Case study: Tiredness, thirst and feeling unwell

How a drug safety alert helped to identify the cause of tiredness, thirst and feeling unwell in a patient with type 2 diabetes and other conditions.

A 56-year old man presented with a one week history of feeling out of sorts - tired, thirsty and unwell. He had an extensive past medical history and polypharmacy. 

He had type 2 diabetes for which he was on insulin, had ischaemic heart disease with a recent angioplasty and stenting, chronic back pain and spinal stenosis and essential hypertension. 

The patient’s symptoms for the last week included being tired, thirsty and feeling ill. There were no symptoms to indicate a chest or urinary infection, and there had been no recent changes to his medication, which consisted of:

  • metformin M/R 1g BD, dapaglifozin 10mg, insulin aspart 20u morning/22u evening, insulin glargine 80u night
  • clopidogrel 75mg, amlodipine 10mg, bisoprolol 10mg, nicorandil 10mg BD , pravastatin 40mg, aspirin 75mg, lisinopril 20mg
  • lansoprazole 30mg
  • morphine sulfate 10mg at night, tramadol 50mg PRN, nefopam 30mg 2 TDS

Of note he had to double his insulin requirements over the week, going to insulin aspart 42u/40u+ and insulin glargine 120u to maintain normal blood sugar readings.

Examination

Clinical examination was unremarkable. He was apyrexial. A urine dip showed a trace of ketones and nothing else. Bloods were requested , which showed normal white cell count and inflammatory markers. He had a small drop in his haemoglobin, but not enough to expect him to be symptomatically tired. There were no signs of underlying infection.

The reason for his symptoms and rapid and significant increase in Insulin requirements were a puzzle. It was our practice nurse lead for diabetes who came upon the answer. She had read of a drug safety update regarding SGLT2 inhibitors and the risk of diabetic ketoacidosis.1 The patient had been taking dapaglifozin since March 2014 and we advised him to stop his dapagliflozin immediately. 

Within two days he was back to normal, both symptomatically and with regard to his insulin needs. The incident was reported via the yellow card scheme.

Conclusion

SGLT2 (sodium glucose co-transporter 2) inhibitors are licensed for use in adults with type 2 diabetes. They include canaglifozin, dapagliflozin and empagliflozin. They work by blocking SGLT2 in the proximal tubule of the kidney.

SGLT2 is responsible for 90% of the glucose reabsorption from the proximal convoluted tubule, although a SGLT2 inhibitor inhibits 30-50% of glucose absorption in people with diabetes. Hence they promote glucose excretion. They have potential benefits of weight loss and blood pressure control as well as improved glycaemic control. Genital mycotic infection and increased urination are the most common side effects.

Serious cases of diabetic ketoacidosis (DKA) have been reported in patients taking this class of medication. Blood glucose levels may be only moderately elevated, although symptoms may fit with DKA and they may have ketones in the urine. Half of cases occurred within two months of starting the medication, but a small number occurred after stopping it. SGLT2 inhibitors are not licensed for use in Type 1 diabetes and cases have been reported in this group of individuals.

Advice for patients

Patients who start on this type of medication could be given ketosticks and a patient information leaflet on the signs and symptoms of DKA. These would include nausea and vomiting, anorexia, abdominal pain, confusion, unusual fatigue and excess thirst. If DKA is suspected, patients should be advised to stop SGLT2 inhibitor treatment, test for ketones and to seek medical help. 

Factors which may predispose patients on this medication to developing DKA include alcohol misuse, surgery, increased insulin need due to acute illness, a low beta cell function reserve and severe dehydration.

Practices may opportunistically advise patients on SGLT2 inhibitors about the risk of DKA and provide ketone testing strips. Practices may wish to run searches to see how many of their patients are on this medication and investigate the feasibility of calling them in to talk about the complication.

Management of DKA is detailed in useful web pages such as NICE clinical knowledge summariesor the Diabetes UK website.3

  • Dr Simon Gowda is a GP in Cheshire

Click here to take a test on this article and claim a certificate on MIMS Learning

References

  1. Medicines and Healthcare products Regulatory Agency (2015) SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin): risk of diabetic ketoacidosis
  2. CKS (2015) Insulin therapy in type 2 diabetes 
  3. Diabetes UK (2016) Diabetic ketoacidosis

Have you registered with us yet?

Register now to enjoy more articles and free email bulletins

Register

Already registered?

Sign in

Follow Us:

Just published

Oedema - red flag symptoms

Oedema - red flag symptoms

Red flag symptoms to be aware of when a patient presents with pitting or non-pitting...

Nine in 10 doctors fear NHS staff crisis could force them into mistakes

Nine in 10 doctors fear NHS staff crisis could force them into mistakes

Nine in 10 doctors fear a 'toxic combination' of rising workload and understaffing...

Proportion of GP practices with over 20,000 patients triples in five years

Proportion of GP practices with over 20,000 patients triples in five years

The proportion of GP practices in England with over 20,000 patients has more than...

Government's 'Yellowhammer' plan for no-deal Brexit confirms NHS fears

Government's 'Yellowhammer' plan for no-deal Brexit confirms NHS fears

Medicine shortages and an even tougher winter than usual lie ahead for the NHS should...

How GP trainee numbers in England have soared over the past decade

How GP trainee numbers in England have soared over the past decade

With serious concerns over the falling full-time equivalent (FTE) GP workforce in...

DHSC could shelve pension flexibility plans if Treasury overhauls annual allowance

DHSC could shelve pension flexibility plans if Treasury overhauls annual allowance

Plans to create the 'most flexible NHS pensions ever' could be shelved if the Treasury...