Dr. Jarvis (London, England)

Let us meet our first patient: he is very similar, I suspect, to many patients that you have met in the past; even if you haven't seen him personally, I'm sure you have seen somebody like him. So, let us think about his position.

This gentleman is 67 years old, so not exactly old but not young either. He retired two years ago and is now spending more time gardening and caravanning. Hurrah for him. Of course, the problem with that is that caravanning includes driving. And if he was coming towards you at 50 miles/hour on the other side of a road, not just in a car but with a caravan behind him, then I think you would have need to be very concerned if he was having a hypoglycaemic event. We often think of people who are driving as those who perhaps drive for work, either professionally as taxi drivers or those who drive long distances in order to get to work, but so many of us are reliant on cars these days. And the impact of hypoglycaemia on driving should not be underestimated.

He's had T2D for 10 years, he has a history of hypertension, his kidney function is beginning to decline and, not surprisingly at this stage after 10 years, he has mild, non‑proliferative retinopathy. But he also was previously on glimepiride. He recently had some tests, which I'll show you in a minute, but he decided to stop his own glimepiride before he got the results because he was concerned about the symptoms that he was having and he realised that they might be due to his glimepiride.

So, he's now taking metformin and empagliflozin, ramipril and simvastatin. His control is not optimal. His HbA_1c is 7.5%, his blood pressure 136/86, his eGFR [shows] early stage 3a kidney disease with a UACR of 3 mg/mmol. His LDL, at least, is well controlled.

This was what was happening when he was taking his sulphonylurea: you can see that he was having significant episodes of hypoglycaemia and, of course, it's entirely possible that he had hypoglycaemia unawareness. We know that increasing age, deteriorating renal function, longer duration of diabetes and previous hypos all increase the risk of hypo unawareness, which in turn greatly increases the risk of severe hypoglycaemia. But he has stopped his sulphonylurea because of his ‘funny turns’ , which we can see were quite clearly due to his sulphonylurea.

I would suggest we should be looking at an HbA_1c less than 7%, we should be trying to reduce his risk of hypoglycaemic episodes by not restarting his sulphonylurea and, of course, I would suggest it's not appropriate to give him the other drug that could cause hypos, which is insulin. And we should be considering controlling his blood pressure.

So why do I think that linagliptin would be a good option for Mr X? Well, firstly, he was previously on glimepiride (on a sulphonylurea) and in terms of glucose lowering, linagliptin is likely to be comparable with glimepiride. This is a durable drug; it has good long-term efficacy, we can see here 0.6% reduction at 104 weeks. We also, of course, can expect him to lose a little bit of weight and 80% of people with T2D are overweight or obese so that would be welcome. Even 1.5 or 2 kg is not insignificant. Then, of course, with linagliptin, more patients achieved HbA_1c targets without hypoglycaemic events and without gaining weight compared to glimepiride.

Finally, we know that this is a man who is at high risk of CV events. He’s male, he's 67, he’s had T2D for 10 years, his blood pressure is not optimally controlled, even if his cholesterol is. And we need a drug that does not give him an increased risk of CV disease. We know that regardless of the patient profile, linagliptin quite clearly is not associated with any significant increase in the risk of CV events.

So, given that linagliptin is the first approved DPP4 [inhibitor] that does not require dose reduction based on kidney function and therefore we do not need to worry about the fact that his kidney function is declining, certainly from the perspective of drug dosage or drug safety for linagliptin, I would argue that this is a highly suitable drug.

We added in amlodipine 5 mg once daily and in addition added linagliptin. The results were gratifying. So, linagliptin can help to simplify patient management: it is proven to be efficacious, it has an established safety profile and for this patient with early deterioration in renal function, the once daily, one dose regimen, which will not require adjustment if his renal function changes, is to be welcomed. Multifactorial management, of course, is highly important.