Novo Nordisk has released new clinical data showing that the reduced weight gain seen with Levemir (insulin detemir), its long-acting insulin analogue for the treatment of diabetes, can be sustained over a period of two years.

The data were presented at the 43rd annual meeting of the European Association for the Study of Diabetes (EASD) in Amsterdam this week. The weight advantages observed in a succession of clinical trials with Levemir were further validated by a sub-group analysis of the PREDICTIVE 303 study, which found that diabetes patients switched to Levemir from standard NPH insulin or insulin glargine (Lantus, Sanofi-Aventis) actually lost weight.

Levemir’s ability to achieve blood glucose targets without the degree of weight gain experienced by diabetics taking – and especially starting on – other basal insulins has been a key differentiator for the Novo Nordisk brand, most of all in relation to its more established long-acting rival Lantus.

The weight benefit is also an important consideration in expanding the insulin market and optimising the effectiveness of current treatments. The new Levemir data were highlighted at a press briefing in Amsterdam to launch Weight of the World, a report sponsored by Novo Nordisk that assesses the global threat posed by ‘diabesity’ – obesity and diabetes combined – and urges doctors and patient not to accept weight increase as the inevitable price of glycaemic control.

As the report points out, the fear or reality of gaining weight are a significant barrier to both treatment initiation and adherence with insulin. Moreover, the authors maintain, even a relatively modest weight loss can improve blood glucose control and reduce the risk of further complications such as heart disease.

While 13 out of 13 published clinical trials have shown a weight benefit with Levemir versus other basal insulins, the 24-month study in Type 1 diabetes presented at the EASD meeting was the first long-term comparison of a modern basal insulin with the commonly used NPH insulin, Novo Nordisk pointed out.

Two-year study

The open-label, parallel group trial in 10 countries examined the long-term efficacy and safety of Levemir and NPH insulin, both in combination with mealtime insulin aspart (IAsp), in Type 1 diabetics using a treat-to-target concept. A total of 497 men and women were randomised to Levemir (331) or NPH (166).

After two years the NPH + IAsp group had gained an average of 2.7 kg in body weight, compared with a 1.7 kg increase in the Levemir + IAsp group. Blood glucose levels as measured by HbA1c were 7.36% in patients taking Levemir and 7.58% in those on NPH insulin, with reductions in HbA1c of 0.9% and 0.7% respectively. The American Diabetes Association recommends an HbA1c level of less than 7.0% to minimise the risk of severe complications including heart disease, blindness, amputations, nerve damage and kidney failure.

Moreover, 22% of the Levemir group reached the HbA1c target of around 7% in the absence of confirmed hypoglycaemia during the last month of treatment, against 13% in the NPH insulin group. The risk of major and nocturnal hypoglycaemia was respectively 69% and 46% lower with Levemir than with NPH.

PREDICTIVE 303

The PREDICTIVE 303 data came from a US study in 5,604 patients with Type 2 diabetes that assessed the effectiveness of Levemir over six months using a simplified self-adjusted dosing algorithm, as opposed to standard-of-care physician-driven adjustments.

The subgroup analysis involved switching 1,663 patients who were previously on insulin glargine (i.e., Lantus) with or without oral antidiabetic drugs (OADs) and 310 patients who were on NPH insulin with or without OADs to Levemir with or without OADS following randomisation.

In the patients switched from Lantus to Levemir, HbA1c levels in both groups combined (i.e., self-adjusted dosing and physician-driven adjustments) dropped from a mean 8.4% at baseline to 8.1% at 26 weeks, while patients switched from NPH to Levemir showed an HbA1c reduction from 8.3% to 8.1%.

There was again an improvement in hypoglycaemia, measured in terms of event/patient/year on the basis of episodes reported for the four weeks prior to each study visit. In the Lantus to Levemir group, the rate of hypoglycaemia was down from 10.1 at baseline to 6.6 at 26 weeks; in NPH to Levemir patients it fell from 12.1 to 7.0 at 26 weeks.

The PREDICTIVE 303 analysis also provided further evidence of Levemir’s weight advantage over other basal insulins. In patients switched from Lantus to Levemir, mean body weight dropped from 98.9 kg at baseline to 98.2 kg at 26 weeks and in the NPH to Levemir group it came down from 97.2 kg to 95.7 kg.

As one of the PREDICTIVE 303 researchers, Luigi Meneghini of the Diabetes Research Institute at the University of Miami Miller School of Medicine in the US, noted in Amsterdam, the consistent reductions in weight gain seen with Levemir in randomised controlled trials have also translated to a ‘real-world’ setting.

The ongoing PREDICTIVE observational study is evaluating the safety and efficacy of Levemir in routine clinical practice, a task that involves more than 35,000 patients in over 20 countries. In the European cohorts, Levemir has been associated with weight loss in both Type 1 and Type 2 diabetes, with additional reductions in weight seen when patients on NPH insulin or Lantus were switched to Levemir.