross-sectional study. The study involved 2199 hospitalized patients with type 2 diabetes. The young patients were classified into the atherosclerotic group or the non-atherosclerotic group, and we also enrolled an older group with peripheral atherosclerosis disease and an age of at least 45 years. Comparisons were made between the different groups to investigate the cardiovascular and metabolic risk profiles of young type 2 diabetes patients with atherosclerosis. We also used logistic regression models to assess the atherosclerosis risk factors for young patients. Results: Compared to older type 2 diabetes patients with atherosclerosis, young patients with atherosclerosis had more deleterious profiles of weight and hyperlipidemia. Only age and diabetes duration were found to be significant independent risk factors for atherosclerosis in young patients. The ratio of the presence of atherosclerosis in the lower extremity arteries alone was significantly higher in young patients than older patients (26.4% vs. 14.0%, P = 0.000). Conclusion: Young type 2 diabetes patients with atherosclerosis have more adverse cardiovascular risk profiles and inadequate control of these risk factors. Lower extremity examination is of high importance in young patients. [ABSTRACT FROM AUTHOR]

Background: To evaluate the risk of infections in the treatment of type 2 diabetes patients with dipeptidyl-peptidase 4 (DPP-4) inhibitors.Methods: A literature search was conducted through electronic databases. The inclusion criteria included study duration of no less than 12 weeks developed in type 2 diabetes patients, the use of a randomized control group receiving a DPP-4 inhibitor and the availability of outcome data for infections. Out of 2181 studies, 74 studies were finally included.Results: The risk of overall infection for DPP-4 inhibitors treatment was comparable to placebo (odds ratio (OR) = 0.97, 95% confidence interval (CI), 0.91 to 1.04, p = 0.40), metformin treatment (OR = 1.22, 95% CI, 0.95 to 1.56, p = 0.12), sulphonylurea treatment (OR = 1.09, 0.93 to 1.29, p = 0.29), thiazolidinedione treatment (OR = 0.86, 95% CI, 0.65 to 1.14, p = 0.29) and alpha glucosidase inhibitor treatment (OR = 1.03, 95% CI, 0.33 to 3.22, p = 0.96). When compared different DPP-4 inhibitors with placebo treatment, risks of infections were comparable for alogliptin, linagliptin, sitagliptin, saxagliptin and vildagliptin. Compared with placebo or active comparator treatment, risks of infection in different systems for DPP-4 inhibitors were all comparable.Conclusions: The overall risk of infections of DPP-4 inhibitor was not increased compared with control groups. [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]

• Disparities were found in the cardiorenal outcomes among different GLP-1RAs. • GLP-1RAs with high concentration was associated with less cardiorenal events. • Long acting GLP-1RAs was associated more improved cardiovascular outcomes. • The molecular weight of GLP-1RAs did not influence the cardiorenal outcomes. Disparities were found in the cardiovascular and renal outcomes among different glucagon-like peptide 1 receptor agonist (GLP-1RA) subtypes. However, whether the characteristics of GLP-1RA itself are associated with these disparities remains unclear. To assess the association between the steady-state concentration, duration of action, or molecular weight of GLP-1RA and the risks of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). PubMed, MEDLINE, EMBASE, Cochrane and Clinicaltrial.gov from inception to April 2022. Randomized controlled trials (RCTs) investigating GLP-1RAs in patients with T2D were included. Literature screening and data extraction were performed independently by 2 researchers. The outcomes were computed as odds ratio (OR) and its 95% confidence interval (CI). Subgroup analyses were conducted according to steady-state concentration, duration of action and molecular weight of GLP-1RAs. Primary outcomes were major adverse cardiovascular events (MACE), composite renal outcome and all-cause mortality. In all, 61 RCTs were included. When compared with non-GLP-1RA agents, GLP-1RAs with high steady-state concentration were associated with greater risk reduction in MACE (p for subgroup difference = 0.01) and the composite renal outcome (p for subgroup difference = 0.008) in patients with T2D. Greater risk reductions in MACE between GLP-1RA users versus non-GLP-RA users were observed in long acting stratum when compared with short acting stratum (p for subgroup difference = 0.04) in patients with T2D. The molecular weight of GLP-1RAs was not associated with the risk of cardiovascular and renal outcomes. GLP-1RAs with high steady-state concentrations might be associated with greater risk reductions in cardiovascular and renal outcomes in patients with T2D. Long acting GLP-1RAs might outperform short acting ones in reducing the risk of cardiovascular outcomes. These findings provided new insights for guiding the clinical applications of GLP-1RAs in patients with T2D. [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]

Background: The consistency of cardiovascular risk reduction by antidiabetes medications across racial and ethnic groups remains unclear. The aim of this study was to analyze racial/ethnic patterns in the results of cardiovascular outcomes trials of antidiabetes medications in people with type 2 diabetes.Method: PubMed and Cochrane library databases were searched from the inception dates to December 2020. Cardiovascular outcome trials in type 2 diabetes that randomized participants to antidiabetes medication or control treatment and reported results by race/ethnic groups or region were included.Results: A total of 19 studies were included in this meta-analysis. Among White participants, treatment with antidiabetes medications significantly decreased the risk of composite cardiovascular outcomes when compared with placebo treatment (OR = 0.88, 95% CI 0.83-0.94, p < 0.05). Among Asian participants, antidiabetes medications also significantly decreased the risk of composite cardiovascular outcomes when compared with control treatment (OR = 0.80, 95% CI 0.74-0.86, p < 0.05). A similar pattern was found when analyzing the effects of antidiabetes medications vs. control treatment in other racial/ethnic groups comprising mostly Hispanics and Pacific Islanders (OR = 0.87, 95% CI 0.78-0.98, p < 0.05). However, among Black participants, treatment with antidiabetes medications resulted in nominal but non-significant decreases in the composite cardiovascular outcomes when compared with control treatment (OR = 0.84, 95% CI 0.62-1.14, p = 0.26).Conclusions: The present meta-analysis showed cardiovascular safety of antidiabetes medications in people with type 2 diabetes from all racial/ethnic groups studied; however, significant composite cardiovascular risk reductions were demonstrated only in White and Asian participants. To determine whether antidiabetes drugs confer consistent cardiovascular benefits in Black and other racial/ethnic participants requires more investigations in the future. [ABSTRACT FROM AUTHOR]