6.1.2.3 Other antidiabetic drugs

Repaglinide & Nateglinide

Repaglinide and nateglinide stimulate insulin release. They have a rapid onset of action and short duration of activity,

and only need to be taken at mealtimes (shortly before each main meal). This makes them particularly useful alternatives

to sulphonylureas for patients with irregular meal patterns or lifestyles (where hypoglycaemia would otherwise pose a risk).

Repaglinide may be given as monotherapy for patients who are not overweight or for those in whom metformin is

contra-indicated or not tolerated, or it may be given in combination with metformin.

GREEN Nateglinide, tablets 60mg, 120mg, 180mg

GREEN Repaglinide, tablets 1mg, 2mg

Thiazolidinediones (Glitazones)

Glitazone Safety Concerns

Pioglitazone causes weight gain and increases the risk of heart failure (especially in combination with insulin).

It may also be worse in existing heart failure. Do not start or continue pioglitazone if the patient has current evidence or a

history or heart failure, or is at a higher risk of fracture. If prescribing pioglitazone, warn about significant oedema and tell

the patient what to do if this happens. Patients should be closely monitored for signs of heart failure. There are no

restrictions on the use of pioglitazone in acute coronary syndrome, ischaemic heart disease or peripheral arterial disease.

The European Committee on Medicinal Products for Human Use has recommended the suspension of the marketing

authorisations of Rosiglitazone (Avandia®) and it's combination product with metformin (Avandamet®) across the

European Union. Full details can be found under Drug Alerts & Withdrawals - Click Here

Pioglitazone to be prescribed in accordance with NICE guidance (CG87). LFT measurements are needed prior to treatment

and periodically thereafter. It should be remembered that control of modifiable cardiovascular risk factors such as smoking

cessation, lipids and blood pressure are the most important interventions to be made in patients with type II diabetes.

GREEN Pioglitazone tablets 15mg, 30mg, 45mg (generic only)

Intestinal alpha glucosidase inhibitor

Consider acarbose for a person unable to use other oral glucose-lowering medications. Delays the digestion and

absorption of starch and sucrose. Timing of doses is crucial: tablets should be chewed or swallowed whole with the first

mouthful of food.

GREEN Acarbose tablets 50mg, 100mg (Glucobay®)

Gliptins

GREEN Sitagliptin 25mg, 50mg,100mg tablets (Januvia®)

GREEN Linagliptin 5mg (Trajenta®)

GREEN Alogliptin 6.25mg, 12.5mg, 25mg tablets (Vipidia®)

Glucagon-like Peptide-1 agonists

Exenatide

It should be remembered that control of modifiable cardiovascular risk factors such as lipids and blood pressure are

the most important interventions to be made in patients with type II diabetes.

Consider adding exenatide to metformin and a sulfonylurea if a person has:

> a body mass index (BMI) ≥ 35 kg/m2 in those of European descent, with appropriate adjustment in tailoring this

advice for other ethnic groups and other specific psychological or medical problems associated with high body

weight

> a BMI < 35 kg/m2 and for whom initiation of insulin therapy would have significant occupational implications, or

where

> a weight loss would benefit other significant comorbidities such as sleep apnoea.

> Continue exenatide only if beneficial response occurs and is maintained (≥ 1.0 percentage point HbA1c reduction in 6

months and weight loss ≥ 5% at 1 year).

Exenatide is licensed for use with metformin, sulphonylurea and pioglitazone. Exenatide is not licensed for use with

any other oral antidiabetic drug. Up to 50% of patients experience nausea and vomiting, and due to its effects on slowing

gastric emptying, may interact with a variety of drugs including the contraceptive pill and antibiotics.

Exenatide 5mcg and 10mcg only is licensed as adjunct to basal insulin.

Exenatide 2mg is a long acting formulation administered once a week

GREEN Exenatide pre-filled pen 5 micrograms, 10 micrograms (Byetta®)

Exenatide 2mg pre-filled disposable syringe (Bydureon®)

GREEN Liraglutide[Victoza® pre-filled pen]

Liraglutide is a treatment option for patients whose diabetes is not controlled with Metformin, and or sulphonylurea

and/or glitazone. Patients prescribed liraglutide should be regularly reviewed and treatment should be in line with the

recommendations of NICE NG28 (replaced TAG203): only continue liraglutide if reduction in HbA1c of at least

1 percentage point and weight loss of at least 3% of initial body weight at 6 months. Liraglutide should only be used at a

maximum dose of 1.2mg daily, the 1.8mg/day dose should not be used.

GREEN Liraglutide pre-filled pen 18mg (Victoza®) PRESCRIBE BY BRAND

RED Liraglutide [Saxenda® solution for injection] Specialist medicine

NICE TA664 Recommended as an option for managing overweight and obesity alongside a reduced-calorie diet and

increased physical activity in adults, only if:

> they have a body mass index [BMI] of at least 35 kg/m2 (or at least 32.5 kg/m2 for members of minority ethnic

groups known to be at equivalent risk of the consequences of obesity at at a lower BMI than the white population) and

> they have non-diabetic hyperglycaemia (defined as a haemoglobin A1c level of 42 mmol/mol to 47 mmol/mol

[6.0% to 6.4%] or a fasting plasma glucose level of 5.5 mmol/litre to 6.9 mmol/litre) and

> they have a high risk of cardiovascular disease based on risk factors such as hypertension and dyslipidaemia and

> it is prescribed in secondary care by a specialist multidisciplinary tier 3 weight management service and

> the company provides it according to the commercial arrangement.

RED Liraglutide 6mg/ml solution for injection 3ml pre-filled pens [Saxenda®]

Dulaglutide

Appropriate for initiation and ongoing prescribing in both primary and secondary care when prescribed in the following

clinical circumstances (see NICE NG28):

> after second intensification of therapy fails to achieve targets combined with metformin and a sulfonylurea if the patient:

> has a BMI of >35kg/m2 and specific psychological or other medicinal problems associated with obesity

(adjust accordingly for people from black, Asian and other minority ethnic groups) or

> has a BMI <35kg/m2 and

> if insulin therapy would have significant occupational implications or

> if weight loss would benefit other significant obesity related comorbidities

Or, with specialist care advice and on going support from a consultant-led multidisciplinary team:

> combined with insulin at second intensification of treatment in patients who cannot take metformin

Dulaglutide may only be continued if the person has a beneficial metabolic response, defined as follows:

> a reduction of HbA1c by at least 11 mmol/mol [1.0%] and

> a weight loss of at least 3% of initial body weight in 6 months

GREEN Dulaglutide (Trulicity®)

0.75mg/0.5mL solution for injection/pre-filled pen

1.5mg/0.5mL solution for injection/pre-filled pen

3mg/0.5mL solution for injection/pre-filled pen

4.5mg/0.5mL solution for injection/pre-filled pen

Semaglutide solution for injection pre-filled pens [Ozempic®] CCG Commissioned

The GLP‑1 agonist Semaglutide is indicated in adults with type 2 diabetes mellitus to improve glycaemic control.

NICE Guideline 28 only recommends the prescribing of GLP‑1 agonists in the add-on therapy setting; therefore Semaglutide was reviewed only in the add-on therapy setting.

GREEN Semaglutide solution for injection pre-filled pens [Ozempic®] [in line with NICE Guideline 28]

Semaglutide tablets [Rybelsus®] CCG Commissioned

Semaglutide is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve

glycaemic control as an adjunct to diet and exercise.

GREEN (restricted) as an alternative GLP-1 receptor agonist for patients who are unable to use subcutaneous

formulations or patients who prefer oral administration. The effectiveness of semaglutide should be monitored 6

months after initiation in line with the targets below:

Semaglutide is an appropriate treatment option for initiation and ongoing prescribing in both primary and secondary care

when prescribed in the following clinical circumstances:

º after second intensification of therapy fails to achieve targets*:

° has a BMI of ≥35 kg/m2 and specific psychological or other medical problems associated with obesity (adjust

accordingly for people from Black, Asian and other minority ethnic groups) or

° has a BMI ˂ 35 kg/m2 and

¤ if insulin therapy would have significant occupational implications or

¤ if weight loss would benefit other significant obesity related comorbidities

Or, with specialist care advice and ongoing support from a consultant-led multidisciplinary team:

º combined with insulin at second intensification of treatment in patients who cannot take metformin

Semaglutide may only be continued if the person has a beneficial metabolic response, defined as follows:

º a reduction of HbA1c by at least 11 mmol/mol [1.0%] and

º weight loss of at least 3% of initial body weight in 6 months

See NICE Guideline NG28

Please also see Antihyperglycaemic guidelines

GREEN [restricted] Semaglutide tablets (Rybelsus®)

[see key]

SGLT2 Inhibitors NICE technology appraisals guidance (TA390)

Canagliflozin (Invokana,), Dapagliflozin (Forxiga,) and Empagliflozin (Jardiance,) are all selective sodium‑glucose

cotransporter 2 (SGLT‑2) inhibitors, which block the reabsorption of glucose in the kidneys and promote excretion of excess

glucose in the urine.

Through this mechanism these drugs may help control glycaemia independently of insulin pathways.

They all have UK marketing authorisations for treating type 2 diabetes to improve glycaemic control in adults:

> as monotherapy: when diet and exercise alone do not provide adequate glycaemic control in people for whom the

use of metformin is considered inappropriate due to intolerance or contraindications

> as add‑on combination therapy: with other glucose–lowering medicinal products including insulin, when these,

together with diet and exercise, do not provide adequate glycaemic control.

Dapagliflozin reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce

glucose reabsorption and increase urinary glucose excretion. Dapagliflozin is not recommended for people with moderate

to severe renal impairment (people with a creatinine clearance rate of less than 60 ml/min or an eGFR of less than

60ml/min/1.73m2)

For full details of adverse reactions and contraindications, see the summary of product characteristics.

GREEN Dapagliflozin (as propanediol monohydrate), 5 mg, 10 mg tablets (Forxiga®)

Canagliflozin

The recommended starting dosage of canagliflozin is 100 mg orally once daily. In people tolerating canagliflozin 100 mg

once daily who have an estimated glomerular filtration rate (eGFR) of at least 60 ml/minute/1.73 m² or creatinine clearance

of at least 60 ml/minute and who need tighter glycaemic control, the dose can be increased to 300 mg once daily.

For people with renal impairment, canagliflozinshould not be started in people with an eGFR of less than60 ml/minute/1.73 m²

or creatinine clearance of less than 60 ml/minute.

In people tolerating canagliflozin whose eGFR persistently falls below 60ml/minute/1.73m² or whose creatinine clearance

persistently falls below 60 ml/minute, the dose of canagliflozin should be adjusted to or maintained at 100 mg once daily.

Canagliflozin should be discontinued when eGFR is persistently below 45 ml/minute/1.73 m² or creatinine clearance is

persistently below 45 ml/minute.

A signal of increased lower limb amputation (primarily of the toe) in people taking canagliflozin compared with placebo

in a clinical trial in high cardiovascular risk patients is currently under investigation. Click here for prescribing advice.

GREEN Canagliflozin 100mg, 300 mg, tablets (Invokana®) as an option for Dual or Triple Therapy.

Dapagliflozin for treating chronic kidney disease as by NICE TA 775

Dapagliflozin is recommended as an option for treating chronic kidney disease [CKD] in adults.

It is recommended only if:

> it is an add-on to optimised standard care including the highest tolerated licensed dose of angiotensin-converting

enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), unless these are contraindicated, and

> people have an estimated glomerular filtration rate (eGFR) of 25 ml/min/1.73 m2 to 75 ml/min/1.73 m2 at the start of

treatment and:

> have type 2 diabetes or

> have a urine albumin-to-creatinine ratio [uACR] of 22.6 mg/mmol or more

GREEN Dapagliflozin tablets 5mg, 10mg [Forxiga] CCG Commissioned

Empagliflozin

The recommended starting dosage is 10 mg orally once daily for monotherapy. The dose can be increased to a maximum of

25 mg daily for people who tolerate empagliflozin well and need tighter glycaemic control, if they have an eGFR of

60 ml/min/1.73 m2 or more.

GREEN Empagliflozin 10mg, 25mg tablets (Jardiance®)

June 2017 - Position Statement (reference EMPA REG OUTCOME study)

Empagliflozin for treating chronic heart failure with reduced ejection fraction as by- NICE TA773

1. Empagliflozin is recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction

in adults, only if it is used as an add-on to optimised standard care with:

> an angiotensin-converting enzyme (ACE) inhibitor or angiotensin 2 receptor blocker (ARB), with a beta blocker and,

if tolerated, a mineralocorticoid receptor antagonist (MRA), or

> sacubitril valsartan with a beta blocker and, if tolerated, an MRA.

2. Start empagliflozin for treating symptomatic heart failure with reduced ejection fraction on the advice of a heart failure

specialist. Monitoring should be done by the most appropriate healthcare specialist

AMBER Empagliflozin 10mg, 26mg tablets [Jardiance®] CCG Commissioned

Ertugliflozin CCG Commissioned

NICE TA572 Ertugliflozin as monotherapy is recommended as an option for treating type 2 diabetes in adults for

whom metformin is contraindicated or not tolerated and when diet and exercise alone do not provide adequate

glycaemic control, only if:

> a dipeptidyl peptidase 4 (DPP‑4) inhibitor would otherwise be prescribed and

> a sulfonylurea or pioglitazone is not appropriate.

Ertugliflozin in a dual-therapy regimen in combination with metformin is recommended as an option for

treating type 2 diabetes, only if:

> a sulfonylurea is contraindicated or not tolerated or

> the person is at significant risk of hypoglycaemia or its consequences.

NICE TA583 Ertugliflozin with metformin and a dipeptidyl peptidase‑4 (DPP‑4) inhibitor is recommended as an option

for treating type 2 diabetes in adults when diet and exercise alone do not provide adequate glycaemic control,

only if:

> the disease is uncontrolled with metformin and a DPP-4 inhibitor, and

> a sulfonylurea or pioglitazone is not appropriate

GREEN Ertugliflozin (Steglatro®) 5mg, 15mg tablets

Sotagliflozin CCG Commissioned

NICE TA622 Recommended as an option with insulin for treating Type 1 diabetes in adults with a body mass index of at

at least 27kg/m², when insulin alone is does not provide adequate glycaemic control despite optimal insulin

therapy, only if:

> sotagliflozin is given as one 200 mg tablet daily

> they are on insulin doses of 0.5 units/kg of body weight/day or more and

> they have completed a structured education programme that is evidence based, quality assured,

delivered by trained

> educators and includes information about diabetic ketoacidosis, such as:

> how to recognise its risk factors, signs and symptoms

> how and when to monitor blood ketone levels

> what actions to take for elevated blood ketones and

GREEN Sotagliflozin (Zynquista®) * NOTE: as at 28.5.20 sotagliflozin is not yet available in the NHS

All material in this section is aimed at health care professionals, but is information currently held in the public domain, members of the

public seeking advice on medicine-related matters are advised to speak withtheir GP, pharmacist, nurse or contact NHS111 Service.

Email: info.elmmb@nhs.net