The first option for patients with diabetes should indeed be lifestyle modification and metformin. Metformin is currently favoured as a first-line treatment due to its low cost and efficacy, although newer therapies such as SGL2-inhibitors and GLP-1 receptor agonists are challenging its dominance. Generally, the only reason to stop metformin therapy is the onset of severe side effects.
When it comes to choosing a secondary agent, the best options presented by our current crop of medicines are the SGLT-2 Inhibitors and GLP-1 agonists. The secondary treatment agents are especially important if the presence of any of the following can be confirmed: atherosclerotic cardiovascular disease, heart failure or chronic kidney disease.
If your patients present with any of these conditions, SGLT-2 inhibitors or GLP-1 RAs are called for. For atherosclerotic cardiovascular disease, a GLP-1 RA is favoured, while SGLT-2 inhibitors are often prescribed for CKD or heart failure.
CASE STUDY: BRIAN
Brian, a person living with diabetes for the last 10 years, take 1g metformin twice daily, dapagliflozin 10mg daily and a 60mg dose of modified-release gliclazide daily. He is also hypertensive and hyperlipaemic, with a strong family history of coronary artery disease. After clinical assessment, it was determined that Brian suffers from sensorimotor peripheral neuropathy and has a BMI of 32kg/m2.
Tests determined that Brian has an HbA1c of 8.2%. Brian’s LDL cholesterol is at 8.2mmol. According to the European Society of Cardiology’s guidelines, if a patient has established cardiovascular disease, their LDL levels have to ideally be below 1.4mmol. An LDL under 1.0mmol is ideal for patients without pronounced cardiovascular comorbidities.
Brian is obese and at increased cardiovascular risk. When encountering a patient like this, it should be kept in mind that cardiovascular death is responsible for approximately 80% of all deaths in T2DM patients. In Brian’s case, a GLP-1 RA is a very attractive option, since we’re likely to see some weight loss, a lower risk of hypoglycaemia compared with a basal insulin, and an increased probability of good adherence to therapy, since the newer generation GLP-1 RAs come in a once-weekly formulation.
If, however, Brian’s medical aid refuses to pay for his GLP-1 RA treatment, he can be started on a basal insulin. Brian should continue taking his oral therapy, and be moved onto an analogue basal insulin or ultra-long-acting basal analogue insulin. He should also be speedily referred to a diabetic nurse educator.
Brian should start with a low dose of insulin (approximately 8 to 10 units), preferably at night after supper. If he prefers, he can instead inject in the morning, provided it’s an analogue insulin and he takes it at roughly the same time each day. Dr Jairam recommends the simple titration method. Using this method, Brian would aim for a fasting glucose level between 4.0 and 7.0mmol/litre. If above target, he can increase his insulin dose by two units. If below target, he can subtract 2 units.
If Brian’s HbA1c is above 7%, despite having optimal fasting glucose levels, it might be time to add a GLP-1 RA to his treatment regimen. Alternatively, one might have to change to a fixed-ratio combination or proceed to intensifying his insulin therapy.
CASE STUDY: SUNNY
Sunny is 50 years old and has lived with diabetes for the past 12 years. He takes metformin 1mg a day, dapagliflozin at the maximum dose of 10mg a day, and 50 units of insulin glargine daily. He has two main meals: breakfast and supper. He has optimised his diet and exercises three times a week. His HbA1c levels hover around the 8.4% mark.
Sunny wears a continuous glucose monitor and measures his glucose levels prior to his meals, as well as two hours thereafter, for three days. This provides a good overview of a patient’s glucose levels. Sunny’s readings indicate a predominance of post-prandial hypoglycaemia. Since Sunny is already taking a large dose of basal insulin, GLP-1 RAs won’t contribute much to achieving a HbA1c under 7%.
The options for treating Sunny are therefore whether to put him on a premix insulin or a basal bolus regimen. In Sunny’s case, the analogue premix insulin is preferred. Either way, it is vital that he continues his metformin and dapagliflozin treatment. He should take half his dose approximately 10 minutes before breakfast and the other half 10 minutes before supper.
To be safe, Sunny should stop his basal insulin regimen and start on the premix insulin 24 hours later. This will reduce the risk of insulin stacking and hypoglycaemia. Sunny should aim for premeal glucose levels of 4.0 to 7.0mmol/litre. If he is at target pre-breakfast, he should take the same dose pre-supper. If his pre-breakfast levels are above 7.0mmol/litre, he should increase his pre-supper levels by 2 units every three days.
If Sunny’s glycaemic targets are not met, despite him using more than 1 unit of insulin per kg per day, his treatment has to be re-evaluated. Many patients on premix insulin find that they develop mid-morning hypoglycaemia if they try to increase their pre-breakfast doses. The options for intensifying his therapy would include taking premix insulin three times a day (not recommended since it is difficult to titrate), adding a short-acting basal insulin at lunch, or switching to a basal bolus regimen. It is also key to ensure that Sunny is using his non-insulin-based therapies optimally.
For further case studies of Rita, Kerry and Harry, as well as tips for titrating basal bolus insulin and insulin lispro, visit bit.ly/3zKfCzD for a full recording of Dr Jairam’s webinar.