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Cardiovascular Protection with Anti-hyperglycemic Agents
AbstractDiabetes mellitus is a major risk factor for cardiovascular (CV) disease. Conversely, CV disease is responsible for a majority of the deaths in patients with diabetes. Many drug trials have concentrated on blood glucose (hemoglobin A1c) reduction. This strategy, while reducing microvascular outcomes like nephropathy and neuropathy, has little or no effect on reducing macrovascular events like heart attack, stroke, and heart failure. It has been postulated that hypoglycemia may counterbalance some of the beneficial effects of anti-hyperglycemic agents, but this is not proven. Further, trial evidence for thiazolidine...
Source: American Journal of Cardiovascular Drugs - February 15, 2019 Category: Cardiology Source Type: research

Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study
Conclusion: We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.
Source: Journal of Hypertension - January 17, 2019 Category: Cardiology Tags: ORIGINAL PAPERS: Vessels Source Type: research

Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.
CONCLUSIONS: AGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events. PMID: 30592787 [PubMed - as supplied by publisher]
Source: Cochrane Database of Systematic Reviews - December 28, 2018 Category: General Medicine Authors: Moelands SV, Lucassen PL, Akkermans RP, De Grauw WJ, Van de Laar FA Tags: Cochrane Database Syst Rev Source Type: research

Use of liraglutide and risk of major cardiovascular events: a register-based cohort study in Denmark and Sweden
Publication date: Available online 5 December 2018Source: The Lancet Diabetes & EndocrinologyAuthor(s): Henrik Svanström, Peter Ueda, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn PasternakSummaryBackgroundTrial evidence shows that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduces the risk of major cardiovascular events among patients with type 2 diabetes who have established cardiovascular disease or are at high cardiovascular risk. We aimed to assess the cardiovascular effectiveness of liraglutide in rou...
Source: The Lancet Diabetes and Endocrinology - December 6, 2018 Category: Endocrinology Source Type: research

The Impact of Metformin Use on the Cardiovascular Effects of DPP ‐4 Inhibitors: an Analysis of Medicare Claims Data 2007‐2015
ConclusionsIncidence rate differences in multiple cardiovascular outcomes appeared more favorable when DPP ‐4i initiation occurred in the presence of metformin, suggesting a possible interaction between DPP‐4i and metformin.This article is protected by copyright. All rights reserved.
Source: Diabetes, Obesity and Metabolism - November 20, 2018 Category: Endocrinology Authors: Matthew J. Crowley, Mugdha Gokhale, Virginia Pate, Til St ürmer, John B. Buse Tags: ORIGINAL ARTICLE Source Type: research

Cellular stress and AMPK activation as a common mechanism of action linking the effects of metformin and diverse compounds that alleviate accelerated aging defects in Hutchinson-Gilford progeria syndrome
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by an accelerated aging phenotype that typically leads to death via stroke or myocardial infarction at approximately 14.6  years of age. Most cases of HGPS have been linked to the extensive use of a cryptic splice donor site located in the LMNA gene due to a de novo mutation, generating a truncated and toxic protein known as progerin. Progerin accumulation in the nuclear membrane and within the nucleus distorts the n uclear architecture and negatively effects nuclear processes including DNA replication and repair, leading to accelerated ...
Source: Medical Hypotheses - July 2, 2018 Category: Biomedical Science Authors: Jahahreeh Finley Source Type: research

Combination of SGLT-2 inhibitors and GLP-1 receptor agonists: potential benefits in surrogate and hard endpoints.
CONCLUSION: The combination of metformin with SGLT2i, GLP-1 RA, and a potent statin, in high CVD risk patients with DM, is expected to substantially reduce CVD mortality and morbidity, improving the quality of life of patients with DM at the same time. Prospective studies are needed to confirm this finding. PMID: 29865997 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Design - June 3, 2018 Category: Drugs & Pharmacology Authors: Doumas M, Imprialos Κ, Stavropoulos K, Reklou A, Sachinidis A, Athyros VG Tags: Curr Pharm Des Source Type: research

The cardiovascular effect of incretin-based therapies among type 2 diabetes: a systematic review and network meta-analysis.
CONCLUSIONS: Incretin-based therapies show similar cardiovascular risk in comparison with metformin, insulin, thiazolidinediones, alpha-glucosidase inhibitor and sodium-glucose co-transporter 2. GLP-1RA could decrease the risk compared with sulfonylurea or placebo, while DPP-4I appears to have neutral effect on cardiovascular risk. PMID: 29320889 [PubMed - as supplied by publisher]
Source: Expert Opinion on Drug Safety - January 13, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Drug Saf Source Type: research

Can we go beyond surrogates?
Two years ago, data presented at the annual American Diabetes Association (ADA) meeting in New Orleans showed a marked decrease in deaths, especially those due to cardiovascular disease, with the use of empagliflozin. Two major questions have been asked: (i) was the result a fluke; and (ii) was it a class effect, or was it specific to the agent used? The hope that both questions would be answered by a second study has been answered: the conclusions of EMPA‐REG were not an anomaly and it is a class effect, not one caused by a specific drug. Importantly, do these studies require us to alter our algorithms for the treatment...
Source: Journal of Diabetes - October 19, 2017 Category: Endocrinology Authors: Andrew Drexler Tags: Editorial Source Type: research

Vitamin B12 Deficiency: Recognition and Management.
Abstract Vitamin B12 deficiency is a common cause of megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations. Screening average-risk adults for vitamin B12 deficiency is not recommended. Screening may be warranted in patients with one or more risk factors, such as gastric or small intestine resections, inflammatory bowel disease, use of metformin for more than four months, use of proton pump inhibitors or histamine H2 blockers for more than 12 months, vegans or strict vegetarians, and adults older than 75 years. Initial laboratory assessment should include a complete blood count ...
Source: American Family Physician - September 15, 2017 Category: Primary Care Authors: Langan RC, Goodbred AJ Tags: Am Fam Physician Source Type: research

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial
This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-yea...
Source: The Lancet Diabetes and Endocrinology - September 14, 2017 Category: Endocrinology Source Type: research

Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes
Conclusions/interpretationThere remains uncertainty about whether metformin reduces risk of cardiovascular disease among patients with type 2 diabetes, for whom it is the recommended first-line drug. Although this is mainly due to absence of evidence, it is unlikely that a definitive placebo-controlled cardiovascular endpoint trial among people with diabetes will be forthcoming. Alternative approaches to reduce the uncertainty include the use of electronic health records in long-term pragmatic evaluations, inclusion of metformin in factorial trials, publication of cardiovascular outcome data from adverse event reporting in...
Source: Diabetologia - August 2, 2017 Category: Endocrinology Source Type: research

Cardiovascular benefits and safety of non-insulin medications used in the treatment of type 2 diabetes mellitus.
Authors: Yandrapalli S, Jolly G, Horblitt A, Sanaani A, Aronow WS Abstract Diabetes mellitus is a growing in exponential proportions. If the current growth trend continues, it may result in every third adult in the United States having diabetes mellitus by 2050, and every 10(th) adult worldwide. Type 2 diabetes mellitus (T2DM) confers a 2- to 3-fold increased risk of cardiovascular (CV) events compared with non-diabetic patients, and CV mortality is responsible for around 80% mortality in this population. Patients with T2DM can have other features of insulin resistance-metabolic syndrome like hypertension, lipid ab...
Source: Postgraduate Medicine - July 29, 2017 Category: Internal Medicine Tags: Postgrad Med Source Type: research

Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators
CONCLUSIONS A large initial HbA1c reduction and achievement of low HbA1c levels within 6 months after metformin initiation are associated with a lower risk of cardiovascular events and death in patients with type 2 diabetes.
Source: Diabetes Care - May 22, 2017 Category: Endocrinology Authors: Svensson, E.; Baggesen, L. M.; Johnsen, S. P.; Pedersen, L.; Norrelund, H.; Buhl, E. S.; Haase, C. L.; Thomsen, R. W. Tags: Cardiovascular and Metabolic Risk Source Type: research

Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus.
CONCLUSIONS: There is no firm evidence that DPP-4 inhibitors or GLP-1 analogues compared mainly with placebo substantially influence the risk of T2DM and especially its associated complications in people at increased risk for the development of T2DM. Most trials did not investigate patient-important outcomes. PMID: 28489279 [PubMed - as supplied by publisher]
Source: Cochrane Database of Systematic Reviews - May 10, 2017 Category: General Medicine Authors: Hemmingsen B, Sonne DP, Metzendorf MI, Richter B Tags: Cochrane Database Syst Rev Source Type: research

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