Insulin Glargine and Risk of Cancer: A Meta-Analysis

Abstract

Aims

Recently, more and more attention has been drawn on the long-term effects of insulin glargine. Here we strived to estimate the association of cancer occurrence with the use of insulin glargine.

Methods

We searched all the publications regarding the association between cancer occurrence and the use of insulin glargine using the US National Library of Medicine's PubMed database. Data were independently extracted and analyzed using random or fixed effects meta-analysis depending upon the degree of heterogeneity.

Results

Seven cohort studies were included in the meta-analysis. Cancer occurrence had no significant difference in glargine-treated patients compared to patients treated with other insulins (RR=0.86, 95% CI=0.69–1.07, p=0.17, P_{heterogeneity} <0.00001). In our subgroup analysis, glargine, compared to other insulins, did not increase the risk of breast cancer (RR=1.14, 95% CI=0.65–2.02, p=0.65, P_{heterogeneity}=0.002), prostate cancer (RR=1.00, 95% CI=0.79–1.26, p=0.99, P_{heterogeneity}=0.78), pancreatic cancer (RR=0.57, 95% CI=0.14–2.35, p=0.44, P_{heterogeneity}=0.0002) and gastrointestinal cancer (RR=0.80, heterogeneity 95% CI=0.62–1.02, p=0.07, P_{heterogeneity}=0.86).

Conclusions

This meta-analysis of open-label studies does not support an increased cancer risk in patients treated with insulin glargine. The result provides confidence for the development of insulin glargine, but needs confirmation by further clinical studies.

Keywords

Insulin glargine Cancer Diabetes

References

Mussig

, Staiger

, Kantartzis

, Fritsche

, Kanz

, Haring

H.U.

. Type 2 diabetes mellitus and risk of malignancy: is there a strategy to identify a subphenotype of patients with increased susceptibility to endogenous and exogenous hyperinsulinism? Diabetic Medicine 2011; 28: 276–86.

Dideriksen

L.H.

, Jorgensen

L.N.

, Drejer

. Carcinogenic effect on female rats after 12 months’ administration of the insulin analogue B10 ASP. Diabetes 1992; 41: 143A.

Hemkens

L.G.

, Grouven

, Bender

. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 2009; 52: 1723–44.

Currie

C.J.

, Poole

C.D.

, Gale

E.A.

. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009; 52: 1766–77.

Colhoun

H.M.

. Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia 2009; 52: 1755–65.

Rosenstock

, Fronseca

, McGill

J.B.

. Similar risk of malignancy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: findings from a 5-year randomised, open-label study. Diabetologia 2009; 52: 1971–3.

Zhou

W.B.

, Ding

, Chen

, Liu

X.A.

, Wang

. Toremifene is an effective and safe alternative to tamoxifen in adjuvant endocrine therapy for breast cancer: results of four randomized trials. Breast Cancer Res Treat 2011; 128: 625–31.

Zhou

W.B.

, Xue

D.Q.

, Liu

X.A.

, Ding

, Wang

. The influence of family history and histological stratification on breast cancer risk in women with benign breast disease: a meta-analysis. J Cancer Res Clin Oncol 2011; 137: 1053–60.

Suissa

, Azoulay

, Dell'aniello

, Evans

, Vora

, Pollak

. Long-term effects of insulin glargine on the risk of breast cancer. Diabetologia 2011; 54: 2254–62.

10.

Ljung

, Talback

, Haglund

, Jonasson

J.M.

, Gudbjornsdottir

, Steineck

. Insulin glargine use and short-term incidence of malignancies - a three-year population-based observation. Acta Oncol 2011; 50: 685–93.

11.

Deigaard

, Lynggaard

, Rastam

, Krogsgaard Thomsen

. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia 2009; 52: 2507–12.

12.

Home

P.D.

, Lagarenne

. Combined randomised controlled trial experience of malignancies in studies using insulin glargine. Diabetologia 2009; 52: 2499–506.

13.

Jonasson

J.M.

, Ljung

, Talback

, Haglund

, Gudbjornsdottir

, Steineck

. Insulin glargine use and short-term incidence of malignancies - a population-based follow-up study in Sweden. Diabetologia 2009; 52: 1745–54.

14.

Lee

N.J.

, Norris

S.L.

, Thakurta

. Efficacy and harms of the hypoglycemic agent pramlintide in diabetes mellitus. Ann Fam Med 2010; 8: 542–9.

15.

John

. Basal insulin analogues - a review of data on efficacy and safety. J Assoc Physicians India 2011; 59: 25–8.

16.

Buse

. Insulin glargine (HOE901): first responsibilities: understanding the data and ensuring safety. Diabetes Care 2000; 23: 576–8.

17.

Kuerzel

G.U.

, Shukla

, Scholtz

H.E.

. Biotransformation of insulin glargine after subcutaneous injection in healthy subjects. Curr Med Res Opin 2003; 19: 34–40.

18.

Swinnen

S.G.

, Simon

A.C.

, Holleman

, Hoekstra

J.B.

, Devries

J.H.

. Insulin detemir versus insulin glargine for type 2 diabetes mellitus. Cochrane Database Syst Rev 2011; 6: CD006383.

19.

Rosta

. Diabetes and cancer risk: oncologic considerations. Orv hetil 2011; 152: 1144–55.

20.

Evans

, Shumm-Draeger

P.M.

, Vora

, King

A.B.

. A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations. Diabetes Obes Metab 2011; 13: 677–84.

21.

Staiger

, Hennige

, Staiger

, Haring

H.U.

, Kellerer

. Comparison of the mitogenic potency of regular human insulin and its analogue glargine in normal and transformed human breast epithelial cells. Horm Metab Res 2007; 39: 65–7.

22.

Eckardt

, May

, Koenen

, Eckel

. IGF-1 receptor signalling determines the mitogenic potency of insulin analogues in human smooth muscle cells and fibroblasts. Diabetologia 2007; 50: 2534–43.

23.

Bahr

, Kolter

, Seipke

, Eckel

. Growth promoting and metabolic activity of the human insulin analogue in (HOE 901) in muscle cells. Eur J Pharmacol 1997; 320: 259–65.