scholarly journals Effects of a 12-Month Treatment with Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Oxidant and Antioxidant Biomarkers in Patients with Type 2 Diabetes

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1379
Author(s):  
Vaia Lambadiari ◽  
John Thymis ◽  
Dimitris Kouretas ◽  
Zoi Skaperda ◽  
Fotios Tekos ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Combined Treatment ◽  
Reducing Power ◽  
The Other ◽  
Diabetic Patients ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Imbalance between oxidative stress burden and antioxidant capacity is implicated in the course of atherosclerosis among type 2 diabetic patients. We addressed the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP1-RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on levels of oxidant and antioxidant biomarkers. We recruited a total of 160 type 2 diabetics, who received insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40), or their combination (GLP-1RA+SGLT-2i) (n = 40). We measured at baseline, at 4 and at 12 months of treatment: (a) Thiobarbituric Acid Reactive Substances(TBARS), (b) Malondialdehyde (MDA), (c) Reducing Power (RP), (d) 2,2¢-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS) and (e) Total Antioxidant Capacity TAC). Dual treatment resulted in significant improvement of TBARS, MDA, and ABTS at four months compared with the other groups (p < 0.05 for all comparisons). At twelve months, all participants improved TBARS, MDA, and ABTS (p < 0.05). At 12 months, GLP1-RA and GLP-1RA+SGLT2-i provided a greater reduction of TBARS (−8.76% and −9.83%) compared with insulin or SGLT2i (−0.5% and 3.22%), (p < 0.05). GLP1-RA and GLP-1RA+SGLT-2i showed a greater reduction of MDA (−30.15% and −31.44%) compared with insulin or SGLT2i (4.72% and −3.74%), (p < 0.05). SGLT2i and GLP-1RA+SGLT2-i showed increase of ABTS (12.87% and 14.13%) compared with insulin or GLP1-RA (2.44% and −3.44%), (p < 0.05). Only combined treatment resulted in increase of TAC compared with the other groups after 12 months of treatment (p < 0.05).12-month treatment with GLP1-RA and SGLT2i resulted in reduction of biomarkers responsible for oxidative modifications and increase of antioxidant biomarker, respectively. The combination treatment was superior and additive to each separate agent and also the beneficial effects appeared earlier.

scholarly journals Effects of glucagon like peptide-1 receptor agonists and their combination with sodium-glucose cotransporter-2 inhibitors on myocardial deformation and work index in type 2 diabetes: 1 year follow up

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
I Ikonomidis ◽  
G Pavlidis ◽  
J Thymis ◽  
D Birba ◽  
A Kalogeris ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combined Treatment ◽  
Myocardial Strain ◽  
Myocardial Deformation ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Work Index ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction: Type-2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure. Purpose We investigated the effect of novel antidiabetic drugs, glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on myocardial function. Methods A hundred-sixty T2DM patients (age: 58 ± 10years) were randomized to insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40) or their combination (GLP-1RA + SGLT-2i) (n = 40) as add-on to metformin. We measured at baseline and 1 year post-treatment: a) global LV longitudinal strain (GLS), systolic (GLSR) and diastolic (GLSR E) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial work index (GWI), global constructive (GCW) and global wasted work (GWW) derived by pressure-myocardial strain loops using speckle tracking imaging. Results After 1 year of treatment, all patients improved GLS, GCS, GRS and pUtwVel (p &lt; 0.05). GLP-1RA or GLP-1RA + SGLT-2i provided a greater increase of GLS (11.5% and 13% vs. 6.8% and 2.3%), GWI (12.7% and 17.4% vs. 3.1% and 2%), GCW (12.3% and 15% vs. 2.2% and 7.8%) and a greater reduction of GWW (38.7% and 41.6% vs. 13.5% and 4.9%) compared with insulin or SGLT-2i, despite a similar HbA1c reduction (p &lt; 0.05 for all comparisons) (Table). Patients under combined treatment with GLP-1RA + SGLT-2i achieved a 2-fold reduction of pTw and a 2-fold increase of pUtwVel than those under each one regimen or insulin (p &lt; 0.05). The dual therapy showed the greatest effect on measured myocardial markers in LVEF &lt; 55% (p &lt; 0.05). Conclusions One year treatment with GLP-1RA or combination of GLP-1RA and SGLT-2i resulted in a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT-2i treatment, independently of glycemic control in T2DM. All patients (n = 160) Insulin (n = 40) GLP-1RA (n = 40) SGLT-2i (n = 40) GLP-1RA + SGLT-2i (n = 40) p-value GLS, % Baseline -16.4 ± 3.7 -16.4 ± 3.5 -16.2 ± 3.5 -17 ± 4 -16 ± 4 0.139 1 year -17.9 ± 3.9 -17.6 ± 4.2 -18.3 ± 3.5 -17.4 ± 3.4 -18.4 ± 4.7 0.003 GWI, mmHg% Baseline 1538 ± 430 1644 ± 416 1510 ± 403 1536 ± 535 1463 ± 362 0.116 1 year 1692 ± 412 1696 ± 377 1730 ± 318 1568 ± 456 1772 ± 499 0.006 pTw, deg Baseline 15.7 ± 6 16 ± 5.1 15.6 ± 5 15.2 ± 6 16.1 ± 8 0.910 1 year 14.6 ± 5.1 15.4 ± 5.4 14.4 ± 5.4 14.7 ± 4.6 14 ± 5 0.034 pUtwVel, deg/s Baseline -104 ± 42 -100 ± 44 -107 ± 41 -101 ± 28 -111 ± 54 0.550 1 year -116 ± 49 -107 ± 55 -114 ± 45 -108 ± 38 -134 ± 61 0.017 Table

scholarly journals Glucagon like peptide-1 receptor agonists and their combination with sodium-glucose cotransporter-2 inhibitors improve myocardial deformation and work index in type-2 diabetes after 12-month treatment

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Ikonomidis ◽  
G Pavlidis ◽  
J Thymis ◽  
D Birba ◽  
A Kalogeris ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combined Treatment ◽  
Post Treatment ◽  
Myocardial Deformation ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Work Index ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background/Introduction Type-2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on LV myocardial function of T2DM patients. Methods A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40) as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) global LV longitudinal strain (GLS), systolic (LongSr) and diastolic (LongSrE) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial global work index (GWI), global constructive (GCW) and global wasted myocardial work (GWW) derived by pressure-myocardial strain loops using speckle tracking imaging. Results At 4 and 12 months post-treatment, all patients improved GLS, GCS, GRS and pUtwVel (p&lt;0.05). At 12 months, GLP-1RA or GLP-1RA+SGLT-2i provided a greater increase of GLS (11.5% and 13% vs. 6.8% and 2.3%), GCS (11.9% and 14.6% vs. 7.3% and 3.4%), GRS (3.8% and 4.3% vs. 2.2% and 1.6%), GWI (12.7% and 17.4% vs. 3.1% and 2%), GCW (12.3% and 15% vs. 2.2% and 7.8%) and a greater reduction of GWW (38.7% and 41.6% vs. 13.5% and 4.9%) compared with insulin or SGLT-2i, despite a similar HbA1c reduction (p&lt;0.05 for all comparisons) (Table). Patients under combined treatment with GLP-1RA+SGLT-2i achieved a 2-fold reduction of pTw and a 2-fold increase of pUtwVel than those under each one regimen or insulin (p&lt;0.05). The dual therapy showed the greatest effect on measured myocardial markers in patients with LVEF &lt;55% (p&lt;0.05). Conclusions Twelve-month treatment with GLP-1RA or combination of GLP-1RA and SGLT-2i showed a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT-2i treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

scholarly journals Glucagon-Like Peptide 1 Receptor Agonists and Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (12) ◽  
pp. 1205-1218 ◽  
Author(s):  
Muhammad Shahzeb Khan ◽  
Gregg C. Fonarow ◽  
Darren K. McGuire ◽  
Adrian F. Hernandez ◽  
Muthiah Vaduganathan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Ejection Fraction ◽  
Atherosclerotic Cardiovascular Disease ◽  
Reduced Ejection Fraction ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease– and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.

scholarly journals Glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized clinical trials

2009 ◽  
Vol 160 (6) ◽  
pp. 909-917 ◽  
Author(s):  
Matteo Monami ◽  
Niccolò Marchionni ◽  
Edoardo Mannucci
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Relevant Information ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

ObjectiveThe role of glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes is debated; many recent trials, which were not included in previous meta-analyses, could add relevant information.Design and methodsAll available randomized controlled trials (RCTs), either published or unpublished, performed in type 2 diabetic patients with GLP-1 receptor agonists (exenatide and liraglutide), with a duration>12 weeks were meta-analysed for HbA1c, body mass index, hypoglycaemia and other adverse events.Results and conclusionsA total of 21 RCTs (six of which unpublished), enrolling 5429 and 3053 patients (with GLP-1 receptor agonists and active comparator or placebo respectively), was retrieved and included in the analysis. GLP-1 receptor agonists determine a significant improvement of HbA1c in comparison with placebo (−1.0 (−1.1, −0.8),P<0.001), with a low risk of hypoglycaemia. There is no evidence of increased cardiovascular risk with the use of GLP-1 receptor agonists. GLP-1 receptor agonists, which induce weight loss, are associated with gastrointestinal side effects. GLP-1 receptor agonists are effective in reducing HbA1c and postprandial glucose. In patients failing to sulphonylureas and/or metformin, GLP-1 receptor agonists are similarly effective as insulin. Available data suggest that the efficacy and tolerability of the novel agent, liraglutide, which is adequate for once-a-day administration, are comparable with those of exenatide bis in die.

Fighting Type-2 Diabetes: Present and Future Perspectives

2019 ◽  
Vol 26 (10) ◽  
pp. 1891-1907 ◽  
Author(s):  
Cai-Guo Yu ◽  
Ying Fu ◽  
Yuan Fang ◽  
Ning Zhang ◽  
Rong-Xin Sun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glycemic Control ◽  
Clinical Results ◽  
Diabetic Patients ◽  
Β Cells ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: Type-2 diabetes mellitus accounts for 80-90% of diabetic patients. So far, the treatment of diabetes mainly aims at elevating insulin level and lowering glucose level in the peripheral blood and mitigating insulin resistance. Physiologically, insulin secretion from pancreatic β cells is delicately regulated. Thus, how insulin-related therapies could titrate blood glucose appropriately and avoid the occurrence of hypoglycemia remains an important issue for decades. Similar question is addressed on how to attenuate vascular complication in diabetic subjects. Methods: We overviewed the evolution of each class of anti-diabetic drugs that have been used in clinical practice, focusing on their mechanisms, clinical results and cautions. Results: Glucagon-like peptide-1 receptor agonists stimulate β cells for insulin secretion in response to diet but not in fasting stage, which make them superior than conventional insulinsecretion stimulators. DPP-4 inhibitors suppress glucagon-like peptide-1 degradation. Sodium/ glucose co-transporter 2 inhibitors enhance glucose clearance through urine excretion. The appearance of these new drugs provides new information about glycemic control. We update the clinical findings of Glucagon-like peptide-1 receptor agonists, DPP-4 inhibitors and Sodium/glucose cotransporter 2 inhibitors in glycemic control and the risk or progression of cardiovascular disease in diabetic patients. Stem cell therapy might be an alternative tool for diabetic patients to improve β cell regeneration and peripheral ischemia. We summarize the clinical results of mesenchymal stem cells transplanted into patients with diabetic limb and foot. Conclusion: A stepwise intensification of dual and triple therapy for individual diabetic patient is required to achieve therapeutic target.

scholarly journals Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

BMJ ◽  
2021 ◽  
pp. m4573 ◽  
Author(s):  
Suetonia C Palmer ◽  
Britta Tendal ◽  
Reem A Mustafa ◽  
Per Olav Vandvik ◽  
Sheyu Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
High Risk ◽  
Meta Analysis ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Randomised Controlled

Abstract Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool ( https://magicevidence.org/match-it/200820dist/#!/ ) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180.

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