Key takeaways:
- GLP-1 advantages persist no matter background SGLT2 inhibitor use.
- Optimum technique for coronary heart failure screening is debated.
- New insights into the mechanistic results of mineralocorticoid receptor antagonists.
PHILADELPHIA — Throughout a session on the Coronary heart in Diabetes CME Convention, audio system highlighted 4 papers not too long ago revealed in Circulation that advance the sector of cardiometabolic analysis.
Darren Ok. McGuire
“Annually [for Heart in Diabetes], I’ve gleaned the journal to select 4 or 5 of the very best papers we’ve revealed associated to diabetes,” Darren Ok. McGuire, MD, MHSc, deputy editor of Circulation and professor of medication, the Dallas Coronary heart Ball Chair for Analysis on Coronary heart Illness in Girls and Distinguished Instructing Professor at College of Texas Southwestern Medical Middle, stated right here.
Learn on for this yr’s highlights, in no explicit order.
GLP-1 advantages constant no matter SGLT2 inhibitor use
Remedy with a GLP-1 receptor agonist yielded cardiovascular and kidney advantages for adults with kind 2 diabetes, no matter whether or not they have been utilizing an SGLT2 inhibitor, in response to a scientific evaluate and meta-analysis.
Richard E. Pratley
“In scientific apply, we’re utilizing these drugs collectively on a regular basis. We achieve this as a result of we expect they’ve complementary mechanisms of motion. However what’s actually the proof that they work effectively together with one another?” Richard E. Pratley, MD, the Samuel E. Crockett Chair in Diabetes Analysis, medical director of AdventHealth Diabetes Institute and a Healio | Endocrine At the moment Co-editor, stated right here.
The systematic evaluate and meta-analysis targeted on three randomized, double-blind, placebo-controlled trials in kind 2 diabetes with a GLP-1 because the research therapy in contrast with placebo: Concord Outcomes (albiglutide, GSK), AMPLITUDE-O (efpeglenatide, Sanofi) and FLOW (semaglutide, Novo Nordisk). Every trial had subgroup knowledge based mostly on background SGLT2 inhibitor use.
Amongst 17,000 members, 10.2% have been on an SGLT2 inhibitor at baseline.
“The consequences on cardiovascular and kidney outcomes and mortality have been constant no matter SGLT2 inhibitor use at baseline, which means that GLP-1 and SGLT2 inhibitors have been prone to have unbiased and additive results on scientific outcomes in sufferers with kind 2 diabetes,” Pratley stated.
Screening for coronary heart failure
The optimum method to determine sufferers with diabetes and with out atherosclerotic CVD who’re at excessive danger for growing coronary heart failure is debated.
Shahzeb Khan, MD, MSc, a heart specialist on the Baylor Scott and White Analysis Institute, Baylor Scott and White Cardiac Imaging Core Lab, The Coronary heart Hospital Plano, mentioned outcomes from an evaluation of almost 6,300 sufferers in seven community-based cohorts. The researchers seemed on the affect of various HF screening methods to foretell danger: the WATCH-DM danger rating, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T and echocardiography. They additional evaluated a one-step screening technique and a two-step screening technique.
Six % of sufferers developed incident HF throughout 5 years of follow-up.
“A two-step screening technique utilizing scientific danger scores adopted by biomarker testing is perhaps probably the most optimum, efficient and cost-effective technique to display screen for sufferers with coronary heart failure and sort 2 diabetes. In case you use a one-step screening technique — for instance, utilizing biomarkers — we is perhaps lacking numerous sufferers who would possibly develop coronary heart failure as a result of there’s numerous residual danger,” Khan stated through the presentation.
Mineralocorticoid receptor antagonists in diabetes, CKD
Sanjay Rajagopalan
Sanjay Rajagopalan, MD, MBA, mentioned new insights into the mechanistic results of mineralocorticoid receptor antagonists in sufferers with kind 2 diabetes and persistent kidney illness.
There’s a lack of mechanistic investigation on the pathways by which mineralocorticoid receptor antagonism would possibly scale back CV danger in sufferers with diabetes and CKD, in response to Rajagopalan, who’s chief of the division of cardiovascular medication and chief educational and scientific officer of College Hospitals Harrington Coronary heart & Vascular Institute and Herman Ok. Hellerstein, MD, Chair in Cardiovascular Analysis at Case Western Reserve College.
The MAGMA trial included 79 sufferers with high-risk kind 2 diabetes and CKD who have been receiving maximally tolerated renin-angiotensin system blockade. Sufferers have been randomly assigned to spironolactone 25 mg or placebo and follow-up was carried out at 1 yr.
“On this small research, spironolactone 25 mg considerably decreased % wall quantity of the thoracic aortic at 12 months [and] placebo-adjusted left ventricular mass was diminished by 9 g by spironolactone,” which is bigger than that seen in SGLT2 inhibitor trials, Rajagopalan stated.
The progressive enhance in native T1 values probably reflecting fibrosis was attenuated by spironolactone therapy, he stated.
Remedy with spironolactone additionally considerably lowered 24-hour blood stress.
“The proteomic profile reveals vital downregulation of pathways concerned in irritation, cytokine activation and immunity,” Rajagopalan stated.
Implementation of guideline-directed medical remedy
The therapy panorama for kind 2 diabetes and CKD has undergone a “transformational change” over the previous 5 years, Muthiah Vaduganathan, MD, MPH, and colleagues wrote in a 2024 Circulation paper.
The main diabetes, cardiology and nephrology societies advocate 4 pillars of guideline-recommended medical remedy for kind 2 diabetes and CKD: renin-angiotensin system blockade, SGLT2 inhibitor, nonsteroidal mineralocorticoid receptor antagonist (finerenone [Kerendia, Bayer]) and GLP-1s.
“In 2025, it’s a exceptional interval for CKD as a result of simply as we’ve 4 [pillars of treatment] for coronary heart failure, so do we’ve that in CKD,” stated Vaduganathan, heart specialist and co-director of the Middle for Cardiometabolic Implementation Science at Brigham and Girls’s Hospital and on college at Harvard Medical College.
Vaduganathan mentioned a framework for 3 potential approaches to the initiation and timing of the 4 pillars of guideline-directed medical remedy:
- A conventional method includes including therapies in historic order (maximize renin-angiotensin system blockade, add SGLT2 inhibitor, reassess in 3 to six months, add nonsteroidal mineralocorticoid receptor antagonist, take into account GLP-1).
- A rapid-sequence method includes initiation of all guideline-directed medical therapies concurrently or in a speedy timeframe.
- An accelerated risk-based method includes use of a validated danger rating (for instance, KDIGO) to determine the highest-risk sufferers and prioritizes accelerated implementation of guideline-directed medical remedy.
Every method has its personal professionals and cons, Vaduganathan stated. For instance, following a standard method might take as much as 1 yr till all guideline-directed medical therapies are totally carried out. Then again, a rapid-sequence method may simplify care and will thus be adopted to a higher diploma, he stated. Nonetheless, this method raises considerations about assuming danger and value effectiveness, he stated. Following an accelerated risk-based method helps prioritize sufferers prone to acquire the best advantages, and full implementation of guideline-directed medical therapies might take 6 to 12 months — someplace in between the opposite two approaches, Vaduganathan stated.
The authors stated it’s essential to additional develop and refine these approaches to maximise the potential of mixture guideline-directed medical remedy for this inhabitants.
References:
Sources/Disclosures
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Pratley R, et al. Joint Session – Circulation. Offered at: Coronary heart in Diabetes CME Convention; June 6-8, 2025; Philadelphia.
Disclosures:
Healio couldn’t affirm related monetary disclosures for Khan on the time of publication. Pratley experiences receiving speaker charges from Abbott, Corcept, Eli Lilly and Novo Nordisk; marketing consultant charges from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Prescription drugs, Corcept, Eli Lilly, Endogenex, F. Hoffmann-La Roche, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical Co., Lexicon, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Solar Prescription drugs Industries and Verdiva Bio Dev Ltd.; analysis grants from Boehringer Ingelheim, Carmot, Dompe, Eli Lilly, Endogenex, Novo Nordisk and Sanofi; and inventory choices from Altanine. Rajagopalan experiences receiving funding from the NIH for MAGMA, serving on a scientific advisory board for Bayer and Novo Nordisk and talking for Novo Nordisk. Vaduganathan experiences receiving analysis grant assist, serving on advisory boards and/or speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Esperion, Fresenius Medical Care, Idorsia, Lexicon, Merck, Milestone Prescription drugs, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi and Tricog Well being and collaborating on scientific trial committees for research sponsored by Amgen, AstraZeneca, Boehringer Ingelheim, Galmed, Novartis, Bayer AG, Occlutech, Pharmacosmos and Impulse Dyanamics.
