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Efficacy and safety of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as monotherapy or add-on to metformin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

第一作者:Wang, ZY

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

AimsTo compare the efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) as monotherapy or add-on to metformin (Met) in patients with type 2 diabetes mellitus (T2DM). Materials and Methods PubMed, Embase and sites were systematically searched for randomized controlled trials to assess the efficacy and safety of DPP-4is and SGLT-2is in patients with T2DM. Risk ratio (RR) and weighted mean difference (WMD) were used to evaluate outcomes. ResultsIn the analysis of 25 randomized trials, which involved 14619 patients, SGLT-2is were associated with a significantly stronger reduction in haemoglobin A1c (HbA1c) (WMD 0.13%, 95% credible interval [CI], 0.04%-0.22%, P=.005) and fasting plasma glucose (FPG) (WMD 0.80mmol/L, 95% CI, 0.58-1.01mmol/L, P<.00001) than were DPP-4is. However, no significant difference between the 2 drug categories was found in the risk of hypoglycaemic events (RR, 0.99; 95% CI, 0.78-1.26, P=.92). SGLT-2is plus Met was associated with a more significant decrease in FPG (WMD 0.71mmol/L, 95% CI, 0.43-1.00mmol/L, P<.00001) than was DPP-4is plus Met. However, no differences were found in the reduction of HbA1c (WMD 0.11%, 95% CI, -0.03%-0.25%, P=.12) or the risk of hypoglycaemic events (RR, 1.02; 95% CI, 0.80-1.31, P=.86). ConclusionsThis review revealed that, compared to DPP-4is, SGLT-2is significantly reduced HbA1c, FPG and body weight without increasing the risk of hypoglycaemia in diabetes treatment.

IF:6.13

Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta-analysis of randomized controlled trials

第一作者:Zhao, YM

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

The aim of this study was to describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, CENTRAL, EMBASE and ClinicalTrials.gov were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to May 20, 2017. A total of 62 studies, comprising 34 941 patients, were included. Any of the SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total weighted mean difference [WMD] -37.73 mu mol/L, 95% CI [-40.51, -34.95]). Treatment with empagliflozin resulted in a superior reduction in SUA (WMD -45.83 mu mol/L, 95% CI [-53.03, -38.63]). The effect persisted during long-term treatment. Dapagliflozin decreased SUA in a dose-dependent manner (from 5 to 50 mg, P = .014). In subgroup analyses, greater reductions could be observed during the course of early diabetes and the SUA-lowering effect was abolished in patients with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m(2)). The effect of SGLT2 inhibitors on SUA reduction suggests that this class of drugs might be beneficial for diabetic patients with hyperuricaemia.

IF:6.13

Efficacy and safety of lixisenatide in a predominantly Asian population with type 2 diabetes insufficiently controlled with basal insulin: The GetGoal-L-C randomized trial

第一作者:Yang, WY

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

AimsTo assess the effects on glycaemic control of lixisenatide vs placebo as add-on treatment to basal insulin (BI)metformin and effects on glycated haemoglobin (HbA1c) reduction in patients with insufficiently controlled type 2 diabetes (T2D). MethodsPatients (n=448) with inadequately controlled T2D were randomized (1:1) to lixisenatide or placebo as add-on to BImetformin for 24weeks after an 8-week run-in phase, during which BI was titrated to a target self-monitored plasma glucose (SMPG; 4.4-5.6mmol/L). The primary endpoint was absolute change in HbA1c from baseline to week 24. Secondary efficacy endpoints included: percentage of responders; changes in 2-hour postprandial plasma glucose (PPG); 7-point SMPG (daily average); body weight (BW); total daily BI dose; fasting plasma glucose; and safety assessments. ResultsBaseline demographics were similar in the two treatment groups. After insulin optimization during run-in, lixisenatide was superior to placebo in mean change from baseline (7.9% [standard deviation {s.d.}, 0.66] and 7.9% [0.70], respectively) to week 24 in HbA1c (least squares mean [standard error {s.e.}] change -0.62% [0.09] vs -0.11% [0.09]; P<.0001, respectively) and higher proportions of patients achieved HbA1c targets. Two-hour PPG, daily mean SMPG and mean BW were reduced further and daily BI dose was lower with lixisenatide than placebo (-1.12kg vs 0.04kg [P<.0001]; -3.0U vs -1.9U [P=.0033], respectively). Treatment-emergent adverse events were greater with lixisenatide than placebo (63.8% vs 40.8%, respectively). The incidence of symptomatic hypoglycaemia was similar (lixisenatide 15.6% vs placebo 13.5%). ConclusionsIn Asian patients insufficiently controlled on BI +/- metformin, lixisenatide was superior to placebo in glycaemic control, with a tolerability profile in line with other glucagon-like peptide-1 receptor agonists.

IF:6.13

Development of a cardiovascular diseases risk prediction model and tools for Chinese patients with type 2 diabetes mellitus: A population-based retrospective cohort study

第一作者:Wan, EYF

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

AimsEvidence-based cardiovascular diseases (CVD) risk prediction models and tools specific for Chinese patients with type 2 diabetes mellitus (T2DM) are currently unavailable. This study aimed to develop and validate a CVD risk prediction model for Chinese T2DM patients. MethodsA retrospective cohort study was conducted with 137935 Chinese patients aged 18 to 79years with T2DM and without prior history of CVD, who had received public primary care services between January 1, 2010 and December 31, 2010. Using the derivation cohort over a median follow-up of 5years, the interaction effect between predictors and age were derived using Cox proportional hazards regression with a forward stepwise approach. Harrell's C statistic and calibration plot were used on the validation cohort to assess the discrimination and calibration of the models. The web calculator and chart were developed based on the developed models. ResultsFor both genders, predictors for higher risk of CVD were older age, smoking, longer diabetes duration, usage of anti-hypertensive drug and insulin, higher body mass index, haemoglobin A1c (HbA1c), systolic and diastolic blood pressure, a total cholesterol to high-density lipoprotein-cholesterol (TC/HDL-C) ratio and urine albumin to creatinine ratio, and lower estimated glomerular filtration rate. Interaction factors with age demonstrated a greater weighting of TC/HDL-C ratio in both younger females and males, and smoking status and HbA1c in younger males. ConclusionThe developed models, translated into a web calculator and color-coded chart, served as evidence-based visual aids that facilitate clinicians to estimate quickly the 5-year CVD risk for Chinese T2DM patients and to guide intervention.

IF:6.13

Different intervention strategies for preventing type 2 diabetes mellitus in China: A systematic review and network meta-analysis of randomized controlled trials

第一作者:Pang, B

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

Different strategies are increasingly used for early intervention in prediabetes in China, but the effects of these strategies on incident diabetes have not yet been confirmed. The aim of the present study was to assess systematically the effects of different strategies for preventing diabetes, aimed at Chinese people with prediabetes. Seven electronic databases were searched to identify eligible trials published from inception to September 20, 2016. Randomized controlled trials with a minimum follow-up duration of 6months were included. Standard pairwise meta-analysis with a random-effects model and network meta-analysis with a frequentist framework were performed. A total of 63 studies, including 11 intervention strategies, were included. Compared with placebo, all strategies, except for lipid-affecting drugs and sitagliptin, reduced the rate of incident diabetes with different levels of effectiveness, ranging from 0.18 (95% confidence interval [CI] 0.12, 0.27) to 0.39 (95% CI 0.20, 0.75). Ranking probability analysis indicated that metformin and -cell-stimulating drugs reduced the risk of diabetes most, with probabilities of 87.4% and 81%, respectively. Ethnicity and cultural factors should be considered for diabetes prevention. Most of the included trials were of poor methodological quality, however, and the results should be interpreted with caution.

IF:6.13

Na+/H+ exchanger 3 blockade ameliorates type 2 diabetes mellitus via inhibition of sodium-glucose co-transporter 1-mediated glucose absorption in the small intestine

第一作者:Chan, LKY

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

AimTo elucidate the role of Na+/H+ exchanger 3 (NHE3) in sodium-glucose co-transporter 1 (SGLT1)-mediated small intestinal brush border membrane (BBM) glucose absorption and its functional implications in type 2 diabetes mellitus (T2DM). Materials and MethodsHuman jejunal samples were obtained from patients undergoing gastrectomy. C-14-glucose absorption was measured by liquid scintillation counting. NHE3 expression was suppressed by siRNA-mediated knockdown or augmented in Caco2 cells. Glucose and insulin tolerance in db/db and m+/db mice was assessed with oral and intraperitoneal glucose tolerance tests, and an intraperitoneal insulin tolerance test. Insulin resistance and -cell function were assessed using homeostatic model assessment of insulin resistance and -cell function. ResultsNHE3 expression was upregulated in db/db mouse jejunal BBM and high-glucose-treated Caco2 cells. NHE3 blockade impaired SGLT1-mediated glucose absorption in human jejunum, m+/db and db/db mouse jejunums, and Caco2 cells, via serum/glucocorticoid-regulated kinase 1 (SGK1). NHE3 knockdown suppressed SGLT1-mediated glucose uptake and reduced mRNA and protein levels of SGK1 and SGLT1, which were conversely enhanced by NHE3 overexpression. Chronic S3226 treatment diminished postprandial glucose levels and ameliorated glucose intolerance in db/db mice. ConclusionNHE3 is essential in the modulation of small intestinal BBM glucose absorption. Our findings provide a rationale for future possible clinical application of NHE3 for treatment of T2DM through reducing intestinal glucose uptake and counteracting postprandial hyperglycaemia.

IF:6.13

Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: Results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial

第一作者:Dou, JT

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

AimTo assess the efficacy and safety of saxagliptin plus metformin over 24weeks in pharmacotherapy-naive Chinese patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA1c, 8.0%-12.0%). Research Design and MethodsIn this multicentre, double-blind, active-controlled study (The START study: NCT02273050, ), patients were randomized (1:1:1) to saxagliptin 5mg plus metformin, saxagliptin 5mg plus placebo or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500mg to a maximum of 2000mg/d over 8weeks. The primary end point was change in HbA1c from baseline to Week 24. ResultsData from 630 patients (66.5% men; mean age, 50.1years; mean body mass index, 26.6kg/m(2); mean HbA1c, 9.4%; mean diabetes duration, 0.81years) were analysed. Mean reduction in HbA1c was greater with saxagliptin plus metformin (-3.0%) than with saxagliptin plus placebo (-2.1%; P<.001) or metformin plus placebo (-2.8%; P=.034). Changes in mean fasting plasma glucose, 120-minute postprandial glucose, and 180-minute postprandial glucose area under the curve were greater, and more patients achieved a therapeutic glycaemic response, with saxagliptin plus metformin than with either monotherapy. Hypoglycaemic events were infrequent (<2%). Incidence of adverse events was similar among groups; upper respiratory tract infection and diarrhoea were most common. ConclusionsSaxagliptin 5mg plus metformin significantly improved glycaemic control compared with either monotherapy in treatment-naive Chinese patients with type 2 diabetes, and was well tolerated.

IF:6.13

Saxagliptin add-on therapy in Chinese patients with type 2 diabetes inadequately controlled by insulin with or without metformin: Results from the SUPER study, a randomized, double-blind, placebo-controlled trial

第一作者:Chen, YL

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

This prospective, multicentre, phase III study (NCT02104804) evaluated the efficacy and safety of saxagliptin add-on therapy in Chinese patients with type 2 diabetes inadequately controlled by insulin +/- metformin. Patients with glycated haemoglobin (HbA1c) 7.5% to 10.5% and fasting plasma glucose (FPG) <15 mmol/L (270mg/dL) on stable insulin therapy (20-150U/d) were randomized (1:1) to saxagliptin 5 mg once daily (N=232) or placebo (N=230) for 24weeks, stratified by metformin use. The primary efficacy measure was change in HbA1c. Saxagliptin treatment resulted in a greater adjusted mean change in HbA1c from baseline to week 24 than placebo (-0.58%; P<.001), irrespective of metformin use, and a greater mean change in FPG (0.9 mmol/L [-15.9 mg/dL]; P<.001). More patients achieved HbA1c <7% with saxagliptin (11.4%) than with placebo (3.5%, P=.002). Adverse events and incidence of hypoglycaemia were similar in both groups. Overall, add-on saxagliptin 5 mg once daily significantly improved glycaemic control without increasing hypoglycaemia risk and was well tolerated in Chinese patients with type 2 diabetes inadequately controlled by insulin (+/- metformin).

IF:6.13

Direct head-to-head comparison of glycaemic durability of dipeptidyl peptidase-4 inhibitors and sulphonylureas in patients with type 2 diabetes mellitus: A meta-analysis of long-term randomized controlled trials

第一作者:Chen, K

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

We performed a meta-analysis of randomized controlled trials (RCTs) to compare the long-term glycaemic durability of dipeptidyl-peptidase 4 (DPP-4) inhibitors vs that of sulphonylureas (SUs) in patients with type 2 diabetes mellitus (T2DM), in terms of the changes in glycated haemoglobin (HbA1c) levels from an intermediate time point (26 or 52 weeks) to 104 weeks of treatment. The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant RCTs. Eight RCTs were included. Compared with SUs, DPP-4 inhibitors were associated with significantly smaller increases in the HbA1c level from 24 to 28 weeks to 104 weeks (mean difference [MD]: -0.16%, 95% confidence interval [CI]: -0.21 to -0.11; P<.001) and from 52 weeks to 104 weeks (MD -0.06%, 95% CI -0.10 to -0.02; P=.001). No significant heterogeneities were detected among the included comparisons (I-2=0%). These results suggest that long-term treatment with DPP-4 inhibitors confers better durability of glycaemic response than treatment with SUs in patients with T2DM, which may indicate that DPP-4 inhibitors better preserve islet beta-cell function compared with SUs.

IF:6.13

Anti-interleukin-1 therapy has mild hypoglycaemic effect in type 2 diabetes

第一作者:Huang, JY

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

The aim of this study was to systematically evaluate the efficacy and safety of anti-interleukin-1 therapy for type 2 diabetes. A literature search of PubMed and Embase for available trials on anti-interleukin-1 therapy in type 2 diabetes was performed. The baseline characteristics, changes in HbA1c and other metabolic parameters, and adverse events were extracted from included randomized controlled trials (RCTs) and were analysed with Review Manager. Mean differences (MDs) and 95% confidence intervals (Cis) were calculated to measure differences in metabolic parameters. Odds ratio and 95% CIs were calculated for adverse event rates. Five RCTs were included in the current meta-analysis with 357 subjects undergoing anti-interleukin-1 therapy (IL-1 receptor antagonist or anti-IL-1beta antibody) and 221 controls who received placebo. The HbA1c decrement (%) of anti-interleukin-1 group was significantly higher than that of the placebo group (MD=0.23; 95% CI, -0.39 to -0.07; P=.005). AUC of C-peptide was improved also (MD=14.55; 95% CI, 1.81-27.28; P=.03) after anti-interleukin-1 intervention. There was no difference in the rate of adverse events (odds ratio,1.16; 95% CI, 0.90-1.49; P=.25) between 2 groups. Anti-interleukin-1 therapy has mild hypoglycaemic effect in type 2 diabetes.

IF:6.13

Comparative effectiveness of metformin monotherapy in extended release and immediate release formulations for the treatment of type 2 diabetes in treatment-naive Chinese patients: Analysis of results from the CONSENT trial

第一作者:Ji, LN

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

Aims: Metformin treatment for type 2 diabetes mellitus (T2DM) can be limited by gastrointestinal (GI) adverse events (AEs), resulting in treatment discontinuation. We investigated whether once-daily metformin extended release (XR) is superior in terms of GI tolerability, with non-inferior efficacy, compared with thrice-daily metformin immediate release (IR) in treatment-naive Chinese patients with T2DM. Materials and Methods: This prospective, open-label, randomized, multicentre, phase IV interventional study enrolled Chinese T2DM patients to receive either metformin XR or metformin IR with a 2-week screening period, a 16-week treatment period and a 2-week follow-up period without treatment. Co-primary endpoints were a non-inferiority assessment of metformin XR vs metformin IR in glycated haemoglobin (HbA1c) least squares mean (LSM) change from baseline to week 16 and the superiority of GI tolerability for metformin XR vs metformin IR. Results: Overall, 532 patients were randomized to metformin IR (n=267) or metformin XR (n=265). The HbA1c LSM change was -1.61% and -1.58% in each group, respectively (LSM difference, 0.03; 95% confidence interval [CI], -0.10, 0.17). Incidences of drug-related AEs were 26.5% (n=66) in the metformin IR-only group and 32.2% (n=85) in the metformin XR-only group, and GI AEs were 23.8% and 22.3% in each group, respectively (difference, -1.52; 95% CI, -8.60, 5.56). The treatment difference met the predefined non-inferiority upper CI margin of 0.4% in HbA1c. Conclusions: Metformin XR was non-inferior to metformin IR for the LSM change in HbA1c from baseline to week 16 and not superior to metformin IR for overall GI AE incidence during treatment of Chinese T2DM patients.

IF:6.13

Incretin-based therapies and risk of pancreatic cancer in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

第一作者:Wang, HN

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

Aims: To perform a meta-analysis of randomized controlled trials (RCTs), including 6 recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with type 2 diabetes (T2DM). Materials and Methods: For the period January 1, 2007 to May 1, 2017, the PubMed, Embase, Cochrane Central Register and databases were searched for RCTs in people with T2DM that compared incretin drugs with placebo or other antidiabetic drugs, with treatment and follow-up durations of >= 52 weeks. Two reviewers screened the studies, extracted the data and assessed the risk of bias independently and in duplicate. Results: A total of 33 studies (n = 79971), including the 6 CVOTs, with 87 pancreatic cancer events were identified. Overall, the pancreatic cancer risk was not increased in patients administered incretin drugs compared with controls (Peto odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.02). In the 6 CVOTs, 79 pancreatic cancer events were identified in 55248 participants. Pooled estimates of the 6 CVOTs showed an identical tendency (Peto OR 0.65, 95% CI 0.42-1.01). Notably, in the subgroup of participants who received treatment and follow-up for >= 104 weeks, 84 pancreatic cancer events were identified in 59919 participants, and a lower risk of pancreatic cancer was associated with incretin-based therapies (Peto OR 0.62, 95% CI 0.41-0.95). Conclusions: Treatment with incretin drugs was not associated with an increased risk of pancreatic cancer in people with T2DM. Instead, it might protect against pancreatic malignancy in patients treated for 104 weeks.

IF:6.13

A randomized, open-label, multicentre, parallel-controlled study comparing the efficacy and safety of biphasic insulin aspart 30 plus metformin with biphasic insulin aspart 30 monotherapy for type 2 diabetes patients inadequately controlled with oral anti

第一作者:Guo, LX

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

Aim Materials and methods To confirm non-inferiority of biphasic insulin aspart 30 (BIAsp 30) plus metformin to BIAsp 30 in lowering glycated haemoglobin (HbA1c) in Chinese patients with inadequately controlled type 2 diabetes using oral antidiabetic drugs. In this 16-week, prospective, randomized, open-label, multicentre, parallel-controlled study, patients aged 18-79 years with HbA1c >= 7% were randomized to BIAsp 30 plus metformin (n = 130) or BIAsp 30 (n = 127). Initially, 500 mg metformin was administered twice daily and BIAsp 30 was administered at 0.2-0.3 U/kg/d. Changes in HbA1c % from baseline to week 16 as well as secondary and safety endpoints were assessed. Results Conclusion In total, 83.66% of patients in the BIAsp 30 plus metformin (n = 110) and the BIAsp 30 (n = 105) groups completed the study. Mean (+/- standard deviation) change in HbA1c from baseline to endpoint was -1.74 +/- 1.64% and -1.32 +/- 2.05% with BIAsp 30 plus metformin and BIAsp 30, respectively. Least squares mean treatment difference was -0.67% (95% CI, -1.06; -0.28). The upper limit of the 95% CI was <0.4 (non-inferiority margin). A significantly higher proportion of individuals reached HbA1c <7% with BIAsp 30 plus metformin than with BIAsp 30 (53.15% vs 35.19%; P = 0.0074). At endpoint, daily BIAsp 30 dose (P < 0.001) and weight gain were significantly lower (P < 0.05) in the BIAsp 30 plus metformin group compared with the BIAsp 30 group. No between-group differences in number of hypoglycaemic events were observed. BIAsp 30 plus metformin was non-inferior to BIAsp 30 in safely reducing HbA1c in this study.

IF:6.13

Effects of the interaction between glycated haemoglobin genetic risk score and postpartum weight reduction on glycaemic changes: A gene-weight interaction analysis

第一作者:Han, LY

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

Aim Methods To investigate the effects of the interaction between glycated haemoglobin (HbA1c) genetic risk score and weight changes during and after pregnancy (postpartum weight reduction and gestational weight gain) on long-term glycaemic changes in the largest cohort of women with a history of gestational diabetes mellitus (GDM). This was a retrospective cohort using the baseline data from the Tianjin Gestational Diabetes Mellitus Prevention Programme. A genetic risk score was established by combining 10 HbA1c-related single-nucleotide polymorphisms, which were identified by genome-wide association studies. General linear regression models were applied to evaluate the effect of interaction between HbA1c genetic risk score and weight changes during and after pregnancy (postpartum weight reduction and gestational weight gain) on glycaemic changes. Results Conclusions 'A total of 1156 women with a history of GDM were included in this respective cohort study. Statistical differences in pre-pregnancy weight, pre-delivery weight and postpartum weight were evidenced across different groups of postpartum weight reduction. After adjusting for covariates, statistical significance for changes in HbA1c level was only observed in the postpartum weight reduction <5 kg/y group (P = 0.002), and a significant effect of interaction between HbA1c genetic risk score and postpartum weight reduction on long-term changes in HbA1c was evidenced (P interaction = 0.01). In women with postpartum weight reduction >= 8 kg/y, those with a lower HbA1c genetic risk score had a greater decrease in HbA1c level. HbA1c genetic risk score interacts with postpartum weight reduction to affect long-term changes in HbA1c levels among women with a history of GDM.

IF:6.13

Comparisons of diabetic retinopathy events associated with glucose-lowering drugs in patients with type 2 diabetes mellitus: A network meta-analysis

第一作者:Tang, HL

期刊: DIABETES OBESITY & METABOLISM, 2018; 20 (无)

Aim: To assess the comparative effects of glucose-lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random-effects pairwise and network meta-analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 37 independent RCTs with 1806 DR events among 100 928 patients with T2DM were included. The mean duration of diabetes was 8.7 years and mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta-analysis found that DPP-4i (OR, 1.20; 95% CI, 0.87-1.65), GLP-1RA (OR, 1.19; 95% CI, 0.94-1.52) and SGLT2 inhibitors (OR, 0.79; 95% CI, 0.49-1.28) were not associated with a higher risk of DR than placebo; however, a significantly increased risk of DR was associated with DPP-4i in the pairwise meta-analysis (OR, 1.27; 95% CI, 1.05-1.53). Sulfonylureas, on the other hand, were associated with a significantly increased risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01-2.76). Conclusions: Current evidence indicates that the association between DPP-4i, GLP-1RA or SGLT2 inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence suggests that sulfonylureas may be associated with increased risk of DR. However, given that DR events were not systematically assessed, these effects should be explored further in largescale, well-designed studies.

IF:6.13

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