Patient Scenarios: CaReMeUK Guidance on the Management of Diabetes and Comorbidities

The following scenarios are fictitious but similar to those experienced by real patients and are designed to help you reflect on what you have learnt after reading the article. They could also be used for group discussion in an education or practice meeting. There are no right or wrong answers but some pitfalls to avoid.

The following case studies, written by Dr Umesh Dashora and colleagues from the Cardio–Renal–Metabolic Partnership, relate to their article Manage diabetes comorbidities with a joined-up strategy.

Case 1: Mike, 55 Years Old

Mike, a taxi driver, has had type 2 diabetes for 3 years. His most recent glycated haemoglobin (HbA_1c)measurement was 62 mmol/mol, and the previous measurement was 58 mmol/mol. He is already on the maximum dose of slow-release metformin (1 g twice daily).

Context

Mike has a body mass index (BMI) of 34 kg/m². He had one hospital admission in the preceding year for acute coronary syndrome (ACS). At the last retinopathy screen, he was found to have macular oedema.

Questions for Reflection

1. What would be the basis of your action?
2. What is your main advice for Mike?
3. What should you check before prescribing a medication?

How to Manage This Patient

1. NICE recommends a target HbA_1c of 48 mmol/mol for people with type 2 diabetes to reduce long-term complications. People with diabetes are at high risk of atherosclerotic cardiovascular disease (ASCVD) and associated mortality. Mike would benefit most from a medication that decreases his HbA_1c, but also that reduces his risk of major adverse cardiovascular events (MACE) given his recent history of ACS. Because he is a taxi driver, the medication should not increase his risk of hypoglycaemia, and because he is already overweight, the treatment should help him to lose weight 
2. Once we have reinforced diet and exercise advice, the main advice for Mike would be to add a sodium–glucose co-transporter 2 inhibitor (SGLT-2i) with evidence of a reduction in cardiovascular (CV) events. In people with type 2 diabetes and ASCVD, empagliflozin has been shown to significantly reduce the risk of MACE, hospitalisation for heart failure, and all-cause mortality. In people with or at high risk of ASCVD, canagliflozin has been shown to significantly reduce the risk of MACE, and dapagliflozin has been shown to significantly reduce the composite of death and hospitalisation for heart failure. A glucagon-like peptide 1 receptor agonist (GLP-1 RA) can be another good option after ACS, particularly in people with a high BMI. Neither of these medications causes hypoglycaemia, and body weight tends to decrease. Pioglitazone can also reduce ASCVD and does not cause hypoglycaemia, but it is contraindicated in the presence of macular oedema
3. Currently, empagliflozin can only be initiated if glomerular filtration rate (GFR) is ≥60 ml/min/1.73 m². Canagliflozin can be initiated in people with a GFR down to 45 ml/min/1.73 m². When we initiate any SGLT2i, we must warn the person with diabetes of a small (about 5%) risk of genital mycotic infection, which can be treated with over-the-counter medications. Diabetic ketoacidosis (DKA) can also occur rarely in circumstances that predispose individuals to DKA (such as starvation or alcohol abuse).

Case 2: Batty, 65 Years Old

Batty has had type 2 diabetes for 10 years. She has been taking gliclazide for the last 5 years, and her current dose is 160 mg twice daily. She is also on metformin 1 g twice daily. Her HbA_1c is 65 mmol/mol, and has increased since the last clinical review, when it was 58 mmol/mol. She does not like the idea of starting any injections that she will have to have daily. Her BMI is 40 kg/m². She is desperate to lose weight, but thinks that diabetes treatments will make her put on weight because, before starting gliclazide, her BMI was not that high.

Context

2 years ago, Batty was admitted with a fall and was diagnosed with transient ischaemic attack (TIA) and a fracture in the foot. She has a foot ulcer that is being dressed in the podiatry clinic regularly. She is also prone to recurrent genital infections.

Questions for Reflection

1. What other information would be useful?
2. Which second-line agent would be most appropriate?
3. What precautions should you take and what advice should you give to Batty?

How to Manage This Patient

1. It would be useful to know whether she is getting any hypoglycaemia with gliclazide. With her history of falls, it is important to review any medications that can increase the risk of hypoglycaemia and could lead to further falls
2. We should avoid SGLT2is because of her recurrent genital infections and foot problems. We should also try to stop or reduce her dose of gliclazide if there is further risk of hypoglycaemia. Pioglitazone is not appropriate because of its association with weight gain and fracture risk. One second-line option known to reduce the risk of stroke is a GLP-1 RA. Of the weekly GLP-1 RAs available, semaglutide and dulaglutide once weekly have the best evidence for reducing the risk of CV events, including stroke
3. GLP-1 RAs can initially cause nausea, which generally settles down gradually. If the side effects persist, we may have to choose another therapy.

Case 3: Abdul, 62 Years Old

Abdul has had diabetes for 8 years. He cannot tolerate metformin because of the associated gastrointestinal (GI) side effects. He is on gliclazide 160 mg twice daily, ramipril 10 mg once daily, and bisoprolol 2.5 mg once daily. At his annual review, his GFR was found to be 50 ml/min/1.73 m². It was previously normal. His HbA_1c is 64 mmol/mol.

Context

Abdul has had hypertension for 4 years and symptomatic heart failure with reduced ejection fraction (HFrEF) for 2 years. He also has haematuria and proliferative retinopathy. His BMI is 28 kg/m². He has been operated on for medullary thyroid cancer in the past. Both of his parents had myocardial infarction (MI) in their 60s. His uncle had urinary bladder cancer.

Questions for Reflection

1. What considerations are relevant in the selection of medications for Abdul?
2. What treatment would you choose?
3. How will you follow up?

How to Manage This Patient

1. Abdul is at high risk of adverse cardiac events, including hospitalisation for heart failure due to ethnicity, poor control of diabetes, and deteriorating renal function. His history of thyroid cancer precludes the use of a GLP-1 RA. Gliclazide increases the risk of hypoglycaemia, and should be used with caution. SGLT2is are not as effective for glucose lowering once GFR reduces below 45 ml/min/1.73 m². Pioglitazone is contraindicated with a history of heart failure and in the presence of haematuria until further tests exclude or confirm bladder cancer

2. Canagliflozin is currently licensed for initiation with a GFR down to 45 ml/min/1.73 m² (maximum dose 100 mg daily if eGFR is persistently <60 ml/min/1.73 m²). It can help to reduce MACE, hospitalisation for heart failure, and poor renal outcomes, and can be started in this scenario as long as caution is exercised with regard to hypoglycaemia. eGFR restrictions are likely to change with other SGLT2is. Many SGLT2is have shown impressive CV and renal protection. Please check the latest summaries of product characteristics (SPCs) because many more SGLT2is are likely to be licensed for use at lower eGFRs (indeed, SGLT2is are likely to be licensed and useful for their cardiorenal protective effects irrespective of HbA_1c). Gliclazide dose should be reduced to avoid the risk of hypoglycaemia. When diabetes control is not important or in people without diabetes, dapagliflozin can be used for persistent symptoms of heart failure despite standard treatments (including diuretics, angiotensin-converting enzyme [ACE] inhibition, beta blockers, and mineralocorticoid receptor antagonists [MRAs]). In this situation, dapagliflozin is licensed for use regardless of eGFR (usually avoid if eGFR <30 ml/min/1.73 m²). 

3. In view of his deteriorating eGFR, close follow up with monitoring of urea and electrolytes, full blood count (FBC), haematinics, bone profile, and HbA_1c may be needed every 3 months.

Case 4: Pam, 60 Years Old

Pam comes to the surgery with polydipsia, polyuria, and vaginal thrush. Blood tests show a plasma glucose level of 18 mmol/l, but there are no ketones in her urine or blood. Her renal function is normal, and her HbA_1c is 60 mmol/mol.

Context

Pam is known to the surgery; she suffers from inflammatory bowel syndrome (IBS) and has a foot ulcer. She was admitted last year to the local hospital with pancreatitis. Her total cholesterol is 6 mmol/l, with triglycerides 3.4 mmol/l. She takes regular treatment for hypertension and ischaemic heart disease (IHD). Her total cholesterol is 6 mmol/l, with triglycerides 3.4 mmol/l. Her BMI is 38 kg/m². She lives with her daughter and is independent for daily activities. Her father has type 2 diabetes.

Questions for Reflection

1. What are your thoughts?

2. What would be an appropriate medication for Pam?

How to Manage This Patient

1. Given her weight, age of onset, and metabolic profile, Pam is likely to have new-onset type 2 diabetes. She may not tolerate metformin given her history of IBS. SGLT2is are inappropriate because of her foot ulcer, although they may be considered when her foot ulcer heals and her thrush is resolved. A GLP-1 RA may not be the best choice given her history of pancreatitis. Rapid control of glucose levels is important because she is symptomatic
2. It would be appropriate to start with dual oral therapy with metformin and gliclazide. Metformin can be started in a small dose, for instance 500 mg daily, and then gradually increased by another 500 mg every week to a maximum tolerated dose. In the interim, gliclazide may be started at a dose of 40 mg twice daily, and quickly titrated up to control symptoms while keeping an eye on the risk of hypoglycaemia.

Case 5: Roger, 64 Years Old

Roger has type 2 diabetes, and comes to the GP surgery for his annual review. He takes metformin 1 g, linagliptin 5 mg, gliclazide 40 mg, ramipril 10 mg, diltiazem 120 mg, and atorvastatin 20 mg once a day. At a recent retinal screening, he was found to have moderate, non-proliferative diabetic retinopathy (DR).

Context

Roger is a current smoker of 20 cigarettes a day. His feet are free from any neuropathy or peripheral vascular disease. His BMI is 32 kg/m², HbA_1c 50 mmol/mol, blood pressure (BP) 135/85 mmHg, eGFR 40 ml/min/1.73 m², non-high-density-lipoprotein on atorvastatin 2.6 mmol/l, and albumin–creatinine ratio 40.

Questions for Reflection

1. How would you proceed?

How to Manage this Patient

1. The pattern of renal decline is important—what has changed in Roger’s eGFR and ACR over the last 2 years or so? The level of ACR elevation and eGFR are in line with the current licensed indication for canagliflozin 100 mg for renal protection in type 2 diabetes with chronic kidney disease (CKD). The renal benefit is independent of glycaemic lowering, and the addition of an SGLT2i would be indicated regardless. Roger’s BMI and BP may also benefit from the introduction of canagliflozin. Withdrawal of gliclazide may be necessary, and blood glucose monitoring may aid this.