Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction

doi:10.1016/j.pcd.2011.09.002

Primary Care Diabetes

Volume 6, Issue 1, April 2012, Pages 41-46

https://doi.org/10.1016/j.pcd.2011.09.002 Get rights and content

Abstract

Aims

To evaluate the effects of adding glucagon-like peptide-1 (GLP-1) analogue therapy to insulin on glycated hemoglobin (HbA1c), weight, insulin dosage, treatment satisfaction, and risk of hypoglycaemia.

Methods

Type 2 diabetes patients with insulin therapy receiving a GLP-1 analogue at 4 Swedish centers were studied. Hypoglycemia was evaluated using glucometers and patient self-report. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to evaluate treatment satisfaction.

Results

Among 65 patients studied, 4 discontinued therapy, none due to hypoglycemia, and there were no suspected severe adverse events. Among 61 patients who remained on therapy over a mean of 7.0 months, 40 were treated with liraglutide and 21 with exenatide. HbA1c decreased from a mean of 8.9% (82.4 mmol/mol) to 7.9% (71.9 mmol/mol) (p < 0.001), weight decreased from 111.1 kg to 104.0 kg (p < 0.001) and insulin doses were reduced from 91.1 U to 52.2 U (p < 0.001). There was one patient with severe hypoglycemia. The mean number of asymptomatic hypoglycemia per patient and month, reported for the last month (0.085 below 4.0 mmol/l and 0 below 3.0 mmol/l) and documented symptomatic hypoglycemia (0.24 below 4.0 mmol/l and 0.068 below 3.0 mmol/l) was low. The DTSQc showed higher treatment satisfaction than with the previous regimen of 11.9 (scale −18 to +18 points, p < 0.001).

Conclusions

The addition of GLP-1 analogues to insulin in patients with type 2 diabetes is associated with reductions in HbA1c, weight, and insulin dose, along with a low risk of hypoglycemia and high treatment satisfaction.

Introduction

Glucagon-like peptide-1 (GLP-1) analogues are novel antidiabetic agents associated with improvements in glycemic control and with low risk of hypoglycemia when used alone or together with metformin. GLP-1 analogues are also associated with reductions in weight, a high priority for many patients with diabetes [1], [2]. Their most common side effects are nausea and vomiting [3]. Among the two commercially available GLP-1 analogues [1], liraglutide (Victoza, Novo Nordisk) has been demonstrated to have a better effect on glycemic control and fewer side effects than exenatide (Byetta, Lilly/Amylin) in comparative randomized clinical trials [3].

Patients with poor glycemic control, increased body mass index (BMI), and using higher insulin doses are generally difficult to treat optimally due to insulin resistance and weight gain associated with increasing insulin dosages [4], [5]. In spite of a potential for improved metabolic control, there are limited data available on the use of GLP-1 analogues in patients on current insulin therapy, especially with respect to liraglutide [6], [7], [8], [9], although observational data on the use of liraglutide in combination with insulin in 15 patients with type 2 diabetes were recently reported [9]. A recent large clinical trial combined exenatide with insulin glargine [7], but there is a paucity of data on the effect of adding exenatide to patients treated with multiple daily insulin injections.

Despite these limited data, exenatide and liraglutide are used as add-on therapy to patients on different insulin regimens in clinical practice. Hence, there is a need to evaluate the efficacy and safety of these therapies. Therefore, we studied the effect of the addition of GLP-1 analogues on metabolic control and treatment satisfaction in a cohort of patients currently on insulin therapy.

Section snippets

Methods

Records of patients with type 2 diabetes treated at 3 hospital outpatient clinics and 1 primary care clinic in Sweden were retrospectively reviewed by the investigators and diabetic educators at the clinics until 20 December 2010. Since exenatide has been commercially available in Sweden since 2007, records prior to this date were excluded. This study was approved by the ethics committee of Gothenburg University, and all patients provided informed consent.

Variables of interest were glycated

Results

There were 65 patients studied between 2008–2010? Among all patients, 4 discontinued GLP-1 analogue use, 2 for nausea, 1 for fatal myocardial infarction, and 1 for acute sepsis affecting the liver. None discontinued due to hypoglycemia. Patient characteristics at baseline of the 61 patients continuing with GLP-1 analogues are given in Table 1.

Glycemic control was generally poor in the study population, with a mean HbA1c of 8.9% (82.4 mmol/mol). Patients were generally overweight or obese (mean

Discussion

In this observational study of adding GLP-1 analogues to patients on insulin therapy in clinical practice, we demonstrated improvements in glycemic control. At the same time, in this patient group commonly difficult to optimally treat in the presence of obesity and high insulin doses, weight decreased and insulin dosages were reduced. Rates of hypoglycemia were low, and patients reported hypoglycemic problems to be lower with the combination of GLP-1-analogue and insulin than insulin alone in

Conflict of interest

ML has served as consultant or received honoraria from Eli Lilly, Novo Nordisk Scandinavia, Novartis, Pfizer and Sanofi-Aventis, been in the advisory board of Novonordisk Scandinavia and received research grants from Astra Zeneca and Novonordisk Scandinavia. JJ has participated in advisory boards; Eli Lilly, NovoNordisk, Boehringer Ingelheim, Pfizer. Participation in clinical trials; Eli Lilly, NovoNordisk, Sanofi-Aventis, Roche. OT has had lectures for Novonordisk Scandinavia and participated

Acknowledgements

We would like to thank Anette Nilsson at Karlstad Hospital and Helen Bove at Uddevalla Hospital who were central to the data collection process.

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Intensive blood–glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
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There are more references available in the full text version of this article.

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Original researchGlucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction

Abstract

Aims

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conflict of interest

Acknowledgements

Lancet

Clin. Ther.

Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis

BMC Endocr. Disord.

Willingness to pay for health improvements associated with anti-diabetes treatments for people with type 2 diabetes

Curr. Med. Res. Opin.

Intensive blood–glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

Lancet

Insulin-associated weight gain in diabetes – causes, effects and coping strategies

Diabetes Obes. Metab.

Glucagon-like peptide-1 analog and insulin combination therapy in the management of adults with type 2 diabetes mellitus

Ann. Pharmacother.

Original research
Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction