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6.1.2.3 Other antidiabetic drugs

6.1.2.3 Other antidiabetic drugs

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 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®)
 
Liraglutide
Liraglutide is a treatment option for patients whose diabetes is not controlled with Metformin, and or sulphonylure and/or
glitazone. Patients prescribed liraglutide should be regularly reviewed and treatment should be in line with the recommedations 
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
 
Lixisenatide 
Lixisenatide is a treament option for all patients when a licensed GLP-1 mimetic is clinically indicated in line with SMC 
recommendation.
 
GREEN     Lixisenatide pre-filled pen  (Lyxumia®) 
                 50 micrograms/mL (10 micrograms/dose)
                 100 micrograms/mL,(20 micrograms/dose)
 
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
 
Semaglutide 
Semaglutide is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet
and exercise:
     >   as monotherpay when metformin is considered inappropriate due to intolerance or contraindications
     >   in addition to other medicinal products for the treatment of diabetes
See NICE Guideline  NG28
Please see Antihyperglycaemic guidelines
 
GREEN       Semaglutide (Ozempic®) 0.25mg, 0.5mg, 1mg solution for injection pre-filled pens.
 
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 60 ml/min/1.73 m2). 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®)
 
NICE TA597  Dapagliflozin with insulin as an option for treating Type 1 diabetes in adults with a body mass index (BMI) of at least
                     27kg/m², when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy, only if:
                       >    they are on insulin doses of more than 0.5 units/kg of body weight/day 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:
                                 º   how to recognise its risk factors, signs and symptoms
                                 º   how and when to monitor blood ketone levels
                                 º   what actions to take for elevated blood ketones, and
                       >     treatment is started and supervised by a consultant physician specialising in endocrinology and diabetes.
GREEN    Dapagliflozin 5 mg, 10 mg tablets (Forxiga®)                                                                                  CCG Commissioned
 
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,  canagliflozin should not be started in people with an eGFR of less than 60 ml/minute/1.73 m 2
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.
 
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) 
 
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                                                                                                                                               CCG Commissioned
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
 
NICE TA622 - Sotagliflozin                                                                                                                                               CCG Commissioned
Recommended as an option with insulin for treating Type 1 diabetes in adults with a body mass index of 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

 
 


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