Dr Sharon Rees@reesprescribe
Day 1: In the mid 19th century, phlorizin extracted from the root bark of the apple tree was found to cause glycosuria; there was poor oral absorption and also, because non-selective, the inhibition of gut SGLT1 led to unpleasant gut side-effects. Synthesis of analogues in the 1990s led to #dapagliflozin licensed by EMA in 2012.
Dr Sharon Rees@reesprescribe
Day 2: Indications are for primary diabetes mellitus as monotherapy (T2DM) or in combination with insulin for T1DM or T2DM. Dose 5 mg (T1) or 10 mg (T2) once daily. #dapagliflozin is also routinely combined with other hypoglycaemic agents eg metformin. NICE TA597 (2020) outlines strict guidance for #dapagliflozin use in T1DM, including BMI ≥27kg/m2 and providing education about ketoacidosis.
Dr Sharon Rees@reesprescribe
Day 3: #dapagliflozin has good oral absorption and bioavailability with high protein binding. Metabolised by phase 2 glucuronidation (minor CYP activity) with renal excretion of inactive metabolites-t½ 14hrs. Monitor renal function throughout & don't start if eGFR<60 60 mL/minute/1.73 m2/avoid if <45.
Dr Sharon Rees@reesprescribe
Day 4: MOA; the sodium glucose cotransporter 2 (SGLT2) manages 90% of glucose reabsorption in proximal convoluted tubule. Inhibition of the transporter by #dapagliflozin leaves glucose in ˛ ltrate for excretion in urine. The calorie loss supports HbA1c reduction and weight loss. #dapagliflozin can affect urinary loss of an average of 300 calories/day. This translates to an average body weight loss of 2.7% (higher than for metformin).
Dr Sharon Rees@reesprescribe
Day 5: #dapagliflozin adverse drug events; common include genital infections, back pain, ketoacidosis (T1DM), dyslipidaemia, increased risk infection, urinary disorders. Uncommon are constipation, volume depletion, rarely Fournier's gangrene. Low risk hypos (not exhaustive).
Dr Sharon Rees@reesprescribe
Day 5 (cont): Diabetic ketoacidosis with #dapagliflozin can occur in T2DM, but is only ‘common’ in T1DM. Putative pathway is lowered blood glucose (from SGLT2is) > reduced insulin levels. This leads to the release of free fatty acids into citric acid cycle to increase energy and accumulation of acid by-products and metabolic acidosis. Risk factors for ketoacidosis include alcohol consumption, sub-optimal insulin dosing or increased insulin need, dehydration, caloric restriction.
Dr Sharon Rees@reesprescribe
Day 6 : Drug-drug interactions for #dapagliflozin; ‘moderate’ only and almost all are other hypoglycaemic agents having an additive effect, or drugs which have an additive hypotensive effect eg amlodipine, bisoprolol.
Dr Sharon Rees@reesprescribe
Day 7: Sodium, as well as glucose transport, is inhibited by SGLT2i's such as #dapagliflozin; therefore, less sodium is reabsorbed causing osmotic diuresis. The impact on circulating volume, BP, pre/afterload has cardiovascular bene˛ ts. Recent UK approval for heart failure (rEF).
EARN YOUR CPD CERTIFICATE
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
Complete the additional reading suggested below and then answer the ten questions. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A,B,C,D option. If you achieve 8 or more out of ten on the questions, a CPD certificate will be emailed to you.
Dapagliflozin is a chemical derivative from the cherry tree
TRUE or FALSE?
Which of the following is TRUE?
- You have to take dapagliflozin with food
- dapagliflozin cannot be combined with insulin
- dapagliflozin is a highly selective and potent sodium glucose cotransporter 2 inhibitor (SGLT2i)
- dapagliflozin is only licensed for use in type 2 diabetes mellitus
- dapagliflozin undergoes extensive phase 1 CYP450 breakdown TRUE or FALSE?
It is important to monitor renal function throughout use
TRUE or FALSE?
Which of the following is FALSE?
- dapagliflozin mainly works in the proximal convoluted tubule
- Sodium and glucose are both inhibited from reabsorption from dapagliflozin
- dapagliflozin usually has some weight loss effect
- You should avoid initiating dapagliflozin if the eGFR is <80
The high concentration of glucose in the urine encourages urinary tract infections
TRUE or FALSE?
Which of the following is NOT a risk factor for ketoacidosis?
- Alcohol consumption
- Has COPD as a comorbidity
- Dehydration
- Missed insulin dose
Dapagliflozin has cardiovascular benefits
TRUE or FALSE?
Dapagliflozin has multiple severe drug-drug interactions
TRUE or FALSE?
Further reading on #dapagliflozin
Diabetes: https://bnf.nice.org.uk/treatment-summary/diabetes.html
Type 2 diabetes: https://bnf.nice.org.uk/treatment-summary/type-2-diabetes.html
dapagliflozin: https://bnf.nice.org.uk/drug/dapagliflozin.html
Forxiga 10 mg film-coated tablets: https://www.medicines.org.uk/emc/product/7607/smpc