The timely initiation and titration of insulin is a challenge for many healthcare professionals involved in the treatment of T2DM. The failure to do so when clinically indicated is a multifactorial problem with significant consequences for patients, including an increased risk of microvascular complications.

Barriers to insulin initiation and intensification include the inconvenience of the treatment regimen, needle phobia, and fear of hypoglycaemia. These barriers can be compounded by patient factors such as poor health literacy, lack of social support, and financial constraints. Healthcare professionals play a vital role in addressing these barriers through patient education, individualised support, and shared decision-making.

Basal insulin and analogues

Optimal basal insulin therapy entails an insulin analogue that mimics the natural basal endogenous insulin secretion profile, ensuring consistent and efficacious glycaemic control. Basal insulin analogues produced through recombinant DNA technology represent a significant advance over Neutral Protamine Hagedorn (NPH) insulin, an intermediate-acting insulin still in use today despite its requirement for twice-daily dosing and relatively high risk of hypoglycaemia.

The first generation of basal insulin analogues, namely insulin glargine 100 units/mL (Gla-100) and insulin detemir 100 units/mL, offered near 24 hour glucose-lowering effects with minimal variability in insulin action and a lower hypoglycaemia incidence than NPH insulin.

The newer second-generation basal insulin analogues, insulin glargine 300 units/mL (Gla-300) and insulin degludec 100 units/mL (IDeg U100) or 200 units/mL (IDeg U200), exhibit extended durations of action and evenly distributed activity profiles. They are associated with reduced hypoglycaemia rates and maintain HbA1C control comparable to earlier basal analogues. Additionally, they offer the convenience of once-daily dosing and decreased interindividual variability.

Despite the advent of insulin analogues, improved insulin regimens, enhanced injection devices, promotion of early insulin initiation, and continuous titration algorithms, many individuals with T2DM continue to struggle with inadequate glycaemic control.

Basal plus

To enhance glycaemic control, individuals with suboptimal control on a basal insulin regimen can transition to a basal-plus insulin approach. This entails adding a short- or rapid-acting insulin before the largest meal or the one causing the most post-meal glucose spikes. Insulin doses are titrated based on self-monitoring glucose levels before subsequent meals.

Gradually, additional insulin doses are introduced for meals associated with post-meal hyperglycaemia, ultimately forming a complete basal-bolus regimen. Concurrently, oral agents, excluding metformin, are gradually phased out to simplify the regimen.

When to initiate insulin

Indications for insulin therapy in non-pregnant adults encompass various scenarios related to T2DM. This includes initiating insulin treatment at the time of diagnosis or during any stage when there is evident metabolic decompensation. Such decompensation can be characterised by several factors, including significant weight loss due to catabolism, fasting plasma glucose levels that exceed 14mmol/l, consistently elevated random glucose levels surpassing 16.5mmol/l, HbA1C levels exceeding 10%, and the presence of persistent ketogenesis, ketoacidosis, or a hyperosmolar non-ketotic state.

For stable patients who are not experiencing metabolic decompensation, insulin becomes a viable treatment option under different circumstances. It should be considered when these individuals struggle to achieve or maintain adequate glycaemic control despite the use of two or more alternative anti-diabetic agents. These guidelines help guide healthcare professionals in determining when insulin therapy is appropriate for non-pregnant adults with T2DM.

What influences patient choice?

For patients with T2DM who cannot or are unwilling to adhere to basal plus/basal-bolus regimens, premixed insulin is the best option. Patient-reported outcomes (PROs) should be assessed before and during treatment to ensure patient-centred care. PROs include quality of life, satisfaction, diabetes-related distress, anxiety and depression, coping skills, and the quality of communication between the healthcare provider and patient.

A patient’s overall health is a critical factor in determining the suitable insulin formulation. Analogue insulins hold an advantage due to their lower hypoglycaemia risk compared to human insulins. For those with busy, unpredictable lifestyles, the flexibility to align insulin administration with the main daily meal enhances convenience and adherence.

IDegAsp is a valuable choice for initiating insulin therapy in several scenarios. This includes drug-naïve patients displaying hyperglycaemic symptoms, individuals with high-carb diets, those with elevated HbA1c levels, and concerns about post-meal blood sugar spikes. It’s also an option when oral anti-diabetic medications (single, dual, or triple therapies) prove ineffective.

Consistent meal schedules are vital for achieving glycaemic goals. Yet, dietary patterns may vary based on work obligations and religious practices, like Ramadan, which can affect glycaemic control and insulin usage in individuals with diabetes. During religious fasting, premixed insulin analogues, known for their efficacy and lower hypoglycaemia rates, are preferred over premixed human insulins. IDegAsp may be the favoured choice for individuals fasting during Ramadan, highlighting the importance of risk assessment and counselling for these individuals.

REFERENCES

1. Chun J, et al. Insulin Initiation and Titration in Patients With Type 2 Diabetes. Diabetes Spectr, 2019 May;32(2):104-111.
2. Kalra S, et al. Insulin initiation: bringing objectivity to choose. J Diabetes Metab Disord, 2015 Mar 25;14:17.
3. Nauck MA, et al. Treatment of type 2 diabetes: challenges, hopes, and anticipated successes. Lancet Diabetes Endocrinol, 2021; 9: 525–44.
4. Swinnen SG, et al. Insulin therapy for type 2 diabetes. Diabetes Care, 2009 Nov;32 Suppl 2(Suppl 2):S253-9.
5. The Society for Endocrinology, Metabolism and Diabetes of South Africa. Type 2 Diabetes Guidelines Expert Committee, 2017. The 2017 SEMDSA Guideline for the Management of Type 2 Diabetes Guideline Committee. JEMDSA, 2017; 21(1)(Supplement 1): S1-S196.