Achieving Control in Type 2 Diabetes

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
Patient factors	<25kg/m²OR osmotic symptoms of hyperglycaemia. If weight loss check ketones.	>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 therapy (monotherapy)	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)
Second-line oral therapy (dual therapy)	SU + MET	MET + ONE of the following:
		DPP-4 inhibitors ("gliptins") Choose if weight gain and/or hypos are a concern.*	SU Choose if BMI <27kg/m²	PIOGLITAZONE (PIO) Choose if BMI <27kg/m² and/or hypos are a concern.* See PIO prescribing algorithm.		SGLT2 inhibitors** ("flozins") Choose if weight gain and/or 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) or consider injectable therapy eg insulin in BMI <30kg/m², GLP1 therapy** if BMI >30kg/m²
		DPP-4 inhibitors ("gliptins") Choose if weight gain and/or hypos are a concern.*	SU Choose if BMI <27kg/m²		PIO Choose if BMI <27kg/m² and hypos are a concern.* See PIO prescribing algorithm.	SGLT2 inhibitors** ("flozins") Choose if weight gain and/or hypos are a concern.* Note, do not initiate if eGFR <60ml/min.
GLP-1 therapy	Not appropriate	GLP1 may also be used with insulin: stop DPP-4 consider reduction of SU dose on initiation can continue metformin can continue SGLT2 inhibitor ("flozin") refer to GLP-1 protocol for further information.
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 insulin (risk of fluid retention) Consider reducing or stopping SU
	* Falls in the elderly, driving, occupation, alcohol consumption. ** Favour SGLT2 inhibitors and GLP1 receptor agonists in individuals with known cardiovascular disease.
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 (5mg if severe hepatic impairment)	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.