Dr.Akanksha Singh
Aug 26, 2017 · 4 min read

Glucagon-like peptide-1 analogues and risk of Breast cancer in women with Type 2 diabetes

A recent 2016 by UK demonstrates that the use of Glucagon- like peptide -1 Analogues in Type 2 Diabetes women can increase the risk of breast cancer. The purpose of this study was mainly to examine the effect of 2 glucose lowering drugs — Glucagon- like peptide -1 Analogues & Dipeptidylpeptidase –4 inhibitors on developing breast cancer.

GLP-1 Analogues & DPP-4 Inhibitors are incretin based drugs used as 2nd or 3rd line treatment for type 2 diabetes mellitus. These drugs are incretin based drugs which help to help control to post meal blood sugar levels. The term incretin refers to a hormone or peptide that reduce glucose release into blood after a meal via various mechanisms. Therefore, these drugs increase the levels of incretin in our body thereby controlling blood sugar levels. DPP-4 Inhibitors ( Sitagliptin, Saxagliptin, Linagliptin) are oral medicines for type 2 diabetes whereas GLP-1 Analogues ( Exenatide, Liraglutide) are injectable medicines. Although these drugs As they are weight neutral or induce weight loss in this mostly overweight population, they are popular among clinicians and patients alike. Nonetheless, concerns have been raised about GLP-1, that their use could increase the risk of certain malignancies such as pancreatic cancer and mainly Breast cancer. GLP-1 receptors are located on normal breast tissue and it is suggested that the use of GLP-1 analogues could promote tumour growth factor; it is known to be a breast cancer gene and its association with increased breast cancer risk.

A new study published in the British Medical Journal mainly demonstrates a comparative analysis between the use of Glucagon- like peptide -1 Analogues & Dipeptidylpeptidase –4 inhibitors with the increased risk of incidence of breast cancer. This study was conducted by the use of the UK Clinical Practice Research Datalink (CPRD).The researchers tracked almost 44984 women aged atleast 40 years who were newly treated with blood sugar reducing medications between 1st January 2007 and 31st March 2015 with follow up until 2016; to examine the onset of breast cancer. Patients who were excluded out of this study were the one who were prescribed Insulin, women with Polycystic Ovarian Syndrome, Gestational Diabetes, previously diagnosed with breast cancer or the ones who died or left the study before 31st March 2016. The women who were prescribed incretin — based therapy were followed till 31st March 2016.The study mainly depended on the THREE FACTORS — overall use of GLP-1 Analogues, total duration of the use of this drug and time since the drug was started.

Patients were then divided into 3 groups as the one prescribed on GLP-1 Analogues ( Exenatide, liraglutide & lixisenatide, alone or in combination with other blood sugar reducing medicines), secondly on DPP-4 Inhibitors ( Sitagliptine, Saxagliptine and Vildagliptine, alone or in combination with other blood sugar reducing medicines) and lastly the other blood sugar reducing medicines. Based on the above categorisation the patients were analysed on the basis of the use of GLP-1 analogues in terms of total duration of use of GLP-1 analogue and the time since the drug was started.

Analysis of the data showed that 44 984 patients were followed for 3.5 years, out of which 2473(5.5% ) patients were on glucagon- like peptide-1 analogues, amongst these 1071(43.3%) liraglutide users, 792 (32%) exenatide users , 98(4%) lixisenatide users & 512 (20.7%) who used multiple GLP-1 analogues during the follow up time. Overall there were 549 cases of breast cancer which were recorded during the study. In comparison to DPP-4 Inhibitors , GLP-1 analogues use was associated with 1.4 times the rate of breast cancer incidence per year , whereas DPP-4 inhibitors use was (4.4 vs 3.4 per 1000 persons years). 1071 Liraglutide users & 792 Exenatide users were separately examined and their incidence rate were 1.51 & 1.33 times per yearly rate of breast cancers , respectively. The third survey which was basically relating to time ; the use of GLP-1 analogues for 2.1 -3 years showed an increased risk of breast cancer by 2.66 times. This pattern was again observed between 3.1–4 years with an increased risk of breast cancer incidence by 2.62 times than that of the use of DPP-4 inhibitors.

The results of this study showed no link between the use of GLP-1 analogues with an overall increased risk of breast cancer.. This study also had some limitations regarding the duration of follow up which could be considered to short to investigate cancer associations in patients of diabetes, as well as a proper family history regarding breast cancer which might be already running in their genes. However associations were observed between the GLP-1 analogue use , at two-three years and three to four years; as the rates were more high, but the supporting evidence for this are still lagging. Although it is not possible to rule out its tumor promoting effect on normal breast tissue.

Written By- Dr. Akanksha Singh

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Dr.Akanksha Singh

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