A cost-controlling treatment strategy of adding liraglutide to insulin in type 2 diabetes.

BACKGROUND: Addition of the GLP-1 receptor agonist liraglutide to insulin can reverse insulin-associated weight gain, improve HbA1c and decrease the need for insulin, but is expensive. From a cost perspective, such treatment should be discontinued when it is clear that treatment targets will not be achieved. Our aim was to find the best cost-controlling treatment strategy: the shortest possible trial period needed to discriminate successfully treated patients from those failing to achieve predefined targets of treatment success. METHODS: We used data from the 'Effect of Liraglutide on insulin-associated wEight GAiN in patients with Type 2 diabetes' (ELEGANT) trial, comparing additional liraglutide (n = 47) and standard insulin therapy (n = 24) during 26 weeks, to calculate the costs associated with different trial periods. Treatment success after 26 weeks was defined by having achieved ≥ 2 of the following: ≥ 4% weight loss, HbA1c ≤ 53 mmol/mol (7%), and/or discontinuation of insulin. RESULTS: The additional direct costs of adding liraglutide for 26 weeks were € 699 per patient, or € 137 per 1 kg weight loss, compared with standard therapy. The best cost-controlling treatment strategy (identifying 21 of 23 responders, treating four non-responders) was to continue treatment in patients showing ≥ 3% weight loss or ≥ 60% decrease in insulin dose at 8 weeks, with a total cost of € 246 for this t rial period, saving € 453 in case of early discontinuation. CONCLUSION: An 8-week trial period of adding liraglutide to insulin in patients with insulin-associated weight gain is an effective cost-controlling treatment strategy if the liraglutide is discontinued in patients not showing an early response regarding weight loss or insulin reduction.

Durable efficacy of liraglutide in patients with type 2 diabetes and pronounced insulin-associated weight gain: 52-week results from the Effect of Liraglutide on insulin-associated wEight GAiN in patients with Type 2 diabetes' (ELEGANT) randomized controlled trial.

BACKGROUND: Pronounced weight gain frequently complicates insulin therapy in patients with type 2 diabetes (T2DM). We have previously reported that addition of liraglutide for 26 weeks can reverse insulin-associated weight gain, decrease insulin dose and improve glycaemic control, as compared with continuation of standard insulin treatment. OBJECTIVES: To investigate whether the beneficial effects of liraglutide are sustained up to 52 weeks and whether similar effects could be obtained when liraglutide is added 6 months later. METHODS: Adult T2DM patients with ≥ 4% weight gain within 16 months of insulin therapy completing the first 26-week trial period of open-label addition of liraglutide 1.8 mg day(-1) (n = 26) versus continuation of standard insulin therapy (n = 24) were all treated with liraglutide for another 26 weeks. Results were analysed according to the intention-to-treat principle. RESULTS: Overall, 24 (92%) and 18 (75%) patients originally assigned to liraglutide and standard therapy, respectively, completed the study. Addition of liraglutide decreased body weight to a similar extend when given in the first 26 weeks (liraglutide group) or second 26 weeks (original standard therapy group): -4.4 vs. -4.3 kg (difference -0.32 kg, 95% confidence interval -2.2 to 1.6 kg; P = 0.74). Similar results were also seen in the two groups with regard to decrease in haemoglobin A1c (HbA1c ) (-0.77 vs. -0.66%; P = 0.23) and insulin dose (-28 vs. -26 U day(-1) ; P = 0.32). In both groups, 22% of patients could discontinue insulin. Continuation of liraglutide until 52 weeks led to sustained effects on body weight, HbA1c and insulin-dose requirements. CONCLUSION: In T2DM patients with pronounced insulin-associated weight gain, addition of liraglutide within 2 years leads to sustained reversal of body weight, improved glycaemic control and decrease in insulin dose. Thus, liraglutide offers a valuable therapeutic option.

Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.

AIMS/HYPOTHESIS: Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. METHODS: We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. RESULTS: As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1ß after 6 months of insulin therapy compared with those who had not gained weight. CONCLUSIONS/INTERPRETATION: We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00781495. FUNDING: The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.