A quick guide to type 2 diabetes treatment

1. A quick guide to type 2 diabetes treatment Clare Bodey Claire Forrester

2. Case Study • A 45 year old male, who is otherwise well and has no past medical history, has presented with generalised tiredness. • He was found to have a fasting blood glucose of 14 mmol/l and a BMI of 33 • An HbA1c was done: 75 mmol/mol • Following a trial of 6 months of life style modification with diet and exercise his HbA1c remains at 64 mmol/mol • What will you do next?

3. Start Metformin Explain to your patient that you are going to start this treatment – what do you need to tell them about it?

4. Metformin • Suppresses hepatic gluconeogenesis & enhances peripheral glucose uptake. • Advantages: cheap, weight neutral, low risk of hypoglycaemic events. • Side effects: Gastrointestinal disturbance particularly diarrhoea • Cautions: Moderate renal failure, creatinine of <150/eGFR <30

5. Case cont…. • Following a few side effects you successfully manage these by changing to modified release metformin and repeat an HbA1c. • HbA1c 59 mmol/mol • What will you do next?

6. Start Sulfonylurea Explain to your patient that you are going to start this treatment – what do you need to tell them about it?

7. Sulfonylurea • Directly stimulate pancreatic beta cells. • Advantages: cheap, rapid therapeutic response, good for younger leaner patients, no CV risk • Disadvantages: weight gain and risk of hypoglycaemic events

8. Case cont… • Unfortunately this patient is having recurrent hypos. • What would you try instead of the sulfonylurea?

9. DPP-4 inhibitor (sitagliptin/vildagliptin) or Thiazolidinedione (pioglitazone) Explain to your patient that you are going to start this treatment – what do you need to tell them about it?

10. DPP4 - inhibitors • Inhibition of the DPP4 enzyme increases incretin (GLP-1 etc) production thus reducing glucagon production. • Can only be continued if there is a reduction in HbA1c by 0.5 points (about 5-6mmol/mol) over 6 months. • Advantages: weight neutral, low risk of having a hypo • Disadvantages: little long term evidence, caution CKD.

11. Thiazolidinedione • Work to reduce insulin resistance in liver & adipose tissue. • Can only be continued if there is a reduction in HbA1c by 0.5 points (about 5-6mmol/mol) over 6 months. • Needs 12 weeks for full efficacy • Advantages: low risk of hypos, can have combination tablets, potential decrease in CV risk due to effect on lipid profile • Disadvantages: weight gain likely, risk of fluid retention, some studies show increased fracture risk in female patients, longer term risk bladder cancer

12. Case cont… • Despite encouraging a continued exercise and diet plan and tolerating the medication well, a repeat HbA1c rises to 64 mmol/mol and he has gained weight with a BMI now 35. • What will you try next?

13. GLP – 1 analogue (exenatide, liraglutide) Explain to your patient that you are going to start this treatment – what do you need to tell them about it?

14. GLP-1 analogue • Works by mimicking incretin which stimulates insulin. • Can facilitate weight loss by slowing gastric emptying and reducing satiety. • Given by injection – short acting (repeated injections), long acting (daily injections) and new once weekly injections • Lower risk of hypos • Side effects: GI upset (all) which tend to improve over time.

15. GLP-1 analogues • Can be used if BMI ≥ 35, in people of European descent and there are problems associated with high weight. • Can be used if BMI <35, if insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities. • Can only be continued if reduction in HbA1c of at least 1% point and weight loss of at least 3% of initial body weight at 6 months.

16. Congratulations! • Your patient now has a HbA1c of 48 mmol/mol, a BMI of 30 and a fantastic quality of life.