Achieving control in type 2 diabetes (guidelines)

TAM (Treatments and Medicines) NHS Highland

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July 2024: Previous pdf table transposed to TAM template.

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

Prescribing details: Sulphonylureas and metformin

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

Prescribing details: Thiazolidinedione and DPP4 inhibitors

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

Prescribing details: SGLT2 inhibitors

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
Treatment failure criteria	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

Prescribing details: GLP-1 RA & dual GIP/GLP-1 RA

Medication	Liraglutide (Daily)	Semaglutide (Weekly)	Dulaglutide (Weekly)	Exenatide (Weekly)	Semaglutide (Daily)	Tirzepatide (weekly)
	GLP-1 RA (subcut)				GLP-1 RA (Oral)	GIP/GLP-1 RA (subcut)
Initiation dose	600 micrograms once daily	0.25mg once weekly Prescribe single prefilled 0.25mg pen	1.5mg once weekly 0.75mg weekly if monotherapy	2mg once weekly	3mg once daily Take on empty stomach 30mins before eating / drinking / other meds	2.5mg once weekly
Dose titration increment	600 micrograms once daily	Increase to 0.5mg after 4 weeks (using 0.5mg pen)	1.5mg	N/A	To 7mg, then 14mg	2.5mg
Titration interval	Increase from 0.6mg at 1 week	4 weeks	6 months, if required	N/A	4 weeks	Monthly, continue at lowest effective dose
Maximum dose	Usually 1·2mg once daily Exceptionally 1·8mg/day	1mg once weekly	4·5mg once weekly	2mg once weekly	14mg daily	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
Treatment failure criteria	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 <15mL/min	Avoid if eGFR <15mL/min	Avoid if eGFR <30mL/min	Avoid if eGFR <15mL/min	No dose adjustment required
Hepatic impairment	Avoid in severe hepatic impairment	Avoid in severe hepatic impairment	No dosage adjustment required	Dose as in normal hepatic function	Avoid in severe hepatic impairment	Use with caution in severe hepatic impairment
Notes	Promotes weight loss Avoid if history of pancreatitis Diabetes <10yrs
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

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

Last reviewed: 17/02/2022

Next review date: 30/06/2027

Author(s): Diabetes Review Group.

Version: 5.1

Approved By: TAM Subgroup of ADTC

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

Document Id: TAM148