Patrick Holmes @drpatrickholmes

#ADA2026 #Zenagamtide (Amycretin) Delivers in #T2D 💥 Dual GLP-1 + amylin agonist shows impressive HbA1c & weight reductions with no apparent weight-loss plateau 🧪 Phase 2b (n=226; T2D on metformin ± SGLT2i) 🩸 HbA1c:  ⤵️1.41%(10mg) − 1 .71% (40 mg) vs ⤵️0.14% (pbo) 🎯 HbA1c ≤6.5% achieved:  76% (40 mg) vs 14% (pbo) 📉 Mean weight loss at 36 wks: ⤵️12.9(10mg) − 14.6% (40 mg) vs ⤵️2.1% (pbo) 📊 CGM metrics improved across all doses 🤢 GI AEs were the most common, with rates broadly consistent with GLP-1 and amylin therapies 💡 Notably, the 20 mg group had only 8w at maintenance dose and the 40 mg group only 4w, yet weight loss curves were still trending downward at 36w 👉 One of the strongest combinations of glycaemic and weight efficacy seen to date in T2D❗️ 📌 Poster 1730-P

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This is shocking 😮. Just happened at the start of #ADA2026 Scientific Sessions.

🚨 DiRECT 5-yr data in Diabetic Medicine 👉Primary care low-energy diet: 6.1 kg weight loss, 10% T2D remission at 5 yr (46% → 36% → 10%). 💰Modelled cost dominance over usual care. Lifetime QALY +0.08, cost -£496. 10% reads as failure to some. It isn't. Obesity and T2D are chronic relapsing conditions. Remission ≠ cure. The clinical point worth flagging: 🔹 Patients pursue remission to come off meds. Fair 🔸 Remission isn't licence to drop evidence-based CV prevention 🔹 NICE increasingly puts metformin + SGLT2i as starting point for many adults with T2D 🔸 Statins still matter. CTT: ~22% major vascular event reduction per 1 mmol/L LDL fall 🔹 BP and lipid control need reassessing after remission, not assuming resolved Incretins offer larger weight loss and hard CV data in selected groups (SUSTAIN-6,SELECT, FLOW). DiRECT doesn't. It's a tool. Use it wisely. 🔗 doi.org/10.1111/dme.70…

🔍 10% Visceral Fat loss⤵️ T2D cases by 28% over 10y 5- and 10-yr follow-up of two 18-mo lifestyle RCTs. The story isn’t the weight loss. It’s what stayed lost after the weight came back: 🔹 VAT -27% at 18 mo (MRI) 🔸 5–10 yr later: weight fully regained. VAT still ~15% below baseline (~55–60% of original loss preserved) 🔹 Each 10% VAT loss = 28% lower T2D risk in follow-up (HR 0.72). Association, not proof 🔸 Liver and pancreatic fat fully regained Track waist, not just weight. 🔗 doi.org/10.1161/CIRCUL…

🚨 TRIUMPH-1: #retatrutide topline data🚨 Phase 3, n=2,339, 80 wk, obesity without diabetes (efficacy estimand): 🔹 12 mg: -28.3% body weight (-31.9 kg) 🔸 9 mg: -25.9% | 4 mg: -19.0% | Placebo: -2.2% 🔹 ≥30% weight loss: 45.3% vs 0.5% 🔸 104-wk extension (BMI ≥35, n=532), 12 mg → MTD: -30.3% Cross-trial context (obesity, no diabetes): 🔹 STEP-1 SEMA 2.4 mg, 68 wk: -14.9% 🔸 SURMOUNT-1 TZP 15 mg, 72 wk: -20.9% 🔹 TRIUMPH-1 RETA 12 mg, 80 wk: -28.3% ⚠️But: 🔸 Topline press release. No peer-reviewed publication yet 🔹 AE discontinuation at 12 mg: 11.3% vs 4.9% placebo 🔸 Dysesthesia 5.1–12.5% vs 0.9%. Efficacy ceiling keeps moving. Enthusiasm needs caution. Still unlicensed in humans outside of research❗️ 🔗 investor.lilly.com/news-releases/…

🚨NICE TA1152: #semaglutide 2.4 mg recommended as an option for ⤵️💔risk in adults with established CVD and BMI ≥27 kg/m² 🚨 🔹 Eligible: previous MI, ischaemic/haemorrhagic stroke, or symptomatic PAD, with BMI ≥27. No restriction on time since index event. T2D not excluded. 🔸 SELECT (n=17,604): First MACE: HR 0.80 (0.72-0.90) Non-fatal MI: HR 0.72 (0.61-0.85) Coronary revasc: HR 0.77 (0.68-0.87) All-cause death: HR 0.81 (0.71-0.93) Benefit appeared early, before substantial weight loss. 🔹 Preferred ICERs £6,878 to £14,594 per QALY, well below the £20,000 threshold. 🔸 What a TA means for access: statutory funding mandate. ICBs in England must make it available within 90 days when considered the right treatment (Wales: 60 days from final draft). But that doesn't mean immediate primary care prescribing. 🔗 nice.org.uk/guidance/ta1152 #PrimaryCare #Cardiology #GLP1 #NICE

Apologies if anyone got some random DM from me I was hacked!!!!

🍷 First RCT of semaglutide 2.4mg in treatment-seeking patients with alcohol use disorder + obesity n=108 26 weeks semaglutide + CBT vs placebo + CBT Primary endpoint (% heavy drinking days): 🔹 Semaglutide: -41.1pp 🔸 Placebo: -26.4pp 🔹 Difference: -13.7pp (p=0.0015) Secondary endpoints consistent: total alcohol intake, drinks per drinking day, WHO risk level, craving all favoured semaglutide. Phosphatidyl ethanol supported self-report. Safety: GI AEs higher (nausea 57% vs 7%). 4 vs 1 discontinued for AEs. No pancreatitis. Caveats: BMI ≥30 only, single centre, no post-trial follow-up. Weight loss correlated with drinking reduction (ρ=-0.40). Moves beyond hypothesis-generating. Replication needed before off-label use.

#type2diabetes #Obesity 🔬 A quintuple agonist combining GLP-1R/GIPR co-agonism with pan-PPAR agonism (α/γ/δ) in a single molecule. 🎯delivery of lanifibranor at ~6,900x lower dose than standalone. ✅Outperformed semaglutide and dual agonism in DIO 🐁. Glycaemic benefit partly weight-independent. Preclinical. But the approach is worth 👀 #GoggleDocs review 🔗 doi.org/10.1038/s41586…

"Our patients don't live in silos. It's time we stopped working in them." 📢TONIGHT 7pm. Free webinar with @drkevinfernando launching The CKM Collaborative. Cardiovascular. Kidney. Metabolic. One story. Still time to join the 100+ registered 💻 tinyurl.com/3hszjs5s

As predicted? A slow burn demise of an experiment with population health in primary care Led by grassroots Overturning Royal Colleges and national bodies Implementing @lengreview without actually implementing it Fascinating approach from @DHSCgovuk ps Change to improve safety? Is possible Needs a whole lot of determination too

@drmahendrapatel @JonnyUnderhill @DM_Zadeh @LUFC @apopey @willowhaye @cmmillar @ashleydcohen @wrexhamrob Give them a cheer for me. I wasn’t successful in the ballot so will be watching on TV. MOT 🤍💛💙🤞🏻☘️

🆕 BJGP qualitative study: why isn't CKD risk stratification happening in primary care❓ The guidelines exist. The therapies exist. So what's getting in the way? Key barriers identified: 1⃣ Time: CKD consultations are complex, competing priorities win 2⃣ Incentives: no QOF since 2014, uACR completion ~50% 3⃣ System design: results reviewed by clinicians who don't know the patient 4⃣ Communication anxiety: fear of "pathologising" patients 5⃣ Low awareness of KFRE and @goKDIGO risk grid Diagnostic criteria universally understood. Risk stratification tools? Barely on the radar. The clinicians interviewed are thoughtful and conscientious. Awareness isn't the problem. Practical barriers are. Guidelines are necessary but not sufficient. This study maps where implementation gaps actually sit. 🔗bjgp.org/content/early/…

🚨💊 ACHIEVE-4: #Orforglipron CV safety data out today🚨 👉Key findings (n=2,749, T2D + high CV risk): ✅ MACE-4 vs insulin glargine: HR 0.84 (0.59-1.20) non-inferiority met 🟠 All-cause mortality: HR 0.43 (0.25-0.75) ⚠️striking, but not multiplicity-adjusted ⤵️ HbA1c: -1.6% vs -1.0% ⤵️ Weight: -8.8% vs +1.7% Important context: 🔹This was NOT a placebo-controlled CVOT. 🔸Comparator was insulin glargine. 🔹Unlike LEADER/SUSTAIN-6/REWIND, we can't directly quantify CV benefit vs placebo. Non-inferiority to an active comparator ≠ cardioprotection. 🔸Similar challenge to SURPASS-CVOT (tirzepatide vs dulaglutide). 👉CV safety confirmed. CV benefit? Not yet proven. 👉Ongoing CVOT ACHIEVE-5 may answer this 🔗investor.lilly.com/news-releases/…

Happy to share our new publication on GLP-1, sarcopenia and frailty. Here, we conclude that weight loss itself (rather than GLP-1 signaling) needs to be carefully monitored in elderly patients to properly balance risk/benefit ratios. nature.com/articles/s4157… @NatureRevEndo

🔥My latest @Medscape Medical Mentor podcast is live! 🎯Diagnosing & managing erectile dysfunction in primary care ❤️ ED can precede a CV event by 3-5y and is associated with >1.5x ⬆️ risk for CVD On @Spotify , @ApplePodcasts & @Medscape website – link in comments 👇🏾

🩺 SGLT2i + high HbA1c = higher DKA risk? New meta-analysis (22 studies, 1.3M patients): 🔹 HbA1c ≥67 mmol/mol (8.3%): DKA risk RR 1.63 🔸 HbA1c <67 mmol/mol: No significant increase (RR 1.10) 🔹 Significant effect modification (p=0.018) Practical approach when HbA1c is very high: 🔸 Rescue therapy first (SU or insulin) to bring glucose down 🔹 Add SGLT2i for CV/renal protection once stabilised 🔸 Deprescribe rescue agent Don't avoid SGLT2i. But consider "stabilise then protect" when starting from HbA1c >75 mmol/mol (9.0%). Sick-day rules essential either way. 🔗 doi.org/10.1111/dom.70…

💪 Muscle-preserving therapies during #GLP1 weight loss: hype or hope? New review covers the emerging pipeline: 🔹 Bimagrumab + sema 2.4mg: 67-69% less lean mass loss 🔸 Enobosarm (SARM) in over-60s: 71% less lean mass loss 🔹 Apitegromab + tirzepatide: 55% attenuation But: 🔸 Muscle spasms in 50-64% on myostatin inhibitors 🔹 Azelaprag discontinued (liver safety) 🔸 Most trials small, short, surrogate endpoints Key question: is lean mass loss during weight loss actually a problem❓ 🟢Evidence suggests largely adaptive. 🟢Grip strength and function often improve despite LST loss. 👉Protein + resistance exercise still the evidence base. 💉Pharma add-ons coming but not yet proven for functional outcomes. 🔗 doi.org/10.1093/obendo…

I’m teaming up with @drkevinfernando for a free webinar on cardiovascular, kidney and metabolic care. This session will also mark the official launch of The CKM Collaborative, formerly CVRMUK. 📅 Thursday, April 30 | 7pm | Online 💻 Register here: tinyurl.com/3hszjs5s

Join me and @drpatrickholmes for a free webinar on cardiovascular, kidney and metabolic (CKM) care. This session will also mark the official launch of The CKM Collaborative, formerly CVRMUK. 📅 Thursday, April 30 | 7pm | Online 💻 Register here: tinyurl.com/3hszjs5s