Obesity, MASLD and inflammation; the proactive clinic; special populations
Obesity as a chronic disease and the cardiovascular case for treating it, the anti-obesity toolkit with its NICE appraisals, the MASLD pathway from FIB-4 to the root cause, inflammation as the fifth pillar, the proactive cardiorenal-metabolic clinic with its case-finding triad and three-visit cycle, and the populations where the ladder bends: women and the menopause, pregnancy, frailty, advanced CKD, testosterone deficiency and cancer survivorship. About 60 minutes, for GPs, GP trainees, pharmacists, nurses, advanced clinical practitioners and physician associates. A 10-item knowledge check is marked on our learning platform; pass at 70% and a numbered, verifiable Certificate of CPD (1 hour) from New Vision University (UK) is issued to you.
Living Certificate · reviewed and kept current
Last editorial review: awaiting clinical sign-off · Next scheduled refresh: 12 months after sign-off.
The Golden Triangle for the topic taught here: fixed to the topic, and re-examined when its knowledge, evidence or real-world sources change.
Golden Triangle
Obesity
Knowledge Green · Evidence Green · Real-world Red
Not yet at the Equinox · UK (NHS England) · as of 7 October 2026 · How the triangle works
A 46-year-old woman with "a bit of fatty liver"
Mrs S, 46, is told after an ultrasound for unrelated pain that she has "moderate fatty change in the liver" and that "it's common, don't worry". She is teetotal. BMI 34, waist-to-height ratio 0.61, BP 138/86, HbA1c 44 mmol/mol, ALT 62 U/L, AST 67, platelets 240; total cholesterol 5.6, HDL-C 1.0, triglycerides 2.0 mmol/L. QRISK3 is 4%.
The CVRM-HF clinic sees a different patient: clinical obesity with central adiposity, prediabetes, high-normal blood pressure (138/86: below the NICE NG136 diagnostic threshold of 140/90, so not hypertension in UK terms, but stage 1 on the ACC/AHA 130–139/80–89 scale that CKM staging uses, with a CKM goal below 130/80), an atherogenic lipid profile, and MASLD, the liver expression of the same disease. Her FIB-4 is 1.63, indeterminate, so elastography is arranged: 7.4 kPa, low fibrosis risk, to be repeated in three years, sooner if her metabolic risk rises. The root cause is treated: a structured weight-management programme with a 7–10% target, an ACR (2 mg/mmol), Lp(a) once (40 nmol/L), home blood pressure monitoring and lifestyle, aiming for the CKM goal below 130/80 (NG136 does not diagnose hypertension below a clinic reading of 140/90, so drug treatment would not be started at this level), and a conversation about semaglutide through the specialist weight-management service (NICE TA875: BMI 30–34.9 with a weight-related comorbidity if she meets the NG246 referral criteria; within the service and for a maximum of two years). At BMI 34 she sits below the TA1026 threshold of 35 for tirzepatide (32.5 in the lower-threshold ethnic groups), and prediabetes is not one of the conditions NHS England counts for the phased primary-care roll-out. At six months she has lost 8%; the ALT is 31 and the HbA1c 41. Nothing was "a bit of" anything. Obesity as the disease, MASLD as its liver, inflammation as the thread, a clinic that finds and keeps these patients, and the populations where the ladder bends: this module.
By the end of this module you will be able to…
Obesity is a chronic disease
Pre-clinical and clinical obesity, how NICE NG246 measures adiposity, and the trial that made weight loss cardiovascular medicine.
The Lancet Diabetes & Endocrinology Commission (2025) defined clinical obesity as a chronic, systemic illness (excess adiposity with measurable harm to organ function or daily activities) and pre-clinical obesity as excess adiposity with preserved organ function: a state of increased risk that warrants monitoring and, where appropriate, risk-reducing intervention, not a disease or a predisease state. NICE NG246 has not adopted this framework: it still classifies adults by BMI class (with lower thresholds for some ethnic groups) and waist-to-height ratio, and that is what UK eligibility rules use; the AACE/ACE 2016 guideline's complication-centred staging of adiposity-based chronic disease anticipated the Commission's approach. This module uses the Commission's phenotypes as its clinical frame. About one in four UK adults (around 14 million, of whom fewer than a quarter are diagnosed) has MASLD, about 30% worldwide, rising to about two-thirds of people with type 2 diabetes; inflammation is the thread that links obesity, the liver and the vessel wall.
Measuring adiposity (NICE NG246)
BMI together with waist-to-height ratio: 0.5 or more indicates increased central adiposity, 0.6 or more high. Lower BMI thresholds (23 overweight, 27.5 obesity) for South Asian, Chinese, other Asian, Middle Eastern, Black African and African-Caribbean groups. Record both, and the consequences: blood pressure, HbA1c, lipids, ACR, liver enzymes, sleep apnoea symptoms, osteoarthritis, mood.
The cardiovascular case: SELECT and TA1152
SELECT (Lincoff, NEJM 2023; n = 17,604): semaglutide 2.4 mg weekly reduced major adverse cardiovascular events by 20% in adults with obesity or overweight (BMI ≥ 27) and established cardiovascular disease without diabetes. NICE TA1152 (May 2026) recommends semaglutide 2.4 mg to reduce major adverse cardiovascular events in adults with BMI 27 or more and established cardiovascular disease, defined as previous myocardial infarction, previous stroke or symptomatic peripheral arterial disease; SELECT enrolled people without diabetes, but neither NICE nor the licence excludes people with diabetes. It is separate from the weight-management appraisal. Anti-obesity pharmacology is now secondary-prevention pharmacology.
Checkpoint 1 · South Asian woman, BMI 27.5, waist-to-height ratio 0.59, no diagnoses. Classification?
Obesity for her ethnic background with increased central adiposity (0.59; NG246 calls 0.6 or more high). Offer the weight-management conversation and screen for the consequences (HbA1c, lipids, blood pressure, ACR, liver enzymes).
Anti-obesity pharmacology, even-handedly
Every UK-licensed agent, its evidence, its NICE position, and the rules that go with a prescription.
| Agent | Class · key trial · typical weight loss | UK position |
|---|---|---|
| Orlistat | Lipase inhibitor · XENDOS · about 3% additional | NG246 Table 1 (no NICE appraisal): BMI ≥ 30, or ≥ 28 with associated risk factors (SmPC); any setting, lower dose from pharmacies; stop if < 5% loss at 12 weeks. Modest efficacy; gastrointestinal effects (XENDOS) |
| Liraglutide 3 mg daily | GLP-1 receptor agonist · SCALE · about 8% (5–6% beyond placebo) | TA664 (December 2020, adults only): BMI ≥ 35 (≥ 32.5 in the lower-threshold groups) with non-diabetic hyperglycaemia and high cardiovascular risk; prescribed in secondary care by a specialist tier 3 weight-management service; TA664 covers adults only, and adolescent use is a licensed indication in the Saxenda SmPC; stop if less than 5% loss after 12 weeks on 3 mg (SmPC) |
| Semaglutide 2.4 mg weekly | GLP-1 receptor agonist · STEP-1/4 about 15% · SELECT 20% fewer major events | TA875 (weight management, specialist services, two-year stop rule); TA1152 (cardiovascular risk reduction with established CVD: previous MI, stroke or symptomatic PAD; BMI ≥ 27) |
| Tirzepatide 5–15 mg weekly | Dual GIP/GLP-1 · SURMOUNT-1 about 21% · SURMOUNT-2 in type 2 diabetes | TA1026: BMI ≥ 35 with a weight-related comorbidity (thresholds lowered by 2.5 for the ethnic groups above); NHS primary-care access phased by BMI and number of qualifying conditions (hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, type 2 diabetes) from June 2025 over an initial three years (cohorts to 2028/29), within a 12-year maximum set by NICE (NHS England interim commissioning guidance, April 2026) |
| Naltrexone–bupropion | Combination · COR trials · about 5% | Licensed in the UK (Mysimba); NICE TA494 (2017): not recommended for NHS use; available privately |
| Setmelanotide | MC4R agonist · genetic obesity (POMC, LEPR, PCSK1 deficiency; Bardet-Biedl) | NICE HST21 (2022): POMC, PCSK1 or LEPR deficiency from age 6; HST31 (2024): Bardet-Biedl syndrome only if treatment starts at 6–17 years; highly specialised genetic obesity services only |
The rules that go with the prescription. Pharmacotherapy sits on a reduced-calorie diet, activity and behavioural support, with a defined review: for semaglutide consider stopping if less than 5% of initial weight has been lost after six months of treatment (TA875), and for tirzepatide decide whether to continue if less than 5% has been lost after six months on the highest tolerated dose (TA1026); liraglutide 3 mg and orlistat are stopped if less than 5% is lost after 12 weeks on the full dose (SmPC rules, as tabulated in NG246). Counsel on nausea, gallstones, pancreatitis (new persistent abdominal pain means lipase and imaging), dehydration, and contraception (oral contraceptive absorption with tirzepatide). Reduce sulfonylurea and insulin doses in diabetes (F3). Plan for the end of treatment: weight regain is the rule without maintenance, which is why the behavioural foundation matters. Referral for bariatric assessment is offered at BMI 40 or more, or 35–39.9 with a significant weight-related condition (referral is considered at thresholds 2.5 lower for the listed ethnic groups, NG246 1.18.2), through a specialist overweight and obesity management service, with expedited assessment at BMI 35 or more and type 2 diabetes diagnosed within 10 years (NG246 1.18.1–1.18.3); surgery remains the most durable option.
Checkpoint 2 · BMI 41, hypertension, dyslipidaemia, sleep apnoea, type 2 diabetes, lifestyle programme completed. Tirzepatide?
Eligible under NICE TA1026 (BMI ≥ 35 with a weight-related comorbidity; she has four of the five conditions NHS England counts), through the phased NHS primary-care route with diet, activity and behavioural support. No need to fail liraglutide first.
MASLD: the primary-care pathway
Who to screen, FIB-4 with age-banding, the second-line tests, and treating the root cause.
MASLD (formerly NAFLD) is hepatic steatosis plus at least one cardiometabolic risk factor; MASH is the inflammatory subset. What matters is fibrosis stage: mortality rises with stage (all-cause hazard ratios of roughly 1.5 at F2, 2 at F3 and 3.7 at F4 versus no fibrosis, and liver-related mortality about 4-, 8- and 15-fold; Ng et al., Clin Gastroenterol Hepatol 2023), from liver and cardiovascular causes alike. The practical UK pathway (Robb, Ravindran and Varma, InnovAiT 2026; BSG/BASL 2022; EASL–EASD–EASO 2024; NICE NG49) has five steps.
Checkpoint 3 · Steatosis on ultrasound, BMI 34, prediabetes, FIB-4 1.63. Next test?
Indeterminate FIB-4: transient elastography or ELF; refer if liver stiffness is 12 kPa or more (EASL 2024; AHA/ACC/ADA/ASN 2026) or ELF is 10.51 or more (NICE NG49); many UK pathways act at liver stiffness above 8 kPa or ELF above 9.5–9.8. Not biopsy, not watchful waiting; weight management starts now.
Inflammation, and the clinic that catches and changes the disease
The fifth pillar, the case-finding triad, the three-visit cycle, lifestyle as disease-modifying therapy, and the behaviour-change skills that make it stick.
Inflammation as the fifth pillar. CANTOS proved the inflammatory hypothesis of atherosclerosis; LoDoCo2 and COLCOT turned it into a usable drug, low-dose colchicine 0.5 mg daily for established atherosclerotic disease, endorsed by DCRM 2.0 and a Class IIa (Level A) should-be-considered recommendation in the ESC 2024 chronic coronary syndromes guideline; the trials and guidelines do not require a raised hsCRP, although hsCRP of 2 mg/L or more despite lipid lowering marks residual inflammatory risk. It remains unlicensed for this in the UK (F1, Lesson 5). Measure hsCRP (and ACR) with the lipid profile where risk is unclear (borderline or intermediate 10-year risk) or in established disease with events despite optimal lipid and blood-pressure control (DCRM 2.0); interpret only without an acute cause.
The proactive clinic
Every cornerstone document, DCRM 2.0, the 2026 CKM guideline and the cardiorenal-metabolic call to action for primary care (Säemann et al., 2025), makes the same point: organ-protective drugs work best inside a proactive, lifestyle-anchored clinic that finds high-risk people early and keeps them engaged. The GP is the central coordinator; around the hub sit nursing, pharmacy, dietetics and rapid links to cardiology, nephrology, diabetes and weight-management services.
V1 · Detect and baseline
Case-find with the triad: eGFR, urine ACR, NT-proBNP (the AHA/ACC/ADA/ASN guideline makes natriuretic-peptide testing a class 2a recommendation for adults with a 10-year PREVENT-HF risk of 5% or more, so direct NT-proBNP at that group); stage on the CKM continuum; record the core numbers (BP, lipids or ApoB, HbA1c, eGFR and ACR, weight and waist); give the patient a held cardiometabolic summary; agree two or three SMART goals.
V2 · Activate and titrate (6–12 weeks)
A motivational-interviewing review of progress; titrate organ-protective therapy; recheck eGFR, ACR and potassium where an agent was started.
V3 · Consolidate and sustain (about 6 months)
Confirm targets and any change in CKM stage; embed self-management; set the recall and digital follow-up cadence, sooner if eGFR or ACR is worsening.
Lifestyle is disease-modifying: Life's Essential 8
The 2026 CKM guideline makes lifestyle modification to lose at least 5–10% of baseline weight, delivered through intensive programmes that include at least 150 minutes a week of moderately vigorous aerobic activity, a class 1 first-line recommendation because it promotes stage regression, not merely slower progression. Four behaviours (eat better: Mediterranean or DASH; be more active; quit tobacco and nicotine; sleep 7–9 hours, the Life's Essential 8 target from 2022) and four factors (manage weight; control cholesterol: ApoB and LDL-C; manage blood glucose; manage blood pressure below 130/80).
Motivational interviewing
A collaborative, guiding style rather than advice-giving: engage, focus, evoke, plan. Open questions, affirmations, reflective listening and summaries; roll with resistance; listen for change talk and support the patient's own reasons. Fidelity predicts behaviour change better than information does.
SMART goals and decision aids
Two or three specific, measurable, achievable, relevant, time-bound goals the patient chooses, reviewed at V2 with one primary outcome they can see move. A patient-held summary with an intuitive overall-risk indicator reframes "abnormal results" as "something I can change"; portals and apps return results in plain language and prompt reviews between visits.
Checkpoint 4 · The one cheap screen to run on the high-risk register?
eGFR, urine ACR and NT-proBNP: kidney function, the earliest cardiorenal signal and gate for SGLT2 inhibitors and finerenone, and pre-clinical heart failure. On a high-risk register, direct NT-proBNP (with hs-troponin) at adults with a 10-year PREVENT-HF risk of 5% or more (AHA/ACC/ADA/ASN 2026, class 2a).
Where the ladder bends: special populations
Women and the menopause, pregnancy and preconception, frail older adults, advanced CKD, testosterone deficiency, cancer survivorship.
Women and the menopause
Women are less likely than men to be prescribed a statin, ACE inhibitor or SGLT2 inhibitor at every level of risk. The menopause is a cardiometabolic inflection: visceral fat redistribution, falling SHBG, rising LDL-C, triglycerides and ApoB, insulin resistance and blood pressure; the odds of metabolic syndrome are about 3.5 times higher after the menopause (Hallajzadeh et al., Menopause 2018), and frequent vasomotor symptoms are associated with incident cardiovascular disease (Armeni et al., Maturitas 2023). Precision menopause (Ravindran and Varma, InnovAiT 2026): re-stage risk (QRISK3, ApoB, Lp(a) once, ACR) and intensify prevention; use HRT (transdermal oestradiol with micronised progesterone, started within ten years of the menopause or before 60) for symptoms; NICE NG23 says not to offer HRT for primary or secondary prevention of cardiovascular disease, prefers transdermal HRT where VTE risk is raised (including BMI over 30), and advises that for women with a history of coronary heart disease or stroke, HRT is discussed with and offered, if appropriate, by a professional with menopause expertise.
Pregnancy and preconception
Before conception, aim for HbA1c below 48 mmol/mol if achievable without problematic hypoglycaemia; stop statins, ACE inhibitors, ARBs and all non-metformin oral glucose-lowering agents (NICE NG3); stop SGLT2 inhibitors, GLP-1 receptor agonists and tirzepatide in line with their SmPCs; metformin or insulin; folic acid 5 mg; refer to the joint clinic at planning or diagnosis. Nephropathy and retinopathy can worsen in pregnancy. Restart agents postpartum according to feeding. Contraception advice is part of every weight-management or diabetes prescription for women of childbearing age.
Frail older adults and advanced CKD
Clinical frailty score 6 or more drives deliberate de-escalation: HbA1c up to 64 mmol/mol, deprescribe sulfonylureas, review polypharmacy quarterly (anticholinergic burden, bleeding, nutrition), SGLT2 inhibitor caution with BMI under 25 or dehydration risk, statins retained for secondary prevention if life expectancy exceeds a year. In CKD G4–G5: SGLT2 inhibitor continued to dialysis once started, metformin stopped below 30, finerenone avoided below eGFR 25 or potassium above 4.8, insulin the safest glucose-lowering agent, statins not started on dialysis (4D, AURORA).
Testosterone deficiency and cancer survivorship
Testosterone deficiency is tightly bound to visceral obesity, type 2 diabetes and CKD (BSSM 2023 advises screening men with type 2 diabetes, BMI over 30 or waist over 102 cm; the EAU tests symptomatic men and assesses cardiovascular risk first): confirm with two morning (7–11 am) samples, adding LH and FSH, SHBG or free testosterone if borderline, and prolactin if LH and FSH are low; treat confirmed symptomatic deficiency in conjunction with, not after, weight and glycaemic optimisation. TRAVERSE (NEJM 2023) showed cardiovascular non-inferiority with more atrial fibrillation, pulmonary embolism and acute kidney injury. Cancer survivors (anthracyclines, trastuzumab, androgen deprivation) carry extra cardiometabolic risk: statin and blood-pressure control as standard, and surveillance for cardiomyopathy and arrhythmia (ESC cardio-oncology 2022).
Checkpoint 5 · 52-year-old with hot flushes, 6 kg central weight gain, rising LDL-C and blood pressure: "Will HRT protect my heart?"
Re-stage her risk and intensify prevention; offer HRT for the symptoms (transdermal oestradiol with micronised progesterone, within the window), not as cardioprotection.
Running it: the searches and the recall system
Digital phenotyping at practice scale, and the three searches that feed the clinic.
Digital phenotyping. In a study of a primary care population of 10,306 adults (Mathieson, Simmonds-Rosten, Shuker, Yang and Varma, "Digital phenotyping and additive multimorbidity scoring to operationalise very-high-risk secondary prevention in primary care", ESC Congress 2026, abstract 84246), a single search for established atherosclerotic disease with LDL-C above target identified about 1.7% of the list, and an additive cardiorenal-metabolic care-gap score (points for diabetes, hypertension, CKD and obesity) ranked who needed review first, turning opportunistic case-finding into systematic, auditable recall.
Three searches
The found patients get a held summary, two or three goals and a V2 date. The clinic's numbers (patients staged, moved down a stage, at target) are the practice's quality-improvement evidence and the institutional-licence report.
Practice task
Run search 3 this week: count the patients with type 2 diabetes or BMI ≥ 30 (a first-pass cut-off; the pathway threshold is BMI 25) who have no FIB-4 in three years, and calculate FIB-4 for the first twenty from existing results. Record the number and what you found in the reflection box below; it prints on your certificate.
Checkpoint 6 · Which search turns opportunistic case-finding into systematic recall?
The care-gap score: atherosclerotic disease with LDL-C above target, scored additively for diabetes, hypertension, CKD and obesity, recalled from the top.
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New Vision University (UK)
Acumen Focus · CVRM-HF Foundation series · delivered by MD Acumen Ltd
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Acumen Focus F6 · Obesity, MASLD and inflammation; the proactive clinic; special populations
including its 10-item knowledge check
Authored by Prof Rajesh Varma · MD Acumen Ltd · mdacumen.com
CPD authorised by Prof Rajesh Varma, Convenor for CPD, New Vision University (UK)
Signed against: NICE NG246 · NICE NG49 · NICE TA875 / TA1026 / TA664 / TA1152 · NICE NG23 · NICE NG3 · Lancet Commission 2025 · AHA/ACC/ADA/ASN CKM guideline 2026 · SELECT (2023) · TRAVERSE (2023) · BSSM 2023 · InnovAiT 2026 (Robb et al.; Ravindran and Varma) · Säemann 2025 · DCRM 2.0 (2024)
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Keep learning
F6 completes the CVRM-HF Foundation series (F1 cardiometabolic risk · F2 lipids · F3 type 2 diabetes · F4 heart failure · F5 kidney disease · F6 obesity and MASLD). Complete all six for the series certificate (6 CPD); how the series is credited towards the Certificate of Advanced Studies in CVRM-HF is set out on the programme page.
Key sources
Every clinical statement in this module is checked against the source below at each signed review. Where several licensed agents in a class exist they are presented even-handedly per their NICE technology appraisals.
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