T2dm Comorbidity Medicine Selector

Type 2 Diabetes — Comorbidity-Stratified Medicine Selection

Based on: Type 2 Diabetes in Adults: Management (NG28) — NICE (last updated February 2026) Reference: https://www.nice.org.uk/guidance/ng28

PURPOSE

Use this skill when initiating or intensifying glucose-lowering treatment in an adult with type 2 diabetes. The NICE NG28 framework stratifies medicine choice by the person's comorbidity profile rather than a single universal algorithm. This skill identifies the correct comorbidity category, maps it to the guideline-recommended initial regimen, and specifies when and how to add further medicines if glycaemic targets are not met.

STEP 1 — GATHER INFORMATION

Collect the following before selecting a medicine regimen:

Glycaemic status

• Current HbA1c (mmol/mol and %)
• Individualised HbA1c target already agreed (or needs agreeing — see NICE NG28 Section 1.5)
• Current glucose-lowering medicines (drug, dose, duration, tolerability)
• Duration since diagnosis

Comorbidity screen — ask and document each:

• Heart failure? (any ejection fraction)
• Established atherosclerotic cardiovascular disease (ASCVD)? (coronary artery disease, stroke, peripheral arterial disease)
• Early onset type 2 diabetes? (defined by NICE as diagnosis before age 40)
• Obesity? (BMI ≥30 kg/m², or ≥27.5 kg/m² in South Asian / Black African or Caribbean groups)
• Chronic kidney disease (CKD)? If yes: current eGFR (ml/min/1.73 m²)
• Frailty? (if suspected, confirm with validated frailty assessment before prescribing)

Safety parameters

• eGFR — essential for metformin and SGLT-2 inhibitor dosing and contraindications
• Risk factors for diabetic ketoacidosis (DKA): previous DKA, intercurrent illness, very low carbohydrate / ketogenic diet, dehydration
• Hypoglycaemia risk: driving / machinery, fall risk, impaired hypoglycaemia awareness
• Current use of DPP-4 inhibitor (incompatible with GLP-1 receptor agonists / tirzepatide)
• Pregnancy status or intent (separate guidance applies)

Patient factors

• Preference regarding injection vs oral route
• Adherence concerns or previous intolerances
• Weight trajectory and weight target

STEP 2 — RULE IN / RULE OUT

Confirm this skill applies:

• Adult with confirmed type 2 diabetes (if treatment response is atypical, revisit diagnosis per NICE NG17 on type 1 diabetes)
• Decision point is initiation or intensification of glucose-lowering medicine

Immediate escalation — do not use this skill as the primary action if:

• Hyperglycaemic emergency (DKA, hyperosmolar hyperglycaemic state) → emergency pathway
• HbA1c ≥75 mmol/mol (9.0%) on no treatment → consider combination basal insulin + oral agents from the outset (see Section 1.33.2)
• Intercurrent acute illness → sick day rules apply first (Section 1.10); defer medicine changes until stable

Contraindication checks before proceeding:

• Metformin is contraindicated if eGFR <30 ml/min/1.73 m²
• Most SGLT-2 inhibitors should not be initiated if eGFR <30 ml/min/1.73 m² (dapagliflozin and empagliflozin have specific lower thresholds — check SPC)
• GLP-1 receptor agonists / tirzepatide must NOT be combined with a DPP-4 inhibitor
• Pioglitazone is contraindicated in heart failure

Multiple comorbidities: If the person has more than one listed comorbidity (e.g. ASCVD and CKD), make a shared decision taking into account contraindications, relative benefits, and patient preference per Section 1.9.3.

STEP 3 — CLASSIFY OR STRATIFY

Identify the person's primary comorbidity profile from the six NICE categories. If multiple apply, see the note on multiple comorbidities in Step 2.

STEP 4 — DECIDE

INITIAL MEDICINE REGIMEN (first prescription)

Stepwise introduction: Start metformin first, titrate to maximum tolerated dose, then add SGLT-2 inhibitor; if GLP-1 receptor agonist or tirzepatide is part of the plan, add after SGLT-2 inhibitor is at maximum tolerated dose.

FURTHER MEDICINES (HbA1c not at target on initial regimen)

Trigger: HbA1c rises to ≥58 mmol/mol (7.5%) on current treatment — reinforce lifestyle advice, confirm adherence, then intensify medicines.

INSULIN-BASED TREATMENT (when indicated across any profile)

• Offer basal insulin (once or twice daily) as initial insulin therapy
• If HbA1c ≥75 mmol/mol (9.0%), consider combining basal + short/rapid-acting insulin from the outset
• Continue metformin on starting insulin; stop other medicines used solely for glycaemia
• Continue SGLT-2 inhibitors if retained for cardiovascular or renal benefit — reassess DKA risk
• Provide structured education: injection technique, self-monitoring, dose titration, hypoglycaemia management, DVLA requirements

STEP 5 — CLINICAL GUARDRAILS

Common Mistakes

• Giving the same regimen to everyone: The NICE 2026 update specifically differentiates initial medicines by comorbidity — a single universal algorithm no longer applies. The most common error is starting metformin alone as the first-line treatment across all profiles.
• Missing ASCVD at initiation: Patients with established coronary artery disease, prior stroke, or peripheral arterial disease qualify for triple therapy from the outset (metformin + SGLT-2 + semaglutide). Failing to identify ASCVD leads to undertreatment.
• Combining GLP-1 receptor agonist / tirzepatide with a DPP-4 inhibitor: These should never be prescribed together — the guideline explicitly prohibits this combination (Section 1.24.6).
• Continuing SGLT-2 inhibitors in frail patients at risk of falls: Volume depletion and hypotension are real risks in frail older adults. Frailty assessment should precede prescribing, not follow it.
• Not reassessing SGLT-2 inhibitor suitability as eGFR declines: An SGLT-2 inhibitor that was appropriate at eGFR 45 may be contraindicated when eGFR falls below 30. Monitor and review at each visit.
• Stopping SGLT-2 inhibitors when glycaemic target is reached: The guideline states they should be continued for cardiovascular and renal protection even if glycaemic contribution is minimal (Section 1.24.2).
• Prescribing pioglitazone in heart failure: Pioglitazone is contraindicated in heart failure due to fluid retention risk — it appears in further medicine options for several profiles but must be excluded for the heart failure group.

Mimics and Diagnostic Traps

• Latent autoimmune diabetes in adults (LADA): Can present identically to type 2 diabetes in adults aged 30–50. Consider if: rapid deterioration on oral agents, low BMI, personal or family history of autoimmune disease, unexplained DKA. Check GAD antibodies and C-peptide.
• Monogenic diabetes (MODY): Consider in young adults with a strong family history and mild, stable hyperglycaemia — particularly if their treatment response to oral agents is unusually good or poor. Genetic testing changes management significantly.
• Steroid-induced hyperglycaemia: Requires a separate management approach — capillary blood glucose monitoring is indicated, and glucose patterns differ (predominantly postprandial). Do not apply standard T2DM targets.

What NOT To Do

• Do NOT prescribe GLP-1 receptor agonist / tirzepatide + DPP-4 inhibitor together — no additive benefit and guideline-prohibited
• Do NOT start a ketogenic or very low carbohydrate diet without suspending the SGLT-2 inhibitor — euglycaemic DKA risk (Section 1.21.3)
• Do NOT initiate SGLT-2 inhibitors in an unwell, dehydrated, or perioperative patient — DKA risk
• Do NOT use sulfonylureas as initial therapy in patients who drive or operate machinery without discussing hypoglycaemia risk and DVLA implications
• Do NOT apply adult targets to pregnancy — refer to NICE guideline on diabetes in pregnancy

Special Populations

• Older adults / frailty: Consider deprescribing — the smallest effective number of medicines at the lowest effective dose is the explicit NICE recommendation for frail patients. Relax HbA1c targets on a case-by-case basis.
• CKD: Dose adjustments are required across all drug classes — refer to the SPC for each product. Avoid nephrotoxic combinations. Involve pharmacy or nephrology for complex regimens.
• Ethnicity: Obesity thresholds differ — BMI ≥27.5 kg/m² triggers the obesity profile for South Asian, Black African, and Black Caribbean patients.
• Early onset T2DM (diagnosis <40 years): This group typically has a more aggressive disease course, greater insulin resistance, and is more likely to need triple therapy early. GLP-1 receptor agonists and tirzepatide are specifically considered from initiation.
• Pregnancy / childbearing potential: GLP-1 receptor agonists and tirzepatide require specific counselling. SGLT-2 inhibitors are contraindicated in pregnancy. Metformin may be continued in pregnancy under specialist guidance. Refer to NICE NG3 on diabetes in pregnancy.
• Reproductive health: When discussing GLP-1 receptor agonists and tirzepatide with women, trans men, and non-binary people of childbearing potential, follow MHRA guidance on these agents and pregnancy risk (Section 1.9.4).

SOURCE

National Institute for Health and Care Excellence. Type 2 Diabetes in Adults: Management (NG28). London: NICE; 2015, last updated February 2026. Available from: https://www.nice.org.uk/guidance/ng28