Globally it is estimated that approximately 7.5 per cent of people with type 2 diabetes require insulin therapy and data from the National Diabetes Audit in the UK indicates that approximately 10 per cent of people with type 2 diabetes are on insulin, despite increased use of GLP1 agonists and SGLT2 inhibitors in recent years, which means fewer people are treated with insulin than in the past. Often those people with type 2 diabetes on insulin, due to their underlying insulin resistance, require high doses of basal insulin, which can become increasingly ineffective as the dose response curve starts to flatten out once doses exceed about 30 units.
When basal insulin doses exceed about 60 units daily or post-prandial glucose levels are poorly controlled then bolus insulin is often added, either with particular meals where carbohydrate content is greatest and/or glucose peaks are most marked, or with all meals, but the same problem occurs when higher doses of bolus insulin are required. The availability of higher-concentration insulins, such as U200 insulin degludec (Tresiba) and lispro (Humalog), and U300 insulin glargine (Toujeo), mitigates the flattening of the dose response curve to some extent, by increasing the insulin dose at which the curves start to flatten out.
However, those people with type 2 diabetes who require very high doses of insulin often have poor glycaemic control which does not respond particularly well to escalating doses, and the high insulin doses are commonly associated with marked weight gain in people who are usually significantly obese to begin with. Furthermore, insulin doses, particularly at mealtime, may be insufficient, due to underestimation of the carbohydrate content of the meal, or missed completely, adversely impacting glycaemic control. Administration of insulin by smart pens or insulin pumps can help address some of these issues that perpetuate suboptimal glycaemic control.
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Smart insulin pens
Studies with smart insulin pens have highlighted the frequency of missed insulin doses – as well as providing a means to avoid these instances happening. One study with 75 participants, including 16 older people aged over 65 type 2 diabetes, found 24 per cent of bolus and 36 per cent of basal insulin doses were non-adherent, with those in the least-adherent tertile missing 50 per cent of bolus doses and having significantly worse glycaemic control, a mean HbA1c of 8.6 per cent vs 7.7 per cent in the most-adherent tertile.
We have found using the NovoPen 6 smart insulin pen to be particularly useful in older people with type 2 diabetes on insulin treatment who have cognitive issues, which means they cannot remember whether or not they have administered an insulin injection. Moreover, this can be helpful for carers who may not be present when a dose is due but can give it at a later time if the dose has been missed. The ability to review all insulin doses that have been given by uploading data from the smart pen can also make for a more meaningful clinic consultation and give greater security when adjusting an insulin regimen. In pregnant women with type 2 diabetes, the combination of a smart pen and continuous glucose monitoring, for example with the Freestyle Libre, allows them to better appreciate the efficacy of their bolus dosing and enhances their ability to get time in target range (3.5-7.8 mmol/L) to over 90 per cent.
Insulin pump therapy
Insulin pump therapy is well established as an option for intensive insulin therapy in type 1 diabetes with meta-analysis highlighting its potential to give superior glycaemic control over multiple daily injection regimens. Hybrid-closed loop therapy, combining insulin pump therapy and continuous glucose monitoring to automate basal insulin delivery, is increasingly the preferred option for people with type 1 diabetes, with the National Institute for Health and Care Excellence (NICE) publishing guidance recommending this for people with type 1 diabetes who have an HbA1c above 7.5 per cent on multiple daily injection regimens, as well as all women pregnant or planning pregnancy and all children.
In contrast, national consensus guidelines, such as those from NICE, generally do not recommend the use of insulin pump therapy in people with type 2 diabetes. However, when multiple daily injections with high doses of insulin are ineffective in helping achieve target HbA1c for a person with type 2 diabetes, insulin pump therapy may be the best option for trying to improve glycaemic control. The largest randomised controlled trial of insulin pump therapy in type 2 diabetes, the OpT2mise study, randomised 331 people with type 2 diabetes on multiple daily insulin analogue injections (MDI) and with an HbA1c of 8.0 per cent or above to six months of insulin pump therapy or continued MDI.
The mean HbA1c in both groups was 9.0 per cent at baseline but fell by 1.1 per cent in the pump arm compared to 0.4 per cent in the MDI arm; the mean insulin dose fell from 112 to 97 units daily in the pump arm but increased from 106 to 122 units in the MDI arm. There was a small increase in weight in both groups which did not differ significantly between groups. Fifty-five per cent of pump users achieved an HbA1c < 8.0 per cent compared to 28 per cent in the MDI arm. A meta-analysis of randomised controlled trials of pump therapy in people with type 2 diabetes poorly controlled on MDI confirmed a similar effect across these studies, with the HbA1c improved by 0.4 per cent more in the pump arm, alongside a drop in insulin dose of 24 units daily; the higher the starting HbA1c or the insulin dose the greater the fall in that parameter.
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Our experience of insulin pump therapy in type 2 diabetes has been very similar to that reported in these trials. We have used it for people with poor glycaemic control on insulin doses over 200 units and achieved reductions in HbA1c of over 2 per cent with insulin requirements falling by more than 50 per cent, in most cases the reduction in the insulin requirement more than covering the cost of the pump. We have also used insulin pump therapy in people with type 2 diabetes for more specific indications: insulin allergy, pregnancy and gastroparesis.
The main benefit of insulin pump therapy in type 2 diabetes appears to relate to more reliable absorption and hence consistent dosing with delivering basal insulin continuously rather than as large once or twice daily doses. Prandial glucose management has been less problematic, and this is reflected by the relative lack of glycaemic variability in most people with type 2 diabetes even when on multiple daily injections. There are published data supporting the use of hybrid closed loop systems in type 2 diabetes with significant improvements in glycaemic control over the use of MDI alone, but there is no evidence that these systems offer any benefit over pump therapy alone.
References available on request.
Dr. Peter Hammond, MD FRCP, is a Consultant Endocrinologist at Harrogate and District NHS Foundation Trust in the UK.