Review diet, exercise and adherence to medication before making dose adjustments or prescribing additional therapy and discontinue new agents if no evidence of effectiveness at 3 to 6 months ie <5.5mmol/mol improvement in HbA1c HbA1c target individualised as agreed ≤53mmol/mol on single agent, ≤58mmol/mol on two or more agents |
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Patient factors |
<25kg/m2 |
>25kg/m2 |
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Diet and exercise |
1 month (Treat immediately if symptomatic) |
3 months If appropriate, consider advising patients that remission of type 2 diabetes can be achieved with weight loss of 10 to 15kg |
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First-line oral therapy |
SULFONYLUREA (SU) |
METFORMIN (MET) (SUs, SGLT2 inhibitors ("flozins"). DPP4 inhibitors ("gliptins") or PIO can all be used as alternate first line therapies in metformin intolerance) |
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Second-line oral therapy |
SU + MET |
MET + ONE of the following: |
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DPP-4 inhibitors ("gliptins") |
SU |
PIOGLITAZONE (PIO) |
SGLT2 inhibitors** ("flozins") Note, do not initiate if eGFR<60mL/min. |
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Third-line oral therapy |
Not appropriate – require INS initiation |
MET + TWO of the following: or consider injectable therapy eg insulin in BMI <30kg/m2, GLP1 therapy** if BMI >30kg/m2 |
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DPP-4 inhibitors ("gliptins")
|
SU |
PIO |
SGLT2 inhibitors** ("flozins") |
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GLP-1 therapy |
Not appropriate |
GLP1 may also be used with insulin:
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Insulin therapies |
|
Usually start with basal insulin at bed
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* Falls in the elderly, driving, occupation, alcohol consumption. ** Favour SGLT2 inhibitors and GLP1 receptor agonists in individuals with known cardiovascular disease. |
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SU – sulfonylurea; MET – metformin; PIO – pioglitazone; SGLT2 – sodium-glucose co-transporter 2 inhibitor; DPP-4 – Dipeptidylpeptidase-4 inhibitor; GLP-1 – Glucagon-like peptide-1 analogue; INS – insulin; SMBG – self-monitoring of blood glucose. |
<>Dose as in normal hepatic function
Sulfonylureas | Sulfonylureas | Biguanide | Thiazolidinedione |
DPP4 inhibitors |
DPP4 inhibitors |
|
Medication | Gliclazide | Glipizide | Metformin (std prep) |
Pioglitazone | Alogliptin | Linagliptin |
Initiation dose | 40 to 80mg before breakfast | 2·5 to 5mg before breakfast | 500mg with breakfast for 1 week then 500mg twice daily | 15mg once daily if elderly or on concomitant insulin 30mg once daily for all other patients (refer to P180) |
25mg once daily | 5mg once daily |
Dose titration increment | 40 to 80mg | 2·5 to 5mg | 500mg to 1 gram | 15mg | NA | NA |
Titration interval | 3 monthly (if using SMBG <3 monthly) |
3 monthly (if using SMBG <3 monthly) |
3 monthly | Elderly or on insulin – @3 months if no ADRs Other patients - @6 months |
NA | NA |
Maximum dose | 160mg twice daily before meals | 20mg daily as divided doses with meals | 1 gram twice daily | 45mg daily | 25mg daily | 5mg daily |
Treatment failure critiera# | <5·5mmol/mol reduction in HbA1c in 6 months | <5·5mmol/mol reduction in HbA1c in 6 months | <5·5mmol/mol reduction in HbA1c in 6 months | <5·5mmol/mol reduction in HbA1c in 6 months | <5·5mmol/mol reduction in HbA1c in 6 months | <5·5mmol/mol reduction in HbA1c in 6 months |
Renal impairment |
<50mL/min initially 20 to 40mg daily, monitor closely and use with caution |
<50mL/min initially 2·5mg daily, monitor closely and use with caution |
Avoid if <30mL/min Caution if 30 to 45mL/min |
Dose as in normal renal function |
>30 to <50mL/min 12·5mg once daily <30mL/min - 6·25mg once daily |
Dose as in normal renal function |
Hepatic impairment | Reduce dose | Reduce dose | Withdraw if tissue hypoxia likely | Avoid | Avoid in severe hepatic impairment | |
Notes |
weight gain SMBG at higher doses |
weight gain SMBG at higher doses |
low risk of hypo stop during any dehydrating illness or if acutely unwell |
weight gain avoid in any degree of LV dysfunction takes 4 to 5 months to alter HbA1c small increased risk of bladder Ca consider fracture risk |
weight neutral low risk of hypo avoid in moderate to severe heart failure avoid if history of pancreatitis |
weight neutral low risk of hypo avoid if history of pancreatitis |
#Unless at individualised target. If treatment failure criteria not met on maximum tolerated dose consider withdrawal of medication, substitution or addition of another medication.
SGLT2 inhibitors |
SGLT2 inhibitors |
GLP1 receptor agonists |
GLP1 receptor agonists |
GLP1 receptor agonists |
GLP1 receptor agonists |
|
Medication | Dapagliflozin | Empagliflozin | Exenatide (daily) | Exenatide (weekly) | Liraglutide | Dulaglutide |
Initiation dose |
10mg once daily |
10mg once daily (only initiate if CrCl ≥60mL/min) Not recommended if >85 years |
5 micrograms twice daily (refer to GLP-1 analogues guidance on p181) |
2mg once weekly (refer to GLP-1 analogues guidance on p181) |
600 micrograms once daily (refer to GLP-1 analogues guidance on p181) |
750 micrograms once weekly (refer to GLP-1 analogues guidance on p181) |
Dose titration increment | NA | Increase to 25mg once daily | 5 micrograms twice daily | NA | 600 micrograms once daily | If add-on therapy, 750 micrograms once weekly |
Titration interval | NA |
If no side-effects |
1 month at initiation dose then titrate if no side-effects |
NA |
1 to 2 weeks at initiation dose then titrate if no side-effects |
If no side-effects |
Maximum dose | 10mg daily | 25mg daily |
10 micrograms twice daily |
2mg once weekly | Usually 1·2mg once daily, exceptionally 1·8mg once daily |
1·5mg once weekly |
Treatment failure criteria# | <5·5mmol/mol reduction in HbA1c in 6 months | <5·5mmol/mol reduction in HbA1c in 6 months | <11mmol/mol reduction in HbA1c + <3% reduction in weight in 6 months | <11mmol/mol reduction in HbA1c +<3% reduction in weight in 6 months | <11mmol/mol reduction in HbA1c + <3% reduction in weight in 6 months | <11mmol/mol reduction in HbA1c +<3% reduction in weight in 6 months |
Renal impairment | Avoid if eGFR <60mL/min. Discontinue if eGFR <45mL/min | If CrCl falls to 45 to 60mL/min, 10mg daily. Avoid if <45mL/min | Avoid if <30mL/min Caution if 30 to 50mL/min |
Avoid if <50mL/min. Dose as normal if >50mL/min |
Avoid if <30mL/min | Avoid if <30mL/min |
Hepatic impairment | 5mg daily, increase according to response | Avoid in severe hepatic impairment | Dose as in normal hepatic function | Dose as in normal hepatic function | Avoid | No dosage adjustment required in patients with hepatic impairment |
Notes |
promotes weight loss Low risk of hypo risk of DKA discontinue in any dehydrating illness or if acutely unwell |
promotes weight loss low risk of hypo risk of DKA discontinue in any dehydrating illness or if acutely unwell |
promotes weight loss diabetes <10yrs BMI >30kg/m2 avoid if history of pancreatitis |
promotes weight loss diabetes <10yrs BMI >30kg/m2 effect may continue up to 10 weeks after discontinuation avoid if history of pancreatitis |
promotes weight loss diabetes <10yrs BMI >30kg/m2 avoid if history of pancreatitis |
promotes weight loss diabetes <10yrs BMI >30kg/m2 effect may continue for at least 3 weeks after discontinuation avoid if history of pancreatitis |
#Unless at individualised target. If treatment failure criteria not met on maximum tolerated dose consider withdrawal of medication, substitution or addition of another medication.