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Diabetes care in Reading, Wokingham and West Berkshire

Treatment guidelines for Type 2 diabetes

Drug treatment used in the management of Type 2 diabetes

Core stepped approach to medical treatment of type 2 diabetes[i]

The recommended pathway for most patients is progression in treatment from metformin at step 1, adding a sulphonylurea (or newer agents for diabetes) at step 2 and adding isophane insulin at step 3. A target HbA1c of <59 mmol/mol is appropriate for most patients but there is a need to balance attempts to attain this with risks from hypoglycaemia[ii]. Each treatment steps should be reviewed at  4-6 months after change in therapy.

  • Individualised dietary and lifestyle education is the mainstay of therapy and should be tried for a period of 3 months before initialising drug therapy.
  • If patient <45 yrs OR BMI <25 consider virtual referral to community diabetologists or secondary care for investigation of other aetiology.


Step 1    HbA1c range >58mmol/mol

Start metformin at 500mg od, and titrate to 1g bd. Consider continuing at lower dose if GI side effects[iii].



A sulphonylurea can be used if metformin is contraindicated or not tolerated.

Pioglitazone[iv] 30 mg or DPP4 inhibitor[v] (currently Alogliptin 25mg od) are licensed for use as monotherapy, and can be used by patients who cannot take both metformin and sulphonylurea.



Step2      HbA1c >58mmol/mol after Step 1

Add sulphonylurea – usually gliclazide 80mg od, and titrate to max 160mg bd if required. Where hypoglycaemia is a risk or there is concern about weight gain, do not use a gliclazide.

Pioglitazone or DPP4 inhibitor can be added as a second drug to either metformin or sulphonylurea.


For BMI>30 Dapagliflozin is NICE-approved for addition to metformin only.



Step3     HbA1c still >58mmol/mol [vii]

HbA1c 59-85 mmol/mol Add 3rd oral or isophane insulin

HbA1c ≥85 mmol/mol add isophane insulin[viii] at night, or twice daily[ix]If BMI ≥35 consider Lixisenatide 10mcg increasing to 20mcg[x], and review oral therapies (e.g. stop SU or DPP4 inhibitor).

OR in patients with strong reason to avoid insulin (e.g. vocational driving licence) add 3rd oral

Treatment guidelines (printable)


Author Ian Gallen 2014-01-17


[i] Adapted from NICE guidelines


[ii] In some patients, a lower target might be appropriate but consideration should be given to the intensity of treatment. It would be inappropriate to aim for a lower target in patients with longstanding poor control. Intensive management of HbA1C in the elderly is not appropriate because of the risk of hypoglycaemia precipitating serious events in these patients.

[iii] Consider MR Metformin if poorly tolerated


[iv] Pioglitazone

Tablet with proven cardiovascular safety, but usually some weight gain.

Renal impairment: OK.

Side effects: weight gain, fluid retention.

Contraindications: heart failure, bladder cancer, haematuria, risk of osteoporosis.


[v] DPP-4 inhibitors (alogliptin, sitagliptin, vildagliptin, saxagliptin, linagliptin)

Tablet with no weight gain and few side effects, but long-term benefit not proven.

Renal impairment: OK, but reduced dose (see DPP4 guideline for detail).


[vi] Dapagliflozin as an alternative to sulphonylurea

NICE approved as add-on to metformin – but not as part of triple therapy, so would be stopped if then moving from dual to triple therapy.

Renal: avoid Dapagliflozin if eGFR<60; Dapagliflozin is not licensed for use with Pioglitazone


[vii] Average HbA1c reduction is about 11 mmol/mol with newer drugs, but may be individual variation, and some patients do show a greater response.


[viii] When HbA1c is very high, you will usually not achieve good control by adding one of these drugs. Insulin is preferred for patients with very poor control.


[ix] Insulin should be the usual option after metformin and sulphonylurea.

The newer drugs are aggressively marketed, but insulin remains a valuable therapy for type 2 diabetes and we have a huge amount of experience with it.

Insulin is “cleaner” and should be used in significant renal or hepatic impairment.

Insulin choice Insuman Basal, or Insuman Comb 15,25 or 50


[x] GLP-1 analogues (Lixisenatide exenatide, liraglutide).

Injection giving some weight loss, but long-term benefit not proven.

NICE: only if BMI>35, unless psychological or occupational reasons to avoid insulin.

Weight reduction – average 2-4kg, though significant individual variation.

Renal impairment: OK if eGFR >30

Side effects: nausea, bloating. Contraindications: risk of pancreatitis, bowel surgery.

Consider changing to Liraglutide if nauseous or sub-optimal response, or Bydureon if once weekly injection required.