Cardiovascular outcomes of antidiabetic drugs

2021 ◽  
Vol 12 (3) ◽  
pp. 98-106
Author(s):  
Ranjit Kumar Nath ◽  
Neeraj Pandit ◽  
Ajay Raj ◽  
B.N Pandit ◽  
Vinod Kumar ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Microvascular Complications ◽  
Cardiovascular Outcomes ◽  
Antidiabetic Drugs ◽  
Atherosclerotic Cardiovascular Disease ◽  
The Us ◽  
Endothelial Dysfunctions ◽  
Glucose Reduction ◽  
Lipid Parameters

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Intensive blood glucose reduction with antidiabetic drugs significantly reduce microvascular complications but there is no strong evidence of reduction in cardiovascular (CV) events. In 2008, the US Food and Drug Administration (FDA) issued guidance to demonstrate cardiovascular safety of newer antidiabetic drugs in addition to reduction in blood glucose level. After which a number of CVOTs were conducted involving newer antidiabetic drugs. The newer drugs (e.g. GLP-1 RAs, SGLT2 inhibitors and DPP 4 inhibitors) might have potential effects on body weight, lipid parameters and blood pressure, as well as endothelial dysfunctions, inflammatory markers and oxidative stress. The current review summarizes the results of the main trials focused on the cardiovascular outcomes of traditional as well as newer antidiabetic drugs.

scholarly journals Impact of type 2 diabetes and microvascular complications on mortality and cardiovascular outcomes in a multiethnic Asian population

2021 ◽  
Vol 9 (1) ◽  
pp. e001413
Author(s):  
Jonathan Yap ◽  
Kamalesh Anbalakan ◽  
Wan Ting Tay ◽  
Daniel Ting ◽  
Carol Yim Cheung ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glycemic Control ◽  
Microvascular Complications ◽  
Population Based ◽  
Cardiovascular Outcomes ◽  
Microvascular Complication ◽  
The Impact ◽  
Hba1c Levels

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methodsThis was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.ResultsA total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p<0.001) and MACE (adjusted HR 1.64, 95% CI 1.39 to 1.93, p<0.001). In those with diabetes, higher HbA1c levels were associated with increased MACE rates (adjusted HR (per 1% increase) 1.18, 95% CI 1.11 to 1.26, p<0.001) but not mortality (p=0.115). Subjects with two microvascular complications had significantly higher mortality and MACE compared with those with only either microvascular complication (adjusted p<0.05) and no microvascular complication (adjusted p<0.05).ConclusionDiabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.

scholarly journals Dietary Intake and Type 2 Diabetes

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2177
Author(s):  
Omorogieva Ojo
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Dietary Intake ◽  
Diabetic Complications ◽  
Dietary Interventions ◽  
Factors Associated ◽  
Dietary Strategies ◽  
Lipid Parameters

This editorial aims to examine the risk factors associated with type 2 diabetes and to discuss the evidence relating to dietary strategies for managing people with this condition. It is clear from the evidence presented that a range of dietary interventions can provide useful approaches for managing people with type 2 diabetes, including the regulation of blood glucose and lipid parameters, and for reducing the risks of acute and chronic diabetic complications.

Renal Protective Effects of a Diet and Exercise Intervention in Type 2 Diabetic Rats

2015 ◽  
Vol 18 (1) ◽  
pp. 76-81 ◽  
Author(s):  
Hua Liang
Keyword(s):  
Blood Glucose ◽  
Exercise Intervention ◽  
Microvascular Complications ◽  
Kidney Tissue ◽  
Protective Effects ◽  
Lipid Levels ◽  
Diet And Exercise ◽  
Diet And Exercise Intervention ◽  
Group D

Purpose: Diabetic nephropathy (DN) is one of the most common diabetic microvascular complications. Inflammatory factors participate in each stage of DN, and nuclear factor (NF)-κB and monocyte chemoattractant protein-1(MCP-1) play important mediation roles. The purpose of this study was to investigate the renal protective effects of a diet and exercise intervention in a rat model of Type 2 diabetes mellitus (T2DM). Method: Control rats (Group A, n = 10) were fed a normal diet, while 30 rats were fed a high-glucose, high-fat diet and given an intraperitoneal injection of streptozocin to establish the T2DM model. Model rats ( n = 8 per group) were randomized into Groups B, C, and D. Groups C and D were treated with glibenclamide, and Group D received an 8-week diet and exercise intervention. Blood, 12-hr urine, and kidney tissue samples were collected postintervention for detecting blood glucose and lipid levels, expression of MCP-1 and NF-κB, and renal function indices. Results: Postintervention, blood glucose, and lipid levels in Groups C and D were lower than those in Group B, with decreases in Group D significantly greater than in Group C. Every index of renal protection showed greater improvement in Group D than in Group C ( p < .05). The expression of NF-κB and MCP-1 was lower in Group D than in Group C ( p < .05). Conclusions: The diet and exercise intervention reduced the inflammatory reaction and delayed T2DM and DN progression by inhibiting the activation of NF-κB and downregulating the expression of MCP-1.

scholarly journals Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261986
Author(s):  
Ning Li ◽  
Guowei Zhou ◽  
Yawei Zheng ◽  
Dan Lv ◽  
Xiangjun Zhu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Ejection Fraction ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Atherosclerotic Cardiovascular Disease ◽  
Reduced Ejection Fraction ◽  
Stage 4

Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR<30mL/min per 1.73m2) and underlying diseases (Type 2 diabetes, heart failure (Preserved ejection fraction or reduced ejection fraction), atherosclerotic cardiovascular disease) were used to stratify efficacy and safety outcomes. The results were subjected to a sensitivity analysis to ensure that they were reliable. Results In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

scholarly journals Decreased MicroRNA-150 Exacerbates Neuronal Apoptosis in the Diabetic Retina

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1135
Author(s):  
Fei Yu ◽  
Michael L. Ko ◽  
Gladys Y.-P. Ko
Keyword(s):  
Microvascular Complications ◽  
Diabetic Patients ◽  
Working Adults ◽  
Downstream Target ◽  
Diabetic Retina ◽  
The Us ◽  
Onset Of Diabetes ◽  
Ets Domain ◽  
Interfering Rna

Diabetic retinopathy (DR) is a chronic complication associated with diabetes and the number one cause of blindness in working adults in the US. More than 90% of diabetic patients have obesity-associated type 2 diabetes (T2D), and 60% of T2D patients will develop DR. Photoreceptors undergo apoptosis shortly after the onset of diabetes, which contributes to the retinal dysfunction and microvascular complications leading to vision impairment. However, how diabetic insults cause photoreceptor apoptosis remains unclear. In this study, obesity-associated T2D mice and cultured photoreceptors were used to investigate how decreased microRNA-150 (miR-150) and its downstream target were involved in photoreceptor apoptosis. In the T2D retina, miR-150 was decreased with its target ETS-domain transcription factor (ELK1) and phosphorylated ELK1 at threonine 417 (pELK1T417) upregulated. In cultured photoreceptors, treatments with palmitic acid (PA), to mimic a high-fat environment, decreased miR-150 but upregulated ELK1, pELK1T417, and the translocation of pELK1T417 from the cytoplasm to the cell nucleus. Deletion of miR-150 (miR-150−/−) exacerbates T2D- or PA-induced photoreceptor apoptosis. Blocking the expression of ELK1 with small interfering RNA (siRNA) for Elk1 did not rescue PA-induced photoreceptor apoptosis. Translocation of pELK1T417 from cytoplasm-to-nucleus appears to be the key step of diabetic insult-elicited photoreceptor apoptosis.

SGLT2 Inhibitors: A New Generation of Antidiabetic Drugs

2015 ◽  
Vol 8 (2) ◽  
pp. 2787-2798
Author(s):  
S.K Kulkarni ◽  
Madhavi Kuchana ◽  
D Samba Reddy
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Sglt2 Inhibitors ◽  
Antidiabetic Drugs ◽  
New Drugs ◽  
Hypoglycemic Agents ◽  
Great Promise ◽  
Glucose Levels ◽  
Blood Glucose Levels

The incidence of type 2 diabetes is markedly increasing worldwide. Despite a plethora of therapeutic options available for the treatment of type 2 diabetes, the ability to effectively normalize blood glucose levels and prevent    long-term complications of diabetes remains elusive. There is intense search for new drugs for diabetes.  One novel therapeutic class of antidiabetic drugs is sodium-glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 is renal membrane transporter that plays an important role in glucose reabsorption within kidneys. Hence, inhibition of SGLT2 enhances renal glucose excretion, consequently lowers blood glucose levels in an insulin- independent manner. This article describes various SGLT2 inhibitors currently available in the market and also agents that are undergoing clinical trials for the treatment of type 2 diabetes. Currently three SGLT2 inhibitors are approved for clinical use and several others are still in development. The emerging data suggest that SGLT2 inhibitors hold great promise for the clinical management of type 2 diabetes. It remains to be seen whether this class of drugs offers additional advantages over the existing oral hypoglycemic agents.

scholarly journals A randomized, double-blind, placebo-controlled trial to evaluate the hypoglycemic efficacy of the mcIRBP-19-containing Momordica charantia L. fruit extracts in the type 2 diabetic subjects

2022 ◽  
Author(s):  
Yi-Sun Yang ◽  
Nian-Yi Wu ◽  
Edy Kornelius ◽  
Chien-Ning Huang ◽  
Nae-Cherng Yang
Keyword(s):  
Blood Glucose ◽  
Animal Studies ◽  
Controlled Trial ◽  
Fasting Blood Glucose ◽  
Momordica Charantia ◽  
Antidiabetic Drugs ◽  
Bitter Gourd ◽  
Double Blind

Background: The fruits of Momordica charantia L., also named as bitter gourd or bitter melon in popular, is a common tropical vegetable that is traditionally used to reduce blood glucose. A peptide derived from bitter gourd, Momordica charantia insulin receptor binding peptid-19 (mcIRBP-19), had been demonstrated to possess an insulin-like effect in vitro and in the animal studies. However, the benefit of the mcIRBP-19-containing bitter gourd extracts (mcIRBP-19-BGE) for lowering blood glucose levels in humans is unknown. Objective: This aim of this study was to evaluate the hypoglycemic efficacy of mcIRBP-19-BGE in subjects with type 2 diabetes who had taken antidiabetic medications but failed to achieve the treatment goal. Whether glucose lowering efficacy of mcIRBP-19-BGE could be demonstrated when the antidiabetic medications were ineffective was also studied. Design: Subjects were randomly assigned to two groups: mcIRBP-19-BGE treatment group (N = 20) and placebo group (N = 20), and were orally administered 600 mg/day investigational product or placebo for 3 months. Subjects whose hemoglobin A1c (HbA1c) continued declining before the trial initiation with the antidiabetic drugs were excluded from the subset analysis to further investigate the efficacy for those who failed to respond to the antidiabetic medications. Results: The oral administration of mcIRBP-19-BGE decreased with a borderline significance at fasting blood glucose (FBG; P = 0.057) and HbA1c (P = 0.060). The subgroup analysis (N = 29) showed that mcIRBP-19-BGE had a significant effect on reducing FBG (from 172.5 ± 32.6 mg/dL to 159.4 ± 18.3 mg/dL, P = 0.041) and HbA1c (from 8.0 ± 0.7% to 7.5 ± 0.8%, P = 0.010). Conclusion: All of these results demonstrate that mcIRBP-19-BGE possesses a hypoglycemic effect, and can have a significant reduction in FBG and HbA1c when the antidiabetic drugs are ineffective.

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