Nota Medik
T2DM Targets: HbA1c, LDL & BP - Meds, Escalation, De-escalation, Usual Doses
Contents
- Targets at a glance
- Hypertension
- BP target
- Choosing BP drugs
- BP escalation
- BP de-escalation
- Antihypertensive doses
- Diabetes mellitus
- HbA1c target
- Starting treatment by HbA1c
- Choosing by patient profile
- Glycaemic escalation
- Insulin: start and titrate
- Glycaemic de-escalation
- Glucose-lowering drug doses
- GLP1-RA doses
- Dyslipidaemia
- LDL-C target
- Choosing lipid drugs
- Lipid escalation
- Lipid de-escalation
- Statin doses by intensity
- Sources
Every T2DM follow-up clinic comes down to the same three numbers: HbA1c, LDL-C and BP. Below is a recap based on the CPG Management of T2DM (6th Edition, 2020). Antihypertensive doses come from the CPG Management of Hypertension (5th Edition, 2018).
Targets at a glance
| Parameters | Levels | |
|---|---|---|
| Glycaemic control | Fasting or pre-prandial | 4.4-7.0 mmol/L |
| Post-prandial (≥90 min after meals) | 4.4-8.5 mmol/L | |
| HbA1c | <7.0% (for most); ≤6.5% in selected patients (see Diabetes mellitus) | |
| Lipids | Triglycerides | ≤1.7 mmol/L |
| HDL-C | Male: >1.0 mmol/L; Female: >1.2 mmol/L | |
| LDL-C | ≤2.6 mmol/L; <1.8 high risk, <1.4 very high risk (see Dyslipidaemia) | |
| BP | 130-139 / 70-79 mmHg | |
| Exercise | 150 minutes/week | |
| Body weight | If overweight or obese, aim for up to 10% weight loss in 6 months | |
Adapted from Table 3-5, CPG T2DM 2020. Table 3-27 gives the female HDL-C target as >1.3 mmol/L.
Hypertension
BP target
- Start drugs when BP is persistently ≥140 systolic and/or ≥90 diastolic. There is no CV benefit from treating BP of 130-139/80-89.
- Target SBP 130-139 mmHg, DBP 70-79 mmHg.
- SBP <130 (if tolerated, but not <120) for patients without pre-existing CHD who are at higher risk of stroke or DKD.
- DBP not <70. Going too low in patients with CAD gives a J-curve.
Choosing BP drugs
- ACEi or ARB first line. Use an ACEi first; switch to an ARB if the ACEi is not tolerated (e.g. cough).
- Add-ons: CCB, diuretic, β-blocker or peripheral α-blocker.
- Most patients need several drugs: 90% need 3 to reach target.
- Never combine an ACEi with an ARB.
| Diuretics | β-blockers | ACE inhibitors | CCB | Peripheral α-blockers | ARB | |
|---|---|---|---|---|---|---|
| T2DM without nephropathy | + | +/- | +++ | + | +/- | ++ |
| T2DM with nephropathy | ++ | +/- | +++ | ++ | +/- | +++ |
Adapted from Table 3-25, CPG T2DM 2020: + to +++ = increasing evidence and/or accepted practice; +/- = use with care.
BP escalation
- Titrate the ACEi/ARB to the maximum recommended dose (for BP and anti-proteinuric effect).
- Add a CCB or diuretic, then a third agent.
- Check creatinine and K⁺ before starting and within 2 weeks after.
BP de-escalation
- Step-down is discouraged in the vast majority of patients; most stay on treatment life-long. If the patient insists, all of these must apply first:
- BP no higher than stage 1 (mild) hypertension with low global CV risk
- BP well controlled for at least 1 year on the same drugs at the same doses
- Agrees to follow-up at least 3-6 monthly
- Motivated to adopt healthy living
- Reduce or stop the ACEi/ARB (after excluding other causes) if, within 2 months of starting: creatinine stays ≥30% above baseline, eGFR falls ≥25%, or K⁺ is ≥5.6 mmol/L.
- Elderly: relax the BP target with frailty: <140/90 for healthy and complex/intermediate, <150/90 for very complex/poor health (Table 6-2).
Antihypertensive doses
Starting → maximum daily dose.
| Class | Drug | Start | Max |
|---|---|---|---|
| ACEi | Perindopril | 4 mg (erbumine) / 5 mg (arginine) OD | 8 mg / 10 mg OD |
| Enalapril | 10 mg OD | 40 mg daily | |
| Lisinopril | 10 mg OD | 80 mg daily | |
| Ramipril | 2.5 mg OD | 10 mg daily | |
| Captopril | 25 mg BD | 50 mg TDS | |
| ARB | Losartan | 50 mg OD | 100 mg OD |
| Telmisartan | 40 mg OD | 80 mg OD | |
| Valsartan | 80 mg OD | 320 mg OD | |
| Irbesartan | 150 mg OD | 300 mg OD | |
| Candesartan | 8 mg OD | 32 mg OD | |
| Olmesartan | 20 mg OD | 40 mg OD | |
| CCB | Amlodipine | 5 mg OD | 10 mg OD |
| Felodipine | 5 mg OD | 10 mg OD | |
| Nifedipine | 5 mg TDS | 20 mg TDS | |
| Diuretic | Hydrochlorothiazide | 12.5 mg OD | 25 mg OD |
| Indapamide SR | 1.5 mg OD | 1.5 mg OD | |
| β-blocker | Bisoprolol | 5 mg OD (CrCl <40: 2.5 mg/day) | 20 mg/day |
| Metoprolol | 50 mg BD | 200 mg BD | |
| Atenolol | 50 mg OD | 100 mg OD | |
| Carvedilol | 12.5 mg OD | 50 mg OD (HF/angina dosing differs) | |
| α-blocker | Doxazosin | 1 mg OD | 16 mg OD |
| Prazosin | 0.5 mg BD-TDS | 20 mg in divided doses |
Diabetes mellitus
HbA1c target
| ≤6.5% (Tight) | 6.6%-7.0% | 7.1%-8.0% (Less tight) |
|---|---|---|
|
|
|
Elderly (Table 6-2): set the target by frailty and life expectancy, not age alone.
| Health status | HbA1c | Fasting glucose (mmol/L) | Pre-bed glucose (mmol/L) | BP |
|---|---|---|---|---|
| Healthy (few illnesses, cognition and function intact) | ≤7.5% | 5.0-7.2 | 5.0-8.3 | <140/90 |
| Complex/intermediate (≥3 chronic illnesses, or mild-moderate cognitive/functional impairment) | <8.0% | 5.0-8.3 | 5.6-10.0 | <140/90 |
| Very complex/poor health (long-term care, end-stage illness, moderate-severe impairment) | <8.5% | 5.6-10.0 | 6.1-11.1 | <150/90 |
Starting treatment by HbA1c
Metformin + lifestyle modification for everyone unless intolerant or contraindicated (½ dose at DKD stage 3B, stop at stages 4-5).
| HbA1c / FPG at diagnosis | Start with |
|---|---|
| <6.5% and FPG <6.0 | Lifestyle; consider metformin monotherapy. If PPG >11.0 or metformin not tolerated: meglitinide, AGI or DPP4-i |
| 6.5-7.4% or FPG 6.0-7.9 | Mono- or dual therapy: metformin, SU, DPP4-i, GLP1-RA or SGLT2-i |
| 7.5-8.4% or FPG 8.0-9.9 | Dual combination |
| 8.5-10.0% or FPG 10.0-13.0 | Triple combination |
| >10.0% or FPG >13.0, or symptomatic hyperglycaemia | Basal/premixed insulin + combination therapy, or intensive insulin + OGLD |
Optimise the dose over the next 3-6 months and repeat HbA1c after 3-6 months. Adding a DPP4-i early may delay loss of glycaemic control.
Choosing by patient profile
After metformin, in order of preference:
| Profile | 2nd | 3rd | 4th | 5th | 6th |
|---|---|---|---|---|---|
| Overweight/obese | Weight loss (lifestyle) | GLP1-RA / SGLT2-i | The other one (GLP1-RA if on SGLT2-i, or vice versa) | DPP4-i (if not on GLP1-RA) | SU, then basal/premixed insulin |
| Normal weight | DPP4-i or SU | SU (if DPP4-i given) | SGLT2-i | GLP1-RA | Basal/premixed insulin |
| High risk of hypoglycaemia | DPP4-i | SGLT2-i | TZD | GLP1-RA | Low-dose 2nd-generation SU, then insulin (analogues) |
| DKD stage 3-5 | SGLT2-i (stop when dialysis starts) | GLP1-RA (contraindicated eGFR <15) | DPP4-i | SU (not advisable stage 4-5) | Basal/premixed insulin |
| High-risk CVD | GLP1-RA | SGLT2-i | DPP4-i (if not on GLP1-RA) or SU | SU (if DPP4-i given) | TZD, then insulin |
| ASCVD | SGLT2-i / GLP1-RA | The other one | DPP4-i (if not on GLP1-RA) or SU | SU (if DPP4-i given) | TZD, then insulin |
| Heart failure | SGLT2-i | GLP1-RA | DPP4-i (if not on GLP1-RA) or SU | SU (if DPP4-i given) | Basal/premixed insulin |
Reaching the HbA1c target is still the priority. If the newer drugs aren't accessible because of cost, use what is proven efficacious and safe.
Glycaemic escalation
Review every 3-6 months. If HbA1c is still above the individualised target on lifestyle + current therapy (after checking adherence):
| HbA1c above target | Do |
|---|---|
| 0.5-1% | Add 1 GLD from a different class, or intensify insulin if already on it |
| 1-2% | Consider 2 GLDs from different classes, or intensify insulin |
| >2% | Start insulin ± GLP1-RA, or intensify insulin |
- Maximum of 5 OGLDs.
- Leave enough time to titrate the current drug before adding the next one.
- Reassess HbA1c after 3-6 months.
- Once on insulin, continue metformin / SGLT2-i / DPP4-i / GLP1-RA. Stop the SU once on full insulin.
Insulin: start and titrate
When to start: on maximal OGLDs and HbA1c >7% or above the individualised target, or at diagnosis with HbA1c >10% / FPG >13 / symptomatic hyperglycaemia.
- Basal insulin 10 U OD or 0.1-0.2 U/kg/day at bedtime. Titrate to the FPG target, +2 U every 3 days (or adjust 2 U weekly based on 3 days of readings).
- Hypoglycaemia → reduce the dose by 10-20%.
- If HbA1c is still above target despite adequate titration, or basal dose is >0.5 U/kg, or FPG is at target: move to basal plus:
- Add prandial insulin 4 U/meal or 10% of the basal dose, one meal at a time.
- Titrate prandial insulin +1-2 U or 10-15% every 3 days.
- Hypoglycaemia → reduce prandial insulin by 10-20%.
- Then basal-bolus.
- If FPG is at target but daytime glucose is high, consider a basal insulin analogue.
Premixed route: premixed/co-formulation OD at the main meal → BD → premixed analogue TDS → basal-bolus.
Glycaemic de-escalation
The CPG supports reducing doses or stopping glucose-lowering drugs when there is:
- Better glycaemic control
- Successful weight loss with lifestyle
- A change in glycaemic goal, especially in the elderly (see the frailty table above)
- A new co-morbidity
- Intolerable side effects
- Treatment that isn't working
| Situation | De-escalate |
|---|---|
| Elderly with multiple co-morbidities, poor life expectancy, organ failure or end of life | De-escalate or stop treatment; relax targets |
| Intensifying insulin | Reduce or stop the SU (stop once on full insulin) |
| Hypoglycaemia on insulin | Basal or prandial dose down by 10-20% |
| Age >60 on glibenclamide | Switch: glibenclamide not recommended >60 years. Gliclazide/glimepiride have less hypo risk |
| eGFR 30-44 on metformin | Halve the dose; stop at <30 |
| eGFR <30 on SGLT2-i | Do not initiate below 30; may continue if already started; stop when dialysis starts |
Glucose-lowering drug doses
| Generic name | Usual dose† | Dose adjustment in renal failure | ||
|---|---|---|---|---|
| Mild (CKD 2) GFR 60-89 | Moderate (CKD 3) GFR 30-59 | Severe (CKD 4 & 5) GFR <30 | ||
| Biguanide | ||||
| Metformin | 500-1000 mg BD | Continue | 45-59: No dose adjustment | Avoid |
| 30-44: 50% dose reduction | ||||
| Sulphonylurea | ||||
| Glibenclamide | 5 mg OD-10 mg BD | Use with caution | Avoid | |
| Gliclazide | 80 mg OD-160 mg BD | No dose adjustment | Caution | |
| Gliclazide MR | 30-120 mg OD | No dose adjustment | Caution | |
| Glimepiride | 1-6 mg OD | Initiate with 1 mg OD | ≥15: Caution<15: Avoid | |
| Glipizide | 2.5 mg OD-10 mg BD | No dose adjustment | Caution | |
| Meglitinides | ||||
| Repaglinide | 0.5-4 mg TDS | No dose adjustment | Initiate at 0.5 mg with meals | |
| Alpha-glucosidase inhibitor | ||||
| Acarbose | 25-100 mg TDS | 50-100% | ≥25: 50-100%<25: Avoid | |
| Thiazolidinediones | ||||
| Pioglitazone | 15-45 mg OD | No dose adjustment (caution with fluid retention risk) | ||
| DPP4-i | ||||
| Sitagliptin | 100 mg OD | No dose adjustment | ≥50: No dose adjustment | 25 mg OD |
| 30-<50: 50 mg OD | ||||
| Vildagliptin | 50 mg OD-BD | No dose adjustment | ≥50: No dose adjustment | |
| <50: 50 mg OD (limited data) | ||||
| Saxagliptin | 2.5-5 mg OD | No dose adjustment | >50: No dose adjustment | |
| ≤50: 2.5 mg OD | ||||
| Linagliptin | 2.5-5 mg OD | No dose adjustment | ||
| GLP1-RAs | ||||
| Exenatide IR | 5 µg/20 µL; 10 µg/40 µL | No dose adjustment | >50: No dose adjustment | Avoid |
| 30-50: Caution in initiating or escalating dose from 5 to 10 mcg | ||||
| Exenatide ER | 2 mg weekly | No dose adjustment | >50: No dose adjustment | Avoid |
| 30-50: Use with caution | ||||
| Liraglutide | 6 mg/mL | No dose adjustment | No dose adjustment | ≥15: No dose adjustment<15: Avoid |
| 3 mg | No dose adjustment | No dose adjustment | Avoid | |
| Lixisenatide | 50 µg/mL; 100 µg/mL | No dose adjustment | No dose adjustment | Avoid |
| Dulaglutide | 0.75-1.5 mg weekly | No dose adjustment | No dose adjustment | ≥15: No dose adjustment<15: Avoid |
| Semaglutide | 0.5-1.0 mg weekly | No dose adjustment | No dose adjustment | ≥15: No dose adjustment<15: Avoid |
| SGLT2 inhibitors* | ||||
| Dapagliflozin | 5-10 mg OD | No dose adjustment | 45-59: No dose adjustment | Avoid |
| 30-44: Not recommended | ||||
| Canagliflozin | 100-300 mg OD | No dose adjustment | 45-59: 100 mg OD | Avoid |
| 30-44: Not recommended | ||||
| Empagliflozin | 10-25 mg OD | No dose adjustment | No dose adjustment | Avoid |
| Ertugliflozin | 5-15 mg OD | No dose adjustment | 45-59: No initiation | Avoid |
| 30-44: Not recommended | ||||
| Luseogliflozin | 2.5-5 mg OD | No dose adjustment | <60: Not recommended | Avoid |
| Insulin | ||||
| Doses should be adjusted based on frequent monitoring to balance goals of glycaemic control with avoiding hypoglycaemia. Long-acting tends to accumulate longer than short-acting insulin. | ||||
Adapted from Appendix 7, CPG T2DM 2020. †Usual dose, not maximum dose; dose escalation depends on tolerability and the product insert. GFR in mL/min/1.73 m².
*These SGLT2-i cut-offs are for glucose lowering. For kidney protection, the CPG's DKD section says SGLT2-i slow DKD progression down to eGFR 25-30. Don't initiate below 30, but you may continue if already started. Stop at dialysis.
GLP1-RA doses
| Drug | Start | Usual dose | Renal |
|---|---|---|---|
| Liraglutide | 0.6 mg OD for ≥1 week | 1.2-1.8 mg OD | eGFR <15 avoid |
| Dulaglutide | No titration | 0.75 mg weekly (mono), 1.5 mg weekly (add-on) | eGFR <15 avoid |
| Semaglutide | 0.25 mg weekly for 4 weeks | 0.5-1.0 mg weekly (increase after 4 weeks if needed) | eGFR <15 avoid |
| Exenatide | 5 µg BD for ≥1 month | 5-10 µg BD, within 60 min before main meals | eGFR <30 avoid |
| Exenatide ER | No titration | 2 mg weekly | eGFR <30 avoid |
| Lixisenatide | 10 µg OD for 14 days | 20 µg OD | eGFR <30 avoid |
Dyslipidaemia
LDL-C target
| Risk category | Who | LDL-C (mmol/L) | Non-HDL-C (mmol/L) |
|---|---|---|---|
| Very high | Diabetes + established CVD, or other target organ damage, or ≥3 risk factors | <1.4 | <2.2 |
| High | Diabetes ≥10 years, no target organ damage, plus any other risk factor | <1.8 | <2.6 |
| Moderate | Age <50, T2DM <10 years, no other risk factors | <2.6 | <3.4 |
- Every T2DM patient over 40 gets a statin, whatever the baseline LDL-C. Below 21 years without ASCVD, a statin is generally not recommended.
- If the target is not achievable, aim for a ≥50% reduction from the pre-treatment LDL-C.
- Non-HDL-C = total cholesterol - HDL-C (target = LDL-C target + 0.8). Use it when TG >4.5 mmol/L and LDL-C can't be calculated.
- A non-fasting sample is fine for a lipid profile. Repeat fasting only if non-fasting TG >2.3 mmol/L.
Choosing lipid drugs
| Goal | First drug | Add, in order |
|---|---|---|
| Lower LDL-C | Statin | Ezetimibe → PCSK9 inhibitor → BAS (may raise TG) |
| Lower TG | Fibrate | Omega-3 → statin (high dose may be needed) → nicotinic acid |
| Combined hyperlipidaemia | Statin | Fibrate → BAS + fibrate → PCSK9 → ezetimibe |
Lipid escalation
Statin → intensify to the maximum tolerated dose → + ezetimibe → + PCSK9 inhibitor (very high risk).
Other lipid problems:
- TG >5.7 mmol/L (fasting): look for secondary causes and consider a fibrate and/or fish oil (2-4 g/day) to reduce pancreatitis risk.
- TG >10 mmol/L with high pancreatitis risk that doesn't respond to fibrate/fish oil: nicotinic acid.
- TG >2.3 with low HDL-C: fibrate + statin may be considered.
- Established retinopathy: fenofibrate slows progression, whatever the TG/HDL.
Lipid de-escalation
The CPG has no step-down plan for statins. What it says:
- Statins are long-term: in the healthy elderly, continue "as long as tolerated" (Table 6-2).
- Very complex/poor health elderly (long-term care, end-stage illness): individualise. Weigh the likely benefit of the statin, which is greatest for secondary prevention.
- Pregnancy: statins are contraindicated. Don't use them in women of child-bearing potential without adequate contraception.
Statin doses by intensity
| High intensity | Moderate intensity | Low intensity | |
|---|---|---|---|
| LDL-C lowering | ≥50% | 30-49% | <30% |
| Statins | Atorvastatin 40-80 mg | Atorvastatin 10-20 mg | |
| Rosuvastatin 20-40 mg | Rosuvastatin 5-10 mg | ||
| Simvastatin 20-40 mg | Simvastatin 10 mg | ||
| Pravastatin 40-80 mg Lovastatin 40-80 mg | Pravastatin 10-20 mg Lovastatin 20 mg |
Adapted from Table 3-30, CPG T2DM 2020.
Expected LDL-C reduction: statin 30-60%, ezetimibe 10-20%, PCSK9 inhibitor ~60%.
Sources
- Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Type 2 Diabetes Mellitus, 6th Edition. 2020. Tables 3-5, 3-6, 3-25 to 3-30, 6-2; Figures 3-4 and the treatment algorithms; Appendix 7. MOH CPG - Endocrine
- Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Hypertension, 5th Edition. 2018. Section 5.4 (step-down) and Tables 9.1-A to 9.5-B (dosing, referenced from MIMS 2018). MaHTAS