His HbA1c is elevated at 64 mmol/mol despite taking 1g of metformin BD

A 64-year-old man with a history of type 2 diabetes comes to the clinic for review. His HbA1c is elevated at 64 mmol/mol despite taking 1g of metformin BD. On examination his blood pressure is 142/88 mmHg, his pulse is 82 beats per minute and regular. His body mass index is elevated at 33 kg/m². A decision is made to start him on dapagliflozin. Which of the following would you expect on starting therapy?

Increased blood pressure
Increased serum urate
Increased total cholesterol
Weight gain

SGLT-2 inhibitors like dapagliflozin promote increased glucose excretion because they inhibit glucose reabsorption in the kidney. This corresponds to a calorie load of 200-400 kcal per day. In some patients, this results in dramatic weight loss, although on average this equates to 1-2% reduction in weight over 6 months. SGLT-2 inhibitors are recognised to increased total cholesterol, (both HDL and LDL), although cardiovascular outcome studies as yet do not suggest this translates into increased risk of MACE events. In fact, the EMPA-reg study with empagliflozin demonstrated a reduction in overall mortality.

Hypoglycaemia is not a feature of SGLT2 inhibitor use and SGLT-2 inhibitors are associated with increased urate excretion rather than an increase in serum uric acid.