You review a 57-year-old man that is currently taking a combination of standard-release metformin, gliclazide and pioglitazone for the management of his type 2 diabetes. His most recent HbA1c was 65 mmol/mol. He is tolerating the drugs well.  He frequently has blood glucose readings greater than 18 mmol/l. He is considerably overweight (BMI 38), and drives a lorry for a living.

  1. What does NICE recommend as the first-line drug in the treatment of diabetes?
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If the HbA1c is >48 mmol/mol with lifestyle modification alone, then drug treatment is recommended. The current NICE and SIGN guidelines both advise that standard-release metformin is used as the initial drug treatment for adults with type 2 diabetes.

If metformin is contraindicated or not tolerated, initial drug treatment with one of the following should be considered:

  • A dipeptidyl peptidase‑4 (DPP‑4) inhibitor, or;
  • A thiazolidinedione (pioglitazone), or;
  • A sulfonylurea.


  1. Which drug treatments do NICE recommend for the 1st and 2nd intensification of drug treatment in diabetes?
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The NICE recommendations for intensification of drug therapy are as follows: 

1st intensification of drug treatment if HbA1c >58 mmol/mol. Consider dual therapy, aiming for an HbA1c target of 53 mmol/mol, with one of:

  • Metformin plus pioglitazone
  • Metformin plus sulfonylurea
  • Metformin plus dipeptidyl peptidase-4 (DPP4) inhibitor
  • Metformin plus sodium-glucose co-transporter 2 (SGLT2) inhibitor


2nd intensification of drug treatment if HbA1c >58 mmol/mol. Consider triple therapy, aiming for an HbA1c target of 53 mmol/mol, with one of:

  • Metformin plus pioglitazone plus sulfonylurea
  • Metformin plus sulfonylurea plus DPP4 inhibitor
  • Metformin plus pioglitazone, or sulfonylurea, plus SGLT2 inhibitor
  • Insulin-based treatment


  1. What further treatment can be considered in this patient?
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This patient’s diabetes is poorly controlled despite using metformin, a sulfonylurea and pioglitazone. He is having regular episodes of marked hyperglycaemia and his HbA1c level is also poorly controlled. Insulin would be a possible alternative, but weight loss would be beneficial, and insulin would have implications on his career, therefore at this stage, the addition of a glucagon-like peptide-1 (GLP1) analogue would be the most appropriate option.

NICE recommend that if triple therapy is ineffective, not tolerated, or contraindicated consider a GLP1 analogue as follows:

  • Metformin plus sulfonylurea plus GLP1 analogue, if BMI >35, or if BMI <35 and insulin has significant implications and weight loss would benefit obesity-related conditions
  • Only continue with GLP1 analogue if HbA1c is lowered by 11 mmol/mol and there is >3% weight loss in 6 months



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