scholarly journals GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review

2020 ◽  
Vol 21 (4) ◽  
pp. 1509 ◽  
Author(s):  
Yusaku Mori ◽  
Takanori Matsui ◽  
Tsutomu Hirano ◽  
Sho-ichi Yamagishi
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Animal Models ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Atherosclerotic Cardiovascular Disease ◽  
Dependent Manner ◽  
Receptor Agonists

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that are secreted from enteroendocrine L cells and K cells in response to digested nutrients, respectively. They are also referred to incretin for their ability to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner. Furthermore, GLP-1 exerts anorexic effects via its actions in the central nervous system. Since native incretin is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), DPP-resistant GLP-1 receptor agonists (GLP-1RAs), and DPP-4 inhibitors are currently used for the treatment of type 2 diabetes as incretin-based therapy. These new-class agents have superiority to classical oral hypoglycemic agents such as sulfonylureas because of their low risks for hypoglycemia and body weight gain. In addition, a number of preclinical studies have shown the cardioprotective properties of incretin-based therapy, whose findings are further supported by several randomized clinical trials. Indeed, GLP-1RA has been significantly shown to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes. However, the role of GIP in cardiovascular disease remains to be elucidated. Recently, pharmacological doses of GIP receptor agonists (GIPRAs) have been found to exert anti-obesity effects in animal models. These observations suggest that combination therapy of GLP-1R and GIPR may induce superior metabolic and anti-diabetic effects compared with each agonist individually. Clinical trials with GLP-1R/GIPR dual agonists are ongoing in diabetic patients. Therefore, in this review, we summarize the cardiovascular effects of GIP and GIPRAs in cell culture systems, animal models, and humans.

scholarly journals Utilization Rates of SGLT2 Inhibitors and GLP-1 Receptor Agonists and Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease and Type 2 Diabetes: Insights From the Department of Veterans Affairs

2022 ◽  
Author(s):  
Dhruv Mahtta ◽  
David J. Ramsey ◽  
Michelle T. Lee ◽  
Liang Chen ◽  
Mahmoud Al Rifai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Veterans Affairs ◽  
Atherosclerotic Cardiovascular Disease ◽  
Level Variation ◽  
Receptor Agonists ◽  
Drug Classes ◽  
Facility Level ◽  
Rate Ratios

<i>Objective:</i> There is mounting evidence regarding the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) and glucagon like peptide-1 receptor agonists (GLP-1RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their utilization. <p> </p> <p><i>Research Design and Methods:</i> We used the nationwide Veterans Affairs (VA) healthcare system dataset from January 1, 2020 to December 31, 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2i and GLP-1RA and the facility-level variation in their utilization. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1RA in patients with ASCVD and T2DM. </p> <p> </p> <p><i>Results:</i> Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received SGLT2i while 8.0% of patients received GLP-1RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10<sup>th</sup>-90<sup>th</sup> percentile) facility-level rates were 14.92% (9.31%-22.50%) for SGLT2i and 10.88% (4.44%-17.07%) for GLP-1RA. There was significant facility level variation among SGLT2-Is utilization - MRR<sub>unadjusted</sub> (95% CI):1.41 (1.35-1.47) and MRR<sub>adjusted</sub> (95% CI): 1.55 (1.46 – 1.63). Similar facility level variation was observed for utilization of GLP-1 RA – MRR<sub>unadjusted</sub> (95% CI):1.34 (1.29-1.38) and MRR<sub>adjusted </sub>(95% CI): 1.78 (1.65 – 1.90).</p> <p> </p> <p><i>Conclusions:</i> Overall utilization rates of SGLT2i and GLP-1RA among eligible patients are low with significantly higher residual facility-level variation in utilization of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients. </p>

scholarly journals Utilization Rates of SGLT2 Inhibitors and GLP-1 Receptor Agonists and Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease and Type 2 Diabetes: Insights From the Department of Veterans Affairs

Diabetes Care ◽  
2022 ◽  
Author(s):  
Dhruv Mahtta ◽  
David J. Ramsey ◽  
Michelle T. Lee ◽  
Liang Chen ◽  
Mahmoud Al Rifai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Veterans Affairs ◽  
Atherosclerotic Cardiovascular Disease ◽  
Level Variation ◽  
Data Set ◽  
Receptor Agonists ◽  
Drug Classes ◽  
Facility Level

OBJECTIVE There is mounting evidence regarding the cardiovascular benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their use. RESEARCH DESIGN AND METHODS We used the nationwide Veterans Affairs (VA) health care system data set from 1 January 2020 to 31 December 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2-I and GLP-1 RA and the facility-level variation in their use. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1 RA in patients with ASCVD and T2DM. RESULTS Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received an SGLT2i while 8.0% of patients received a GLP-1 RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10th–90th percentile) facility-level rates were 14.92% (9.31–22.50) for SGLT2i and 10.88% (4.44–17.07) for GLP-1 RA. There was significant facility-level variation among SGLT2-Is use—MRRunadjusted: 1.41 (95% CI 1.35–1.47) and MRRadjusted: 1.55 (95% CI 1.46 –1.63). Similar facility-level variation was observed for use of GLP-1 RA—MRRunadjusted: 1.34 (95% CI 1.29–1.38) and MRRadjusted: 1.78 (95% CI1.65–1.90). CONCLUSIONS Overall utilization rates of SGLT2i and GLP-1 RA among eligible patients are low, with significantly higher residual facility-level variation in the use of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients.

scholarly journals Utilization Rates of SGLT2 Inhibitors and GLP-1 Receptor Agonists and Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease and Type 2 Diabetes: Insights From the Department of Veterans Affairs

2022 ◽  
Author(s):  
Dhruv Mahtta ◽  
David J. Ramsey ◽  
Michelle T. Lee ◽  
Liang Chen ◽  
Mahmoud Al Rifai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Veterans Affairs ◽  
Atherosclerotic Cardiovascular Disease ◽  
Level Variation ◽  
Receptor Agonists ◽  
Drug Classes ◽  
Facility Level ◽  
Rate Ratios

<i>Objective:</i> There is mounting evidence regarding the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) and glucagon like peptide-1 receptor agonists (GLP-1RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their utilization. <p> </p> <p><i>Research Design and Methods:</i> We used the nationwide Veterans Affairs (VA) healthcare system dataset from January 1, 2020 to December 31, 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2i and GLP-1RA and the facility-level variation in their utilization. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1RA in patients with ASCVD and T2DM. </p> <p> </p> <p><i>Results:</i> Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received SGLT2i while 8.0% of patients received GLP-1RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10<sup>th</sup>-90<sup>th</sup> percentile) facility-level rates were 14.92% (9.31%-22.50%) for SGLT2i and 10.88% (4.44%-17.07%) for GLP-1RA. There was significant facility level variation among SGLT2-Is utilization - MRR<sub>unadjusted</sub> (95% CI):1.41 (1.35-1.47) and MRR<sub>adjusted</sub> (95% CI): 1.55 (1.46 – 1.63). Similar facility level variation was observed for utilization of GLP-1 RA – MRR<sub>unadjusted</sub> (95% CI):1.34 (1.29-1.38) and MRR<sub>adjusted </sub>(95% CI): 1.78 (1.65 – 1.90).</p> <p> </p> <p><i>Conclusions:</i> Overall utilization rates of SGLT2i and GLP-1RA among eligible patients are low with significantly higher residual facility-level variation in utilization of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients. </p>

Abstract P162: Comparison Of The Clinical Effect Of Empagliflozin On Glycemic And Non-glycemic Parameters In Japanese Patients With Type 2 Diabetes And Cardiovascular Disease Treated With Or Without Baseline Metformin

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Koichi Node
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Troponin I ◽  
Treatment Guidelines ◽  
Geometric Mean ◽  
Sglt2 Inhibitors ◽  
Hypoglycemic Agents ◽  
Clinical Parameters ◽  
Diabetes Status

Introduction: Recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors to be considered preferentially in patients with T2D at high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of metformin. Hypothesis: We assessed the hypothesis that the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin. Methods: This was a post hoc analysis of the Effect of Empagliflozin on Endothelial Function in Cardiovascular High Risk Diabetes Mellitus: Multi-Center Placebo-Controlled Double-Blind Randomized (EMBLEM) trial. All participants (n=105; women 31.4%; mean age 64.8 years) had both T2D and DVD and were randomized to either 24 weeks of empagliflozin 10mg daily or placebo. We assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin. Results: Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the change from baseline systolic blood pressure was greater in patients receiving metformin, compared to metformin-naïve patients (group difference -8.5 [95%CI -17.7 to 0.6 mmHg], p=0.066). Reduction in body mass index was significantly greater in patients receiving baseline metformin, relative to nonusers (-0.54 [95%CI -1.07 to -0.01] kg/m 2 , p=0.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I was 0.74 (95%CI 0.59 to 0.92, p=0.009). No obvious difference was observed in glycemic parameters, such as fasting plasma glucose and HbA1c, between the baseline metformin users and nonusers. Conclusions: Our findings suggest empagliflozin has a partially different impact on clinical parameters according to whether or not metformin has been used at baseline. As clinical opportunities for prescribing SGLT2 inhibitors are likely to increase, further research is needed to investigate the effect of SGLT2 inhibitors on clinical parameters taking into account the background situation of hypoglycemic agents, such as metformin.

scholarly journals Study on the prevalence of dyslipidemia in type 2 diabetes mellitus

2019 ◽  
Vol 6 (3) ◽  
pp. 786
Author(s):  
Eda Dayakar ◽  
C. Sathya Sree ◽  
E. Sanjay
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Type 2 Diabetic

Background: Diabetes mellitus is a common health problem globally. Dyslipidaemia is a major risk factor to develop cardiovascular disease in diabetics. They present study was undertaken to find out the prevalence of dyslipidaemia in type 2 diabetic patients.Methods: The present study was a cross sectional study consisting of 46 (23 male and 23 female) known type 2 diabetes mellitus patients. Age, gender, duration of diabetes, body mass index (BMI) was recorder in all the diabetic patients.  Fasting blood glucose levels, total cholesterol, triglycerides, HDL, LDL, VLDL levels were measured using standard methods and recorded.Results: The average total cholesterol, triglycerides, LDL, HDL and VLDL were 200±42mg/dl, 169.62±89.79mg/dl, 132.45±36.38mg/dl,39.1±16.6mg/dl and 35.85±17.09mg/dl respectively. The incidence of occurrence of hypercholesterolemia was 58.6% and hypertriglyceridemia 36.9%. Increased levels of LDL were observed in 30 (65.2%) patients and reduced HDL was observed in 43 (93.4%) patients. The incidence rate of dyslipidaemia was higher in female diabetic patients when compared to male diabetic patients.Conclusions: Awareness on the dyslipidaemia and its risk factors should be provided to the type 2 diabetic patients as they are more prone to get cardiovascular disease and lipid profile also should be monitored regularly along with blood glucose levels.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?

2021 ◽  
Vol 8 ◽  
Author(s):  
Dan Xu ◽  
Owain Chandler ◽  
Cleo Wee ◽  
Chau Ho ◽  
Jacquita S. Affandi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Diabetic Patients ◽  
Atherosclerotic Cardiovascular Disease ◽  
Healthy Individuals ◽  
Type 2 Diabetic Patients ◽  
Sodium Glucose Cotransporter ◽  
Type 2 Diabetic

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively novel class of drug for treating type 2 diabetes mellitus (T2DM) that inhibits glucose reabsorption in the renal proximal tubule to promote glycosuria and reduce blood glucose levels. SGLT2i has been clinically indicated for treating T2DM, with numerous recent publications focussing on both primary and secondary prevention of cardiovascular and renal events in Type 2 diabetic patients. The most recent clinical trials showed that SGLT2i have moderately significant beneficial effects on atherosclerotic major adverse cardiovascular events (MACE) in patients with histories of atherosclerotic cardiovascular disease. In this review and analysis, SGLT2i have however demonstrated clinically significant benefits in reducing hospitalisation for heart failure and worsening of chronic kidney disease (CKD) irrespective of pre-existing atherosclerotic cardiovascular disease or previous heart failure history. A meta-analysis suggests that all SGLT2 inhibitors demonstrated the therapeutic benefit on all-cause and cardiovascular mortality, as shown in EMPAREG OUTCOME study with a significant decrease in myocardial infarction, without increased stroke risk. All the above clinical trial recruited type 2 diabetic patients. This article aims to postulate and review the possible primary prevention role of SGLT2i in healthy individuals by reviewing the current literature and provide a prospective overview. The emphasis will include primary prevention of Type 2 Diabetes, Heart Failure, CKD, Hypertension, Obesity and Dyslipidaemia in healthy individuals, whom are defined as healthy, low or intermediate risks patients.

Sign in / Sign up

Export Citation Format

Share Document