2.Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study.
Huan YU ; Ruo Tong YANG ; Si Yue WANG ; Jun Hui WU ; Meng Ying WANG ; Xue ying QIN ; Tao WU ; Da Fang CHEN ; Yi Qun WU ; Yong Hua HU
Journal of Peking University(Health Sciences) 2023;55(3):456-464
		                        		
		                        			OBJECTIVE:
		                        			To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.
		                        		
		                        			METHODS:
		                        			A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.
		                        		
		                        			RESULTS:
		                        			The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.
		                        		
		                        			CONCLUSION
		                        			Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Metformin/adverse effects*
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 2/drug therapy*
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Ischemic Stroke/complications*
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Hypoglycemic Agents/adverse effects*
		                        			;
		                        		
		                        			Stroke/prevention & control*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
3.Effect and Safety of Acupuncture for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of 21 Randomised Controlled Trials.
Shu-Qing LI ; Jian-Rong CHEN ; Mei-Lu LIU ; Yan-Ping WANG ; Xu ZHOU ; Xin SUN
Chinese journal of integrative medicine 2022;28(5):463-471
		                        		
		                        			OBJECTIVE:
		                        			To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM).
		                        		
		                        			METHODS:
		                        			PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.
		                        		
		                        			RESULTS:
		                        			Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD -6.46 mg/dL, 95% CI -11.95 to -0.98; moderate-quality evidence) and HOMA-IR (MD -1.23, 95% CI -2.16 to -0.31; low-quality evidence), but comparable changes in HbA1c (MD -0.39%, 95% CI -0.84 to 1.61; very-low-quality evidence), 2hBG (MD -4.99 mg/dL, 95% CI -20.74 to 10.76; low-quality evidence), and FINS (MD -1.32 µIU/mL, 95% CI -3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild.
		                        		
		                        			CONCLUSIONS
		                        			The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Trial registration No. CRD42018115639).
		                        		
		                        		
		                        		
		                        			Acupuncture Therapy/methods*
		                        			;
		                        		
		                        			Blood Glucose
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 2/drug therapy*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoglycemic Agents/adverse effects*
		                        			;
		                        		
		                        			Insulin Resistance
		                        			;
		                        		
		                        			Randomized Controlled Trials as Topic
		                        			
		                        		
		                        	
4.Phytochemicals of Periploca aphylla Dcne. ameliorated streptozotocin-induced diabetes in rat.
Umbreen RASHID ; Muhammad Rashid KHAN
Environmental Health and Preventive Medicine 2021;26(1):38-38
		                        		
		                        			BACKGROUND:
		                        			Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats.
		                        		
		                        			METHODS:
		                        			The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols.
		                        		
		                        			RESULTS:
		                        			HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide.
		                        		
		                        			CONCLUSION
		                        			The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.
		                        		
		                        		
		                        		
		                        			1-Butanol/chemistry*
		                        			;
		                        		
		                        			Administration, Oral
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Diabetes Mellitus, Experimental/drug therapy*
		                        			;
		                        		
		                        			Dose-Response Relationship, Drug
		                        			;
		                        		
		                        			Hypoglycemic Agents/chemistry*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Periploca/chemistry*
		                        			;
		                        		
		                        			Phytochemicals/chemistry*
		                        			;
		                        		
		                        			Plant Extracts/chemistry*
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Streptozocin/adverse effects*
		                        			
		                        		
		                        	
5.Metformin treatment of antipsychotic-induced dyslipidemia: analysis of two randomized, placebo-controlled trials.
Ye YANG ; Xiaoyi WANG ; Dongyu KANG ; Yujun LONG ; Jianjun OU ; Wenbin GUO ; Jingping ZHAO ; Renrong WU
Journal of Central South University(Medical Sciences) 2019;44(10):1128-1136
		                        		
		                        			
		                        			To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L 
(P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.
		                        		
		                        		
		                        		
		                        			Antipsychotic Agents
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			Blood Glucose
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 2
		                        			;
		                        		
		                        			Double-Blind Method
		                        			;
		                        		
		                        			Dyslipidemias
		                        			;
		                        		
		                        			chemically induced
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoglycemic Agents
		                        			;
		                        		
		                        			Metformin
		                        			;
		                        		
		                        			therapeutic use
		                        			
		                        		
		                        	
7.Signal Detection for Cardiovascular Adverse Events of DPP-4 Inhibitors Using the Korea Adverse Event Reporting System Database, 2008–2016
Hyemin YI ; Ji Ho LEE ; Ju Young SHIN
Yonsei Medical Journal 2019;60(2):200-207
		                        		
		                        			
		                        			PURPOSE: Cardiovascular adverse events (AEs) after use of dipeptidyl peptidase-4 (DPP4) inhibitors have been reported and suspected since the launch of DPP-4 inhibitors in 2006. However, few studies have investigated the association between cardiovascular AEs and DPP-4 inhibitors. The objective of this study is to detect the signals of cardiovascular AEs after use of DPP-4 inhibitors by analyzing the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). MATERIALS AND METHODS: Data on the use of oral antidiabetic drugs from 2008 to 2016 were extracted from KIDS-KD, and analyzed descriptively. Data mining was conducted by calculating three indices, which were proportional reporting ratios, reporting odds ratios, and information components, to detect signals from use of all oral antidiabetic drugs including DPP-4 inhibitors. Then, the suspected adverse drug reactions (ADRs) were confirmed by signal detection, and drug label information between the Korea Ministry of Food and Drug Safety and the U.S. Food and Drug Administration were compared. RESULTS: Cardiovascular AEs after taking DPP-4 inhibitors were detected in only three (1.0%) out of a total of 307 AE reports. Two of the three cardiovascular AEs were reported after using sitagliptin and one using gemiglipitin, but these were not statistically significant. CONCLUSION: Analysis of spontaneous ADR reports data on the use of DPP-4 inhibitors could not showed the association between DPP-4 inhibitors and cardiovascular AEs, due to a small number of cardiovascular AEs reports.
		                        		
		                        		
		                        		
		                        			Cardiovascular Diseases
		                        			;
		                        		
		                        			Data Mining
		                        			;
		                        		
		                        			Drug-Related Side Effects and Adverse Reactions
		                        			;
		                        		
		                        			Hypoglycemic Agents
		                        			;
		                        		
		                        			Korea
		                        			;
		                        		
		                        			Odds Ratio
		                        			;
		                        		
		                        			Pharmacovigilance
		                        			;
		                        		
		                        			Sitagliptin Phosphate
		                        			;
		                        		
		                        			United States Food and Drug Administration
		                        			
		                        		
		                        	
9.Can Fundus Fluorescein Angiography be Performed for Diabetic Patients on Oral Metformin?.
Chinese Medical Sciences Journal 2017;32(2):119-112
		                        		
		                        			
		                        			Metformin is a kind of biguanide hypoglycemic agent that has been widely used in patients with diabetes mellitus. In clinical practice, whether metformin should be stopped before Fundus fluorescein angiography (FFA) remains largely unclear. Some endocrinologists suggest stop metformin before FFA. However, ophthalmologists do not always adopt this opinion in their practice. This situation may lead to disputes between physicians and patients. This article analyzed contrast-induced nephropathy(CIN) and the related contrast agent, as well as the adverse reactions of fluorescein angiography. It pointed out that the discrepancy may be caused by misunderstanding of contrast agents used in FFA. For angiography using iodine contrast agent, metformin must be stopped because of the increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has been reported yet. Therefore, the authors believe FFA is safe for diabetic patients with oral metformin and it is unnecessary to stop metformin before the examination.
		                        		
		                        		
		                        		
		                        			Administration, Oral
		                        			;
		                        		
		                        			Contrast Media
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 2
		                        			;
		                        		
		                        			diagnostic imaging
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Diabetic Retinopathy
		                        			;
		                        		
		                        			diagnostic imaging
		                        			;
		                        		
		                        			Fluorescein Angiography
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoglycemic Agents
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Kidney Diseases
		                        			;
		                        		
		                        			chemically induced
		                        			;
		                        		
		                        			Metformin
		                        			;
		                        		
		                        			therapeutic use
		                        			
		                        		
		                        	
10.Efficacy and Safety of SGLT2 Inhibitors in Patients with Type 1 Diabetes: A Meta-analysis of Randomized Controlled Trials.
Yingying YANG ; Hui PAN ; Bo WANG ; Shi CHEN ; Huijuan ZHU
Chinese Medical Sciences Journal 2017;32(1):22-27
		                        		
		                        			
		                        			Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2 (SGLT2) inhibitor-SGLT2 inhibitors, in combination with insulin for type 1 diabetes mellitus (T1DM). Methods We searched Medline, Embase, and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration (FDA) data and ClinicalTrials (http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria: randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin (HbA1c) levels were between 7% and 12%. The SGLT2 inhibitors group was treated with SGLT2 inhibitors plus insulin, and the placebo group received placebo plus insulin treatment. The outcomes should include one of the following items: fasting blood glucose, HbA1c, glycosuria, or adverse effects. Data were analyzed by two physicians independently. The risk of bias was evaluated by using the Cochrane Collaboration's Risk of Bias tool and heterogeneity among studies was assessed using Chi-square test. Random effect model was used to analyze the treatment effects with Revman 5.3.Results Three trials including 178 patients were enrolled. As compared to the placebo group, SGLT2 inhibitor absolutely decreased fasting blood glucose [mean differences (MD) -2.47 mmol/L, 95% confidence interval (CI) -3.65 to -1.28, P<0.001] and insulin dosage (standardized MD -0.75 U, 95%CI -1.17 to -0.33, P<0.001). SGLT2 inhibitors could also increase the excretion of urine glucose (MD 131.09 g/24 h, 95%CI 91.79 to 170.39, P<0.001). There were no significant differences in the incidences of hyperglycemia [odds ratio (OR) 1.82, 95%CI 0.63 to 5.29, P=0.27], urinary tract infection (OR 0.95, 95%CI 0.19 to 4.85, P=0.95), genital tract infection (OR 0.27, 95%CI 0.01 to 7.19, P=0.43), and diabetic ketoacidosis (OR 6.03, 95%CI 0.27 to 135.99, P=0.26) between the two groups.Conclusion SGLT2 inhibitors combined with insulin might be an efficient and safe treatment modality for T1DM patients.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Blood Glucose
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 1
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Drug Therapy, Combination
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Fasting
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Glycated Hemoglobin A
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoglycemic Agents
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Insulin
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Randomized Controlled Trials as Topic
		                        			;
		                        		
		                        			Sodium-Glucose Transporter 2
		                        			;
		                        		
		                        			antagonists & inhibitors
		                        			
		                        		
		                        	
            
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