Conference over coffee: Diabetes and obesity management in multimorbidity and frailty

Diabetes and obesity management in complexity – Physical health

Hannah Beba, Consultant Pharmacist, West Yorkshire Health & Care Partnership
Philip Newland-Jones, Consultant Pharmacist, University Hospital Southampton NHS Foundation Trust

● Diabetes and obesity drive a connected, multi-organ cluster: cardio–kidney–metabolic (CKM) syndrome.

• Visceral adiposity and insulin resistance are the drivers.
• Affects four organ domains – chronic kidney disease (CKD), cardiovascular disease (CVD), metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) and obstructive sleep apnoea (OSA).

● Multimorbidity is the rule, not the exception.

• In people with type 2 diabetes:
  • Approximately 40% have CKD.
  • Up to 70% have MASLD.
  • 2–4-times higher mortality risk.
• In people with obesity, more than two in three have sleep-related breathing disorders.

● Modern pharmacology has multi-organ effects: see Table 1.

● The evidence base is large and recent:

• 2019 to 2025 – an avalanche of practice-changing trials (see Table 2). Guidelines struggle to keep up, so understanding the trials is important for day-to-day decisions.

● Layered cardiorenal protection framework:

• Foundation: RAAS blockade (ACE inhibitor or ARB) to maximum tolerated dose; blood pressure <130/80 mmHg, glycaemic and lifestyle optimisation.
• SGLT2 inhibitor: foundational in all with albuminuric CKD; recommended by NICE for all with type 2 diabetes.
  • 39% lower risk of kidney/CVD composite in DAPA-CKD, 28% reduction in EMPA-KIDNEY and 30% reduction in CREDENCE (diabetic nephropathy only).
• Finerenone (non-steroidal MRA): add on to RAAS inhibitor +/– SGLT2 inhibitor in type 2 diabetes with diabetic nephropathy.
  • 13–18% reduction in composite outcome with finerenone in FIDELIO-DKD and FIGARO-DKD trials.
• GLP-1 receptor agonist: semaglutide has shown cardiovascular, kidney and mortality benefits:
  • FLOW trial: 24% reduction in kidney events in people with type 2 diabetes and CKD.
• Sequencing, monitoring and deprescribing are core pharmacist roles.
• Expect an initial eGFR “dip” when starting RAASi/SGLT2i/finerenone. Not a reason to stop the drugs.
• Monitor potassium carefully if prescribing finerenone.

● Weight management and the cardiovascular framework:

• Secondary prevention backbone is lipid-lowering therapy to ESC LDL targets (Mach et al, 2025):
  • Statin +/– ezetimibe/bempedoic acid/inclisiran/PCSK9 inhibitor.
• Antiplatelets.
• ACE inhibitor/ARB.
• Blood pressure control.
• Cardiac rehabilitation.
• SGLT2 inhibitor.
• GLP-1 receptor agonist: SELECT trial established obesity as a modifiable cardiovascular risk factor and its treatment as secondary prevention.
  • Semaglutide 2.4 mg versus placebo in 17,604 adults with BMI ≥27 kg/m², no diabetes, over 40 months.
  • 20% relative risk reduction in major adverse cardiovascular events (MACE); benefit largely uncoupled from weight loss magnitude (those losing <5% had same benefit as >5%).
• Tirzepatide: SUMMIT trial showed fewer cardiovascular deaths/heart failure events in obesity-related HFpEF.

● MASLD starts as a silent disease; progresses to MASH/fibrosis; increased CVD risk.

• Stratify risk: Fib-4, ELF, transient elastography scan. Identify significant fibrosis (≥F2).
• Weight loss ≥10% resolves steatohepatitis in around 90%; regresses fibrosis in around 45% (Vilar-Gomez et al, 2015).
• Statins are safe and indicated. Optimise glycaemia, blood pressure and lipids
• ESSENCE trial: 62.9% steatosis resolution in semaglutide 2.4 mg recipients versus 34.3% with placebo. 36.8% vs 22.4% fibrosis improvement.
  • Clinical outcomes to 240 weeks’ evaluated in ESSENCE 2 – results expected in 2029.

● Obstructive sleep apnoea:

• SURMOUNT-OSA 1 and 2 trials: tirzepatide 10–15 mg evaluated in people with moderate/severe OSA and obesity; with/without continuous positive airways pressure (CPAP).
  • 52 weeks: 50–63% reduction in apnoea/hypopnoea ratio versus placebo.
  • 43–51% met disease resolution criteria.
  • Reductions in blood pressure and hsCRP also seen.

● Safety, monitoring and deprescribing:

• SGLT2 inhibitors: euglycaemic diabetic ketoacidosis risk (sick day rules); mycotic infections; volume depletion; initial eGFR dip; prescribe for protective considerations.
• Finerenone: hyperkalaemia risk (potassium monitoring at baseline and 4 weeks); initiate if eGFR is ≥25 mL/min/1.73 m² and potassium ≤5.0 mmol/L; sequence after SGLT2 inhibitor, (mitigates hyperkalaemia risk).
• GLP-1 receptor agonists and tirzepatide: gastrointestinal intolerance (titrate slowly); pancreatitis risk; avoid in pregnancy; withhold around sedation/anaesthesia.
• Polypharmacy and equity: de-escalate sulfonylureas/insulin as incretins and SGLT2 inhibitors are optimised (reduce hypoglycaemia); shared decision-making and structured medication review, apply an equality lens.

Key steps to deliver effective care across all domains

● Treat the drivers – visceral fat and insulin resistance. Aim for sustained weight loss and cardiometabolic control.

● Lay foundational protection early.

● Layer disease-modifying agents by indication and residual risk.

● Treat to target: LDL-cholesterol, blood pressure, HbA_1c, weight.

● Think absolute risk and the whole person.

● Own the follow-through: monitoring, titration, deprescribing.

Type 2 diabetes and frailty

The frailty arm of NG28 – a multimorbidity-focused case discussion

Hannah Beba, Consultant Pharmacist, West Yorkshire Health & Care Partnership

● Frailty is more prevalent and develops earlier in people with type 2 diabetes compared to those without.

● Most frail older adults with diabetes live with multiple long-term conditions – heart failure, chronic kidney disease, cardiovascular disease, cognitive impairment.

• The resulting polypharmacy, hypoglycaemia and adverse drug events drive falls, admissions and reduced quality of life.
• Function, independence and harm avoidance may matter more than glycaemic or end-organ targets.

● This is reflected in the frailty arm of the NICE NG28 guideline – but treat the person, not the algorithm.

• Offer modified-release metformin as the first line; add SGLT2 inhibitor only if safe (consider volume depletion, hypotension risks).
• If metformin MR unsuitable, consider whether SGLT2 inhibitor monotherapy is safe; otherwise, consider DDP-4 inhibitor monotherapy.
• GLP-1 receptor agonists and tirzepatide are permitted, but individualise and offer if relevant indication.
  • Weight loss includes lean mass loss – protect muscle and function.
• When several conditions compete, use shared decision-making.
  • Prioritise which to treat; consider treatment burden and potential harm.
  • Aim for function, independence, symptom control and quality of life.
  • Aim for smallest effective number of medicines at lowest effective dose.

● NICE’s NG28 cardiorenal shift is based on cardiovascular, heart failure and renal randomised controlled trials:

• People with multiple long-term conditions (especially severe frailty, dementia, care home residence) were under-represented.
• Some trials demonstrated persistent benefit in older/frail. For example, in DELIVER, dapagliflozin reduced heart failure admissions and cardiovascular death across the frailty strata; most frail gained largest absolute benefit and quality of life improvement.
  • But harm scales too, hence caution with SGLT2 inhibitors.
• Relax targets: Sulfonylureas and insulin drive hypoglycaemia and harm; favour low-hypo-risk agents (e.g. DPP-4 inhibitors); increased mortality in ACCORD trial with intensive control (long-duration type 2 diabetes).

Note, the right medicine for the disease can be the wrong medicine for the person.

NICE resources

• NG28: Type 2 diabetes in adults
• NG56: Multimorbidity
• NG197: Shared decision making

Obesity management in the frail patient population

Satish Durgam, GPwER diabetes, obesity and metabolic health, London

● Improving care for older people living with frailty or multiple long-term conditions is a priority in the 10 Year Health Plan for England.

● Sarcopenic obesity: defined as increased adipose tissue with concurrent decline in muscle mass (quality and/or quality) and function.

• Poses a major health risk.

● Geriatric assessment of older adults with obesity helps identify those at risk, so that tailored nutrition and activity can be recommended and appropriateness of medication can be considered (Dewar, 2025):

• Cognitive function – mini mental score/three-item recall.
• Functional status – hand grip strength, activities of daily living (ADL).
• Mobility/balance – falls, challenges in walking/rising from chair.
• Psychosocial assessment – PHQ-9/GAD-7 questionnaires.
• Social determinants of health – consider housing, food insecurity, transportation.

● Obesity paradox – overweight and obesity seem protective against disease and mortality in older adults – but this is not a reason not to manage obesity.

● Tailored and personalised weight loss intervention is recommended for older adults with obesity, weight maintenance for those with overweight but no comorbidities.

● Key approaches (Dewar, 2025):

• Consider the risks and benefits of treatment alongside the person’s priorities.
• Prioritise independence and quality of life – not weight reduction alone.
• Use waist circumference, grip strength and gait speed to detect sarcopenic obesity.
• Optimise protein intake and calorie consumption to prevent falls.
• Communication is important – avoid stigmatisation, which is common.
• Use a tailored, personalised approach considering racial, ethnic and systemic disparities.

● There is a need (often unmet) to consider the cumulative weight-promoting effects of medications:

• Diabetes medications.
• Beta-blockers.
• Antidepressants.
• Atypical antipsychotics.
• Corticosteroids.
• Anticonvulsants.
• Neuropathic pain medications.
• First-generation antihistamines.

● When to consider lifestyle, pharmacological and surgical interventions: see Figure 1 (Henney et al, 2025).

Useful review

• Brown MB (2026) Take a personalised approach to weight management for older adults with obesity. Drugs Ther Perspect 42: 56–60