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Retrospective analysis of safety and efficacy of insulin-to-liraglutide switch in Japanese type 2 diabetes: A caution against inappropriate use in patients with reduced β-cell function.

Usui R, Yabe D, Kuwata H, Fujiwara S, Watanabe K, Hyo T, Yasuhara A, Iwasaki M, Kitatani N, Kuwabara K, Yokota K, Kurose T, Seino Y - J Diabetes Investig (2013)

Bottom Line: In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co-administration, body mass index, duration and total daily insulin dose.The switch also significantly reduced the percentage of body fat and visceral fat areas.However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST-ΔCPR.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes, Clinical Nutrition and Endocrinology Kansai Electric Power Hospital Osaka Japan.

ABSTRACT

Aims/introduction: The safety and efficacy of insulin-to-liraglutide switch in type 2 diabetes has not been studied adequately. Here, we retrospectively characterize clinical parameters that might predict insulin-to-liraglutide treatment switch without termination due to hyperglycemia, and examine the effects of switching the therapies on glycated hemoglobin (HbA1c) and bodyweight in Japanese type 2 diabetes.

Materials and methods: Japanese type 2 diabetes patients who underwent the switch of therapy were evaluated for their clinical data including β-cell function-related indices, such as increment of serum C-peptide during glucagon stimulation test (GST-ΔCPR). HbA1c and bodyweight were analyzed in patients continuing with liraglutide after switching from insulin for 12 weeks.

Results: Of 147 patients, 28 failed in the switch due to hyperglycemia, nine failed because of other reasons and 110 continued with liraglutide for the 12-week period. Patients failing in the switch due to hyperglycemia showed longer duration and higher daily insulin dose, as well as lower GST-ΔCPR. Receiver-operating characteristic analysis showed that GST-ΔCPR of 1.34 ng/mL is a cut-off point for insulin-to-liraglutide switch without termination due to hyperglycemia. In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co-administration, body mass index, duration and total daily insulin dose. The switch also significantly reduced the percentage of body fat and visceral fat areas.

Conclusions: Insulin-to-liraglutide switch can improve glycemic control and reduce bodyweight in Japanese type 2 diabetes patients. However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST-ΔCPR.

No MeSH data available.


Related in: MedlinePlus

Predictors for insulin‐to‐liraglutide switch without liraglutide termination due to hyperglycemia. (a) Indices related to β‐cell function were compared in patients who failed in the switch due to hyperglycemia within 12 weeks (n = 28) and patients who continued liraglutide for 12 weeks after the switch (n = 110). The increment of serum C‐peptide levels before and 6 min after i.v. administration of 1 mg glucagon (GST‐ΔCPR), and C‐peptide index (CPI) defined as (fasting CPR [ng/mL]) / (fasting plasma glucose [(mg/dL)]) × 100 are compared. Each value represents mean ± standard error of the mean. **P < 0.01 in unpaired t‐test (vs patients with liraglutide continued for 12 weeks after the switch). (b) Receiver–operating characteristic curves of serum C‐peptide immunoreactivity (CPR)‐0 min, CPR‐6 min and GST‐ΔCPR to predict insulin‐to‐liraglutide switch without termination of liraglutide due to hyperglycemia. Areas under the curve for CPR‐0 min, CPR‐6 min and GST‐ΔCPR were 0.730, 0.784 and 0.812, respectively. Cut‐off points for CPR‐0 min, CPR‐6 min, GST‐ΔCPR, and CPI were determined as 1.07, 1.94, 1.34 ng/mL and 0.93, respectively.
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jdi12111-fig-0001: Predictors for insulin‐to‐liraglutide switch without liraglutide termination due to hyperglycemia. (a) Indices related to β‐cell function were compared in patients who failed in the switch due to hyperglycemia within 12 weeks (n = 28) and patients who continued liraglutide for 12 weeks after the switch (n = 110). The increment of serum C‐peptide levels before and 6 min after i.v. administration of 1 mg glucagon (GST‐ΔCPR), and C‐peptide index (CPI) defined as (fasting CPR [ng/mL]) / (fasting plasma glucose [(mg/dL)]) × 100 are compared. Each value represents mean ± standard error of the mean. **P < 0.01 in unpaired t‐test (vs patients with liraglutide continued for 12 weeks after the switch). (b) Receiver–operating characteristic curves of serum C‐peptide immunoreactivity (CPR)‐0 min, CPR‐6 min and GST‐ΔCPR to predict insulin‐to‐liraglutide switch without termination of liraglutide due to hyperglycemia. Areas under the curve for CPR‐0 min, CPR‐6 min and GST‐ΔCPR were 0.730, 0.784 and 0.812, respectively. Cut‐off points for CPR‐0 min, CPR‐6 min, GST‐ΔCPR, and CPI were determined as 1.07, 1.94, 1.34 ng/mL and 0.93, respectively.

Mentions: Baseline characteristics of the patients who were followed closely for the 12‐week period are shown in Table 1. Despite the fact that unnoticed lifestyle changes might significantly influence the failure rate later, the safety of the therapy switch might well be apparent within this period. Of these 147 patients, 28 failed in the switch due to hyperglycemia within 12 weeks, nine failed due to other reasons indicated in Materials and Methods, and 110 continued on liraglutide for the 12‐week period. The logistic analysis showed that estimated duration, baseline HbA1c and total daily insulin dose were significantly associated with the failure due to hyperglycemia (Table S1). In addition, withdrawal of non‐SU antidiabetic drugs was not significantly associated with failure due to hyperglycemia. The proportion of patients who failed in the insulin‐to‐liraglutide switch due to hyperglycemia was higher in patients with increased baseline HbA1c, longer duration of type 2 diabetes and higher total daily insulin dose, but was not affected by BMI or frequency of insulin injections (Figure S1). The indices related to β‐cell function were significantly reduced in patients who failed in the insulin‐to‐liraglutide switch due to hyperglycemia (Figure 1a). ROC analyses were carried out for CPR‐0 min, CPR‐6 min, GST‐ΔCPR and CPI to characterize their relevance to the success of the insulin‐to‐liraglutide switch. GST‐ΔCPR showed the largest AUC (0.812, 95% confidence interval [CI] 0.703–0.920), with a cut‐off point estimated to be 1.34 ng/mL with 59% sensitivity and 95% specificity (Figure 1b and Table 2).


Retrospective analysis of safety and efficacy of insulin-to-liraglutide switch in Japanese type 2 diabetes: A caution against inappropriate use in patients with reduced β-cell function.

Usui R, Yabe D, Kuwata H, Fujiwara S, Watanabe K, Hyo T, Yasuhara A, Iwasaki M, Kitatani N, Kuwabara K, Yokota K, Kurose T, Seino Y - J Diabetes Investig (2013)

Predictors for insulin‐to‐liraglutide switch without liraglutide termination due to hyperglycemia. (a) Indices related to β‐cell function were compared in patients who failed in the switch due to hyperglycemia within 12 weeks (n = 28) and patients who continued liraglutide for 12 weeks after the switch (n = 110). The increment of serum C‐peptide levels before and 6 min after i.v. administration of 1 mg glucagon (GST‐ΔCPR), and C‐peptide index (CPI) defined as (fasting CPR [ng/mL]) / (fasting plasma glucose [(mg/dL)]) × 100 are compared. Each value represents mean ± standard error of the mean. **P < 0.01 in unpaired t‐test (vs patients with liraglutide continued for 12 weeks after the switch). (b) Receiver–operating characteristic curves of serum C‐peptide immunoreactivity (CPR)‐0 min, CPR‐6 min and GST‐ΔCPR to predict insulin‐to‐liraglutide switch without termination of liraglutide due to hyperglycemia. Areas under the curve for CPR‐0 min, CPR‐6 min and GST‐ΔCPR were 0.730, 0.784 and 0.812, respectively. Cut‐off points for CPR‐0 min, CPR‐6 min, GST‐ΔCPR, and CPI were determined as 1.07, 1.94, 1.34 ng/mL and 0.93, respectively.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4020254&req=5

jdi12111-fig-0001: Predictors for insulin‐to‐liraglutide switch without liraglutide termination due to hyperglycemia. (a) Indices related to β‐cell function were compared in patients who failed in the switch due to hyperglycemia within 12 weeks (n = 28) and patients who continued liraglutide for 12 weeks after the switch (n = 110). The increment of serum C‐peptide levels before and 6 min after i.v. administration of 1 mg glucagon (GST‐ΔCPR), and C‐peptide index (CPI) defined as (fasting CPR [ng/mL]) / (fasting plasma glucose [(mg/dL)]) × 100 are compared. Each value represents mean ± standard error of the mean. **P < 0.01 in unpaired t‐test (vs patients with liraglutide continued for 12 weeks after the switch). (b) Receiver–operating characteristic curves of serum C‐peptide immunoreactivity (CPR)‐0 min, CPR‐6 min and GST‐ΔCPR to predict insulin‐to‐liraglutide switch without termination of liraglutide due to hyperglycemia. Areas under the curve for CPR‐0 min, CPR‐6 min and GST‐ΔCPR were 0.730, 0.784 and 0.812, respectively. Cut‐off points for CPR‐0 min, CPR‐6 min, GST‐ΔCPR, and CPI were determined as 1.07, 1.94, 1.34 ng/mL and 0.93, respectively.
Mentions: Baseline characteristics of the patients who were followed closely for the 12‐week period are shown in Table 1. Despite the fact that unnoticed lifestyle changes might significantly influence the failure rate later, the safety of the therapy switch might well be apparent within this period. Of these 147 patients, 28 failed in the switch due to hyperglycemia within 12 weeks, nine failed due to other reasons indicated in Materials and Methods, and 110 continued on liraglutide for the 12‐week period. The logistic analysis showed that estimated duration, baseline HbA1c and total daily insulin dose were significantly associated with the failure due to hyperglycemia (Table S1). In addition, withdrawal of non‐SU antidiabetic drugs was not significantly associated with failure due to hyperglycemia. The proportion of patients who failed in the insulin‐to‐liraglutide switch due to hyperglycemia was higher in patients with increased baseline HbA1c, longer duration of type 2 diabetes and higher total daily insulin dose, but was not affected by BMI or frequency of insulin injections (Figure S1). The indices related to β‐cell function were significantly reduced in patients who failed in the insulin‐to‐liraglutide switch due to hyperglycemia (Figure 1a). ROC analyses were carried out for CPR‐0 min, CPR‐6 min, GST‐ΔCPR and CPI to characterize their relevance to the success of the insulin‐to‐liraglutide switch. GST‐ΔCPR showed the largest AUC (0.812, 95% confidence interval [CI] 0.703–0.920), with a cut‐off point estimated to be 1.34 ng/mL with 59% sensitivity and 95% specificity (Figure 1b and Table 2).

Bottom Line: In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co-administration, body mass index, duration and total daily insulin dose.The switch also significantly reduced the percentage of body fat and visceral fat areas.However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST-ΔCPR.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes, Clinical Nutrition and Endocrinology Kansai Electric Power Hospital Osaka Japan.

ABSTRACT

Aims/introduction: The safety and efficacy of insulin-to-liraglutide switch in type 2 diabetes has not been studied adequately. Here, we retrospectively characterize clinical parameters that might predict insulin-to-liraglutide treatment switch without termination due to hyperglycemia, and examine the effects of switching the therapies on glycated hemoglobin (HbA1c) and bodyweight in Japanese type 2 diabetes.

Materials and methods: Japanese type 2 diabetes patients who underwent the switch of therapy were evaluated for their clinical data including β-cell function-related indices, such as increment of serum C-peptide during glucagon stimulation test (GST-ΔCPR). HbA1c and bodyweight were analyzed in patients continuing with liraglutide after switching from insulin for 12 weeks.

Results: Of 147 patients, 28 failed in the switch due to hyperglycemia, nine failed because of other reasons and 110 continued with liraglutide for the 12-week period. Patients failing in the switch due to hyperglycemia showed longer duration and higher daily insulin dose, as well as lower GST-ΔCPR. Receiver-operating characteristic analysis showed that GST-ΔCPR of 1.34 ng/mL is a cut-off point for insulin-to-liraglutide switch without termination due to hyperglycemia. In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co-administration, body mass index, duration and total daily insulin dose. The switch also significantly reduced the percentage of body fat and visceral fat areas.

Conclusions: Insulin-to-liraglutide switch can improve glycemic control and reduce bodyweight in Japanese type 2 diabetes patients. However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST-ΔCPR.

No MeSH data available.


Related in: MedlinePlus