Nota Medik
Type 2 Diabetes: HbA1c Targets, Drug Choice, Escalation, De-escalation & Doses
Contents
Type 2 diabetes in one place: HbA1c targets, which drug to start and add, how to escalate (including insulin) and de-escalate, and the usual doses with renal adjustment. Based on the CPG Management of T2DM (6th Edition, 2020).
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 HbA1c target) | |
| 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 BP and lipids in diabetes) | |
| 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 | |
Remark: HbA1c = glycated haemoglobin; HDL-C / LDL-C = high- / low-density lipoprotein cholesterol. Adapted from Table 3-5, CPG T2DM 2020. Table 3-27 gives the female HDL-C target as >1.3 mmol/L.
HbA1c target
| ≤6.5% (Tight) | 6.6%-7.0% | 7.1%-8.0% (Less tight) |
|---|---|---|
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|
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Remark: CVD = cardiovascular disease; CAD = coronary artery disease; eGFR = estimated glomerular filtration rate (mL/min/1.73 m²); CLD = chronic liver disease. Adapted from Table 3-6, CPG T2DM 2020.
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 |
Remark: FPG = fasting plasma glucose (mmol/L); PPG = post-prandial glucose; AGI = alpha-glucosidase inhibitor; SU = sulphonylurea; DPP4-i = dipeptidyl peptidase-4 inhibitor; GLP1-RA = GLP-1 receptor agonist; SGLT2-i = SGLT2 inhibitor; OGLD = oral glucose-lowering drug.
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 |
Remark: SGLT2-i = sodium-glucose cotransporter-2 inhibitor; GLP1-RA = glucagon-like peptide-1 receptor agonist; DPP4-i = dipeptidyl peptidase-4 inhibitor; SU = sulphonylurea; TZD = thiazolidinedione (pioglitazone); DKD = diabetic kidney disease; CVD = cardiovascular disease; ASCVD = atherosclerotic cardiovascular disease.
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 |
Remark: GLD = glucose-lowering drug; GLP1-RA = GLP-1 receptor agonist.
- 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.
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 |
Remark: SU = sulphonylurea; SGLT2-i = SGLT2 inhibitor; eGFR in mL/min/1.73 m².
Usual doses
Glucose-lowering drugs (renal adjustment)
| 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. | ||||
Remark: CKD = chronic kidney disease; GFR = glomerular filtration rate; OD / BD / TDS = once / twice / three times daily; MR = modified release; IR / ER = immediate / extended release; DPP4-i, GLP1-RA, SGLT2 = as above. 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
| 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 |
Remark: OD = once daily; BD = twice daily; ER = extended release; eGFR in mL/min/1.73 m².
BP and lipids in diabetes
BP
- Start drugs when BP is persistently ≥140 systolic and/or ≥90 diastolic.
- Target SBP 130-139 mmHg, DBP 70-79 mmHg; SBP <130 (not <120) if no pre-existing CHD and at higher risk of stroke or DKD; DBP not <70.
- ACEi or ARB first line, titrated to the maximum recommended dose; most need 3 drugs (add a CCB or diuretic). Never ACEi + ARB.
Full details, drug choice and doses: Hypertension.
Lipids
- Every person with diabetes over 40 gets a statin, whatever the baseline LDL-C. Below 21 years without clinical CVD, a statin is generally not recommended.
- The LDL-C target depends on CV risk (T2DM CPG 2020, Table 3-26):
| 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 |
Remark: CVD = cardiovascular disease; non-HDL-C = total cholesterol - HDL-C. The newer Dyslipidaemia CPG 2023 puts it as ≤1.4 mmol/L and a >50% reduction (very high risk), ≤1.8 mmol/L and a >50% reduction (high risk), <2.6 mmol/L (diabetes <50 years, <10 years' duration, no other risk factors).
- Statin first; intensify to the maximum tolerated dose, then add ezetimibe, then a PCSK9 inhibitor (very high risk).
Full details, statin intensities and doses: Dyslipidaemia.
Sources
- Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Type 2 Diabetes Mellitus, 6th Edition. 2020. Tables 3-5, 3-6, 3-16, 3-25, 3-26, 6-2; Figure 3-4 and the treatment algorithms; Appendix 7. MOH CPG - Endocrine
- National Heart Association of Malaysia, Ministry of Health Malaysia, Academy of Medicine of Malaysia. Clinical Practice Guidelines: Management of Dyslipidaemia, 6th Edition. 2023. Table 4. MOH