Achieving control in type 2 diabetes (Guidelines)

SELF-MANAGEMENT:

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.

FIRST LINE:

Oral monotherapy

METFORMIN (MET)

• (SUs, SGLT2 inhibitors (flozins), DPP4 inhibitors (gliptins) or pioglitazone can all be used as alternate first line therapies in metformin intolerance)

SECOND LINE:

Oral dual therapy

SU + MET

MET + ONE of the following:

• DPP-4 inhibitors (gliptins): Consider if weight gain and / or hypos are a concern.
• SU: Consider if BMI <27kg/m² but can be used at any BMI.
• PIOGLITAZONE (PIO): Consider if hypos are a concern. See: Pioglitazone prescribing algorithm (Guidelines). Avoid in heart failure.
• SGLT2 inhibitors (flozins): Consider if weight gain and/or hypos are a concern and/or high CV risk or heart failure.
  Do not initiate for glucose lowering alone if eGFR<60.

THIRD LINE:

Oral triple therapy

Not appropriate.

Requires insulin initiation.

MET + TWO of the following: 

• DPP-4 inhibitors: Consider if weight gain and/or hypos are a concern.
• SU: Consider if BMI <27kg/m² but can be used at any BMI. 
• PIO: Consider if hypos are a concern. See: Pioglitazone prescribing algorithm (Guidelines). Avoid in heart failure.
• SGLT2 inhibitors: Choose if weight gain and/or hypos are a concern and/or high CV risk or heart failure.
  Do not initiate for glucose lowering alone, if eGFR<60.

OR consider INJECTABLE THERAPY, eg:

• Insulin: if BMI <30kg/m²
• GLP-1 RA or dual GIP/GLP-1 RA: if BMI >30kg/m² and high CV risk.

Alternative THIRD LINE:

if high CV risk or obesity

Not appropriate.

Requires insulin initiation.

GLP-1 RA or dual GIP/GLP-1 RA: can be used with insulin, metformin and/or SGLT2 inhibitor:

• Stop DPP-4 and consider reduction of SU / insulin dose on initiation.
• Injectable GLP-1 preferred (if available) given proven CV benefit.

INSULIN therapies

Usually start with basal insulin at bed:

• Use NPH / isophane insulin: eg Humulin I.
• Analogue insulin: eg Insulin glargine, can be considered if high risk of hypoglycaemia or once daily administration by district nurse.
• Can continue metformin and/or SGLT2 inhibitor.
• Caution if on PIO (risk of fluid retention).
• Consider reducing or stopping SU.

Notes: 

• Hypos concern: Falls in the elderly, driving, occupation, alcohol consumption.
• Favour SGLT2 inhibitors / GLP-1 receptor agonists in individuals with cardiovascular and renal disease. 

Initiation dose

40 to 80mg before breakfast

2·5 to 5mg before breakfast

500mg with breakfast for 1 week, then 500mg twice daily.

Dose titration increment

40 to 80mg

2·5 to 5mg

500mg to 1 gram

Titration interval

• 3 monthly
• If using SMBG <3 monthly

3 monthly

Maximum dose

160mg twice daily before meals

20mg daily, as divided doses, with meals

1 gram twice daily

Treatment failure criteria

<5·5mmol/mol reduction in HbA1c in 6 months

• Unless at individualised target.
• If treatment failure criteria not met on maximum tolerated dose consider withdrawal of medication, substitution or addition of another medication.

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

Hepatic impairment

Reduce dose

Withdraw, if tissue hypoxia likely

Notes

• Weight gain
• SMBG at higher doses

• Low risk of hypo
• Stop during any dehydrating illness or if acutely unwell
• Consider modified release preparation in those with GI side effects

Initiation dose

• 15mg once daily if elderly or on insulin
• 30mg once daily for all other patients

25mg once daily

5mg once daily

Dose titration increment

15mg

N/A

Titration interval

• Elderly or on insulin: 3 months if no ADRs
• Other patients: 6 months

N/A

Maximum dose

45mg daily

25mg daily

5mg daily

Treatment failure criteria

<5·5mmol/mol reduction in HbA1c in 6 months

• Unless at individualised target.
• If treatment failure criteria not met on maximum tolerated dose, consider withdrawal of medication, substitution or addition of another medication.

Renal impairment

≥30 to <50mL/min:
12.5mg once daily

<30mL/min: 6.25mg once daily

Hepatic impairment

Notes

• Avoid in any degree of LV dysfunction
• Weight gain
• 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

Initiation dose

10mg once daily

If severe hepatic impairment: 5mg once daily

100mg once daily

10mg once daily

Not recommended if >85 years

Dose titration increment

N/A

To 300mg daily

Can be increased to 25mg once daily

Titration interval

N/A

If no side effects at 3 to 6 months

Maximum dose

10mg daily

300mg

Reduce to 100mg/day if eGFR falls <60mL/min

25mg daily

Reduce to 10mg if eGFR falls <60mL/min

Treatment failure criteria

<5·5mmol/mol reduction in HbA1c in 6 months, unless using for renoprotection or heart failure

<5·5mmol/mol reduction in HbA1c in 6 months, unless using for CV benefit or heart failure

• Unless at individualised target.
• If treatment failure criteria not met on maximum tolerated dose, consider withdrawal of medication, substitution or addition of another medication.

Renal impairment

Can continue if eGFR <45mL/min for renoprotection or heart failure

Can continue if eGFR <45 mL/min for renoprotection if proteinuria

Can continue if eGFR <45mL/min for CV benefits or heart failure

Hepatic impairment

5mg daily, increase according to response

Avoid in severe hepatic impairment

Notes

See additional guidance on prescribing for renal / cardiac disease

• Promotes weight loss
• Low risk of hypo
• Risk of DKA
• Discontinue if acutely unwell or dehydrating illness
• For canagliflozin: Avoid if high risk feet

Initiation dose

0.25mg once weekly

Prescribe single prefilled 0.25mg pen

3mg once daily

Take on empty stomach 30mins before eating / drinking / other meds

1.5mg once weekly

0.75mg weekly if monotherapy

2.5mg once weekly

Dose titration increment

Increase to 0.5mg after 4 weeks (using 0.5mg pen)

To 7mg, then 14mg

1.5mg

2.5mg

Titration interval

4 weeks

6 months, if required

Monthly, continue at lowest effective dose

Maximum dose

1mg* once weekly

14mg daily

4·5mg once weekly

15mg once weekly

Treatment failure criteria

<11mmol/mol of reduction in HbA1c ±<3% weight loss in 6 months

Weight loss <5% and/or HbA1c reduction <5mmol/mol at 6 months

• Unless at individualised target.
• If treatment failure criteria not met on maximum tolerated dose, consider withdrawal of medication, substitution or addition of another medication.

Renal impairment

Avoid if eGFR <15mL/min

No dose adjustment required

Hepatic impairment

Avoid in severe hepatic impairment

No dosage adjustment required

Use with caution in severe hepatic impairment

Notes

Caution if diabetic retinopathy

NB: needle pre-attached

Caution if diabetic retinopathy

Low risk of hypo (reduce /stop SU)

May reduce effectiveness of oral contraceptive pill

• Promotes weight loss
• Avoid if history of pancreatitis
• Diabetes <10yrs
• For full prescribing details, including all cautions. contra-indications, adverse effects, see BNF.

Initiation dose

600 micrograms once daily

2mg once weekly

Dose titration increment

600 micrograms once daily

N/A

Titration interval

Increase from 0.6mg at 1 week

N/A

Maximum dose

Usually 1·2mg once daily

Exceptionally 1·8mg/day

2mg once weekly

Treatment failure criteria

<11mmol/mol of reduction in HbA1c ±<3% weight loss in 6 months

• Unless at individualised target.
• If treatment failure criteria not met on maximum tolerated dose, consider withdrawal of medication, substitution or addition of another medication.

Renal impairment

Avoid if eGFR <30mL/min

Avoid if eGFR <30mL/min

Hepatic impairment

Avoid in severe hepatic impairment

Dose as in normal hepatic function

Notes

• Promotes weight loss
• Avoid if history of pancreatitis
• Diabetes <10yrs
• For full prescribing details, including all cautions. contra-indications, adverse effects, see BNF.