Achieving Control in Type 2 Diabetes

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Review diet, exercise and adherence to medication before making dose adjustments or prescribing additional therapy

HbA1c target individualised as agreed eg ≤58mmol/mol

Patient factors

<25kg/m
OR 
Weight loss/ osmotic symptoms of hyperglycaemia

>25kg/m2

Diet and exercise

1 month

(Treat immediately if symptomatic)

3 months

First-line oral therapy
(monotherapy)

SULFONYLUREA (SU)

METFORMIN (MET)

Second-line oral therapy
(dual therapy)

SU + MET

MET + ONE of the following:

DPP-4 
Choose if BMI >30kg/m2 and hypos are a concern.*

SU 
Choose if BMI <30kg/m2

PIO 
Choose if BMI <30kg/m2 and hypos are a concern.* See PIO prescribing algorithm.

SGLT2 
Choose if BMI >30kg/m2 and hypos are a concern*.

Note, do not initiate if eGFR<60mL/min.

Third-line oral therapy
(triple therapy)

Not appropriate – require INS initiation

MET + TWO of the following: 
(avoid combining PIO and dapagliflozin)

DPP-4 
Choose if BMI >30kg/m2 and hypos are a concern.*

 

SU 
Choose if BMI <30kg/m2

PIO 
Choose if BMI <30kg/m2 and hypos are a concern.* See PIO prescribing algorithm.

SGLT2 
Choose if BMI >30kg/m2 and hypos are a concern.*

 

GLP-1 therapy

Not appropriate

Licensed combinations include:

  • Dual therapy - GLP-1 + [MET or SU or PIO (not with liraglutide)]
  • Triple therapy - [GLP-1 + MET + SU] or [GLP-1 + MET + PIO]
  • GLP1 may also be used with INS (see below)
    • stop DPP-4
    • consider reduction of SU dose on initiation
    • refer to GLP-1 protocol for further information.

Insulin therapies

 

Insulin monotherapy or licensed combinations include:

  • INS + MET + SU + SGLT2
  • INS + MET + PIO + Exenatide standard preparation or Dulaglutide.
  • INS + Liraglutide or Dulaglutide
    • specialist input required with all INS treatments
    • refer to patient pathways for insulin therapy guidance
  • note increased risk of oedema with PIO + INS.

 

* Falls in the elderly, driving, occupation, alcohol consumption.

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.

 

Medication

Gliclazide

Glipizide

Metformin
(std prep)

Pioglitazone

Linagliptin

Sitagliptin

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 PIO prescribing algorithm)

5mg once daily

100mg 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

5mg daily

100mg 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

Dose as in normal renal function

>30 -<50mL/min 50mg once daily<30mL/min -25mg once daily

Hepatic impairment

Reduce dose

Reduce dose

Withdraw if tissue hypoxia likely

Avoid

Dose as in normal hepatic function

Use with caution in severe hepatic impairment

Notes

Weight gain
SMBG at higher doses

Weight gain
SMBG at higher doses

Low risk of hypo 
Stop metformin during vomiting or diarrhoeal illnesses

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

Weight neutral
Low risk of hypo

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

 

Medication

Dapagliflozin

Empagliflozin

Exenatide (daily)

Exenatide (weekly)

Liraglutide

Dulaglutide

Initiation dose

10mg once daily
(5mg if severe hepatic impairment)
(only initiate if eGFR >60mL/min)
Not recommended if >75 years

10mg once daily (only initiate if eGFR 60mL/min)
Not recommended if >85 years

5 micrograms twice daily
(refer to GLP-1 analogues guidance on p179)

2mg once weekly
(refer to GLP-1 analogues guidance)

600 micrograms once daily
(refer to GLP-1 analogues guidance)

750 micrograms once weekly
(refer to GLP-1 analogues guidance)

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 <45mL/min

If CrCl falls to 45-60mL/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

Promotes weight loss
Low risk of hypo

Promotes weight loss
Diabetes <10yrs
BMI >30kg/m2

Promotes weight loss
Diabetes <10yrs
BMI >30kg/m2
Effect may continue up to 10 weeks after discontinuation

Promotes weight loss
Diabetes <10yrs
BMI >30kg/m2

Promotes weight loss
Diabetes <10yrs
BMI >30kg/m2
Effect may continue for at least 3 weeks after discontinuation

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