Achieving control in type 2 diabetes (Guidelines)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

Audience

  • North NHS Highland only
  • Primary and Secondary Care
  • Adults only

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

Discontinue new agents if no evidence of effectiveness (ie <5.5mmol/mol improvement in HbA1c) at 3 to 6 months.

HbA1c target individualised eg: 

  • ≤53mmol/mol on single agent
  • ≤58mmol/mol on two or more agents.

Place of therapy

  Patient <25kg/m2
    OR
Osmotic symptoms
if weight loss, check ketones
?T1DM		 Patient ≥25kg/m2

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

 SULFONYLUREA (SU)

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. 

Sulphonylureas and metformin

Prescribing information

Medication

SU: Gliclazide

SU: Glipizide

Biguanide: Metformin
(standard preparation)

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
For full prescribing information, including all cautions, contra-indications and adverse effects, see BNF.

Thiazolidinedione and DPP4 inhibitors

Pioglitazone prescribing algorithm

Treatment failure criteria: <5·5mmol/mol reduction in HbA1c in 6 months.

  • Unless at individualised target.
  • If treatment failure criteria met on maximum tolerated dose: consider withdrawal of medication, substitution or addition of another medication.

Prescribing information

Medication

Thiazolidinedione: Pioglitazone

DPP4-I: Alogliptin

DPP4-I: Linagliptin

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

 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

 Avoid Avoid in severe hepatic impairment Dose as in normal hepatic function

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
For full prescribing information, including all cautions, contra-indications, adverse effects, see BNF. 

SGLT2 inhibitors

SGLT2 inhibitors are a relatively new class of drug initially licensed for their glucose lowering effects in type 2 diabetes.

Evidence suggests they provide benefits beyond HbA1c reduction, eg, reducing risk of hospitalisation for heart failure, cardiovascular death, and progression of diabetic nephropathy. 

Factors to consider when prescribing SGLT2 inhibitors in T2DM

Some agents have licenses for specific indications. The following flow chart demonstrates some of the factors to consider when considering initiation of an SGLT2 inhibitor.

Prescribing information 

Sodium-glucose co-transporter 2 (SGLT2) inhibitors (Formulary)

Further details regarding prescribing in renal / hepatic impairment can be found in the table below.

Consideration should also be given to reducing sulfonylurea or insulin dose, if adding in an SGLT2 inhibitor, to reduce risk of hypoglycaemia.

Importantly, glucose lowering effects are dependent on adequate renal function.

  • Hence SGLT2 inhibitors should NOT be started for glucose lowering if eGFR <60mL/min.
  • However, they can be commenced with an eGFR between 30 to 60mL/min for renoprotection in individuals with proteinuria or in the management of heart failure with reduced ejection fraction, along with ACE inhibitor/ARB etc.
    If used for these specific indications then they should be continued if eGFR drops <45mL/min, unless in the context of acute kidney injury, and can be continued if eGFR drops <30mL/min.

Medication

Dapagliflozin

Canagliflozin

Empagliflozin

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
For full prescribing information, including all cautions, contra-indications and adverse effects, see BNF.

GLP-1 RA & dual GIP/GLP-1 RA

Indication

  • For use in individuals with type 2 diabetes and a BMI 30kg/m2 or over
  • Third-line agent where as a combination therapy HbA1c is above target of 58mmol/mol
  • Fourth-line agent as a combination therapy with oral antihyperglycaemics and insulin
If patient on insulin, can be considered with lower HbA1c if may benefit from insulin reduction.
If adding to existing therapy of a sulfonylurea or insulin, consider a lower dose of sulfonylurea / insulin to reduce the risk of hypoglycaemia.

Prescribing details

GLP-1 RA & dual GIP/GLP-1 RA (Formulary)

  • FIRST LINE:  Semaglutide. Increased clinical effectiveness. 
    • Once weekly, injectable
    • Once daily, oral tablets. Alternative when subcutaneous route not suitable.
  • SECOND LINE: Dulaglutide
    • Once weekly, injectable. Needle is hidden, may be suitable in needle phobia. 
  • THIRD LINE: Tirzepatide
    • Once weekly, injectable. Less cost-effective option.

Medication

Semaglutide Sub-cut (Weekly)

Semaglutide Oral (Daily)

Dulaglutide Sub-cut  (Weekly)

Tirzepatide Sub-cut
(weekly)

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.

*Licensed max is 2mg, however the recommended maximum dose for diabetes is 1mg, and this is the highest available dose in the UK.

Non-formulary medication, for existing patients still taking these medicines. 

Medication

Liraglutide Sub-cut (Daily)

Non-formulary

Exenatide Sub-cut (Weekly)

Discontinued

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.

Clinical review

Review effect of therapy after 6 months. 
Expected beneficial effects:
  • HbA1c:   
    • Reduction of 11mmol/mol (1%)
    • OR treatment target of <59mmol/mol met
  • Weight: Reduction of 3% of initial weight

Further review

  • Consider other factors that may preclude the use of insulin. For example: occupation, social situation and ability to cope with insulin.

Abbreviations

  • DPP-4: Dipeptidylpeptidase-4 inhibitor
  • GIP/GLP-1 RA: Glucose-dependent insulinotropic polypeptide/Glucagon-like peptide-1 receptor agonist
  • GLP-1 RA: Glucagon-like peptide-1 receptor agonist
  • MET: Metformin
  • PIO: Pioglitazone
  • SGLT2: Sodium-glucose co-transporter 2 inhibitor
  • SMBG: Self-monitoring of blood glucose
  • SU: Sulfonylurea

Editorial Information

Last reviewed: 26/06/2025

Next review date: 30/06/2028

Author(s): Endocrinology (Diabetes Review Group).

Version: 6

Approved By: TAM Subgroup of the ADTC

Reviewer name(s): Dr D MacFarlane, Consultant Endocrinologist..

Document Id: TAM148

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