Prescribing paradigm shift? Applying the 2019 European Society of Cardiology-led guidelines on ‘diabetes, pre-diabetes, and cardiovascular disease’ to assess eligibility for sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists as first-line monotherapy (or add-on to metformin monotherapy) in type 2 diabetes in Scotland

Objective: In 2019, the European Society of Cardiology led and released new guidelines for diabetes’ cardiovascular risk management, reflecting recent evidence of cardiovascular disease (CVD) reduction with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and some glucagon-like peptide-1 receptor agonists (GLP1RA) in type 2 diabetes (T2D). A key recommendation is that all those with T2D who are (anti-hyperglycaemic) drug-naïve or on metformin monotherapy should be CVD-risk-stratified and an SGLT-2i or GLP1RA initiated in all those at high or very high risk, irrespective of glycated haemoglobin. We assessed the impact of these guidelines in Scotland were they introduced as is. Research Design and Methods: Using a nationwide diabetes register in Scotland, we did a cross-sectional analysis, employing variables in our register for risk stratification at 1 January 2019. We were conservative in our definitions, assuming the absence of a risk factor where data were not available. The risk classifications were applied to those drug-naïve or metformin monotherapy people and the anticipated prescribing change calculated. Results: Of the 265,774 people with T2D in Scotland, 53,194 (20.0% of T2D) were drug-naïve and 56,906 (21.4%) were on metformin monotherapy. Of these, 74.5% and 72.4% respectively were estimated as at least high risk given the guideline risk definitions. Conclusion: Thus, 80,830 (30.4%) of all those with T2D (n=265,774) would start one of these drug classes according to table 7 and figure 3 of the guideline. The sizeable impact on drug budgets, enhanced clinical monitoring and the trade-off with reduced CVD-related healthcare costs will need careful consideration.

Download Full-text

Prescribing paradigm shift? Applying the 2019 European Society of Cardiology-led guidelines on ‘diabetes, pre-diabetes, and cardiovascular disease’ to assess eligibility for sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists as first-line monotherapy (or add-on to metformin monotherapy) in type 2 diabetes in Scotland

10.2337/figshare.12167802 ◽

2020 ◽

Author(s):

Caparrotta Thomas M ◽

Blackbourn Luke AK ◽

McGurnaghan Stuart J ◽

Chalmers John ◽

Lindsay Robert ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

High Risk ◽

European Society ◽

Metformin Monotherapy ◽

Drug Naïve ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

European Society Of Cardiology

Download Full-text

Prescribing Paradigm Shift? Applying the 2019 European Society of Cardiology–Led Guidelines on Diabetes, Prediabetes, and Cardiovascular Disease to Assess Eligibility for Sodium–Glucose Cotransporter 2 Inhibitors or Glucagon-Like Peptide 1 Receptor Agonists as First-Line Monotherapy (or Add-on to Metformin Monotherapy) in Type 2 Diabetes in Scotland

Diabetes Care ◽

10.2337/dc20-0120 ◽

2020 ◽

Vol 43 (9) ◽

pp. 2034-2041 ◽

Cited By ~ 5

Author(s):

Thomas M. Caparrotta ◽

Luke A.K. Blackbourn ◽

Stuart J. McGurnaghan ◽

John Chalmers ◽

Robert Lindsay ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Paradigm Shift ◽

First Line ◽

Sodium Glucose Cotransporter ◽

Metformin Monotherapy ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

European Society Of Cardiology

Download Full-text

Abstract 15526: Glucagon-like Peptide-1 Receptor Agonists Reduce Adverse Cardiovascular Disease (CVD) Events in Patients With Type 2 Diabetes: An Assessment of Heterogeneity Among CVD Outcomes and a Meta-regression Analysis

Circulation ◽

10.1161/circ.142.suppl_3.15526 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Simran Grewal ◽

Ninad Zaman ◽

Louis Borgatta ◽

Matthew Nudy ◽

Brandon Peterson

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cardiovascular Death ◽

Nonfatal Stroke ◽

Significant Heterogeneity ◽

Receptor Agonists ◽

Meta Regression ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Introduction: Recent evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce adverse cardiovascular disease (CVD) events. The objective of this study is to analyze randomized controlled trials (RCTs) testing GLP-1 RA’s effects on CVD among participants with type 2 diabetes (T2DM). Methods: RCTs comparing GLP-1 RA versus placebo among participants with T2DM were identified using PubMed and Cochrane databases. The endpoints of this analysis included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi 2 and I 2 tests. For any endpoint with significant heterogeneity, a meta-regression was performed using baseline hemoglobin A1C (A1C) in each RCT as the moderator and a R 2 value was calculated. Results: 7 RCTs (N = 56,004) were identified with 174,163 patient years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83-0.95], cardiovascular death [RR 0.88, 95% CI 0.81-0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77-0.94]. There was no significant heterogeneity among these RCTs (Figure 1). GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.82-1.02]. However, there was significant heterogeneity among these RCTS (Chi 2 =12.94, p=0.04, I 2 =54%). When accounting for A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p=0.23, I 2 =27%). A relationship between A1C and GLP-1 RA’s effect on nonfatal MI (R 2 =0.64, Figure 1) was observed when performing the meta-regression. Conclusion: GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke in patients with T2DM with minimal heterogeneity among RCTs. GLP-1 RA did not reduce nonfatal MI, however there may be an association between A1C and GLP-1 RA’s effect on nonfatal MI.

Download Full-text

Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-001020 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001020 ◽

Cited By ~ 1

Author(s):

Bhavani Shankara Bagepally ◽

Usa Chaikledkaew ◽

Yogesh Krishnarao Gurav ◽

Thunyarat Anothaisintawee ◽

Sitaporn Youngkong ◽

...

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Fixed Effects ◽

Evaluation Studies ◽

Meta Analysis ◽

Cost Effective ◽

Metformin Monotherapy ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

ObjectivesTo conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM) after metformin monotherapy failure.Research design and methodsThe study design is a systematic review and meta-analysis. We searched MEDLINE (via PubMed), Scopus and Tufts Registry for eligible cost–utility studies up to June 2018, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We conducted a systematic review and pooled the INBs of GLP1s compared with other therapies in T2DM after metformin monotherapy failure. Various monetary units were converted to purchasing power parity, adjusted to 2017 US$. The INBs were calculated and then pooled across studies, stratified by level of country income; a random-effects model was used if heterogeneity was present, and a fixed-effects model if it was absent. Heterogeneity was assessed using Q test and I2 statistic.ResultsA total of 56 studies were eligible, mainly from high-income countries (HICs). The pooled INBs of GLP1s compared with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=10), sulfonylureas (n=6), thiazolidinedione (TZD) (n=3), and insulin (n=23) from HICs were US$4012.21 (95% CI US$−571.43 to US$8595.84, I2=0%), US$3857.34 (95% CI US$−7293.93 to US$15 008.61, I2=45.9%), US$37 577.74 (95% CI US$−649.02 to US$75 804.50, I2=92.4%) and US$14 062.42 (95% CI US$8168.69 to US$19 956.15, I2=86.4%), respectively. GLP1s were statistically significantly cost-effective compared with insulins, but not compared with DPP4i, sulfonylureas, and TZDs. Among GLP1s, liraglutide was more cost-effective compared with lixisenatide, but not compared with exenatide, with corresponding pooled INBs of US$4555.09 (95% CI US$3992.60 to US$5117.59, I2=0) and US$728.46 (95% CI US$−1436.14 to US$2893.07, I2=0), respectively.ConclusionGLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs.PROSPERO registration numberCRD42018105193.

Download Full-text

Usefulness of Glucagon-Like Peptide-1 Receptor Agonists to Reduce Adverse Cardiovascular Disease Events in Patients with Type 2 Diabetes Mellitus

The American Journal of Cardiology ◽

10.1016/j.amjcard.2021.05.043 ◽

2021 ◽

Author(s):

Simran Grewal ◽

Ninad Zaman ◽

Louis Borgatta ◽

Matthew Nudy ◽

Andrew J. Foy ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type 2 Diabetes Mellitus ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Download Full-text

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 ◽

10.1136/bmj.m4573 ◽

2021 ◽

pp. m4573 ◽

Cited By ~ 1

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.

Download Full-text

Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases

European Journal of Preventive Cardiology ◽

10.1177/2047487319880040 ◽

2019 ◽

Vol 26 (2_suppl) ◽

pp. 73-80 ◽

Cited By ~ 18

Author(s):

Francesco Prattichizzo ◽

Lucia La Sala ◽

Lars Rydén ◽

Nikolaus Marx ◽

Marc Ferrini ◽

...

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Receptor Agonist ◽

Glucose Lowering ◽

Patients With Diabetes ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Type 2 diabetes mellitus is a major risk factor for developing cardiovascular disease, and many patients with diabetes have prevalent cardiovascular complications. Recent cardiovascular outcome clinical trials suggest that certain new glucose-lowering drugs are accompanied by additional cardioprotective properties. Indeed, selected glucagon-like peptide-1 receptor agonists have a proved cardiovascular benefit in terms of a reduced incidence of ischaemic events, while sodium/glucose co-transporter-2 inhibitors have also shown significant protection, with a striking effect on heart failure and renal endpoints. These findings have been integrated in recent guidelines which now recommend prescribing (when initial metformin monotherapy fails) a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor with clinical trial-confirmed benefit in patients with diabetes and atherosclerotic cardiovascular disease, and a sodium/glucose co-transporter-2 inhibitor in such patients with heart failure or chronic kidney disease at initial stages. Furthermore, the new 2019 European Society of Cardiology guidelines in collaboration with the European Association for the Study of Diabetes recommend a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor in treatment-naive patients with type 2 diabetes mellitus with pre-existing cardiovascular disease or at high cardiovascular risk. Future research will disentangle the mechanisms underpinning these beneficial effects and will also establish to what extent these results are generalisable to the whole diabetes population. In the meantime, available evidence should prompt a wide diffusion of these two classes of drugs among patients with diabetes and cardiovascular disease. Here, we briefly summarise recent findings emerging from cardiovascular outcome clinical trials, discuss their impact on treatment algorithms and propose new possible approaches to improve our knowledge further regarding the cardiovascular effect of glucose-lowering medications.

Download Full-text