The insulin glargine dilemma: an opportunity for the diabetes community?

Stümvoll, Michael; Nawroth, Peter P.

doi:10.1007/s00125-009-1490-9

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…14 , 15 The principal metabolic effects of metformin (i.e., decreased hepatic glucose production and improved insulin sensitivity) target two of the primary metabolic defects contributing to both fasting and postprandial hyperglycemia in patients with T2DM. 14 , 15 , 16 , 17 When used in combination, most oral antihyperglycemic agents do not demonstrate numerically additive reductions in mean hemoglobin A1c (HbA 1c ) values, 18 which likely is a reflection of the positive correlation between baseline glucose concentrations and the magnitude of treatment‐related glucose‐lowering effects. 19 This finding suggests that, if truly additive effects are to be manifested, each drug must contribute greater reductions in HbA 1c relative to monotherapy.…”

mentioning

confidence: 99%

Dipeptidyl Peptidase-4 Inhibitors Administered in Combination With Metformin Result in an Additive Increase in the Plasma Concentration of Active GLP-1

Migoya

Bergeron

Miller

et al. 2010

Clin Pharmacol Ther

161

132

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The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.

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mentioning

confidence: 99%

Dipeptidyl Peptidase-4 Inhibitors Administered in Combination With Metformin Result in an Additive Increase in the Plasma Concentration of Active GLP-1

Migoya

Bergeron

Miller

et al. 2010

Clin Pharmacol Ther

161

132

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“…Hernandez-Diaz et al claimed that current epidemiological evidence is insuffi cient to confi rm or refute a carcinogenic eff ect of explicit insulins in specifi c cancers and supposed further investigation on potential dose eff ect of insulin overall and insulin glargine in particular on colon and BC ( Hernandez-Diaz and Adami, 2010 ). The insulin dilemma on suspicion of promoting cancer on the one hand, stands in contrast to results in terms of oral insulin-sensitizing treat on the other hand ( Stumvoll and Nawroth, 2009 ). Recent in vitro, in vivo and fi rst clinical investigations have shown decreased risk of BC and tumor progression by metformin use.…”

Section: Eff Ects Of Diabetic Treatment On Breast Cancer ▼mentioning

confidence: 99%

Breast Cancer and Diabetes Mellitus

Schott

Schneeweiß

Sohn

2010

Exp Clin Endocrinol Diabetes

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Breast cancer is the leading neoplastic malignancy among females worldwide. Another major health problem in industrial countries is diabetes mellitus type 2, both with a raising tendency. Up to 16% of the elderly breast cancer patients additionally suffer from diabetes. Epidemiologic studies suggest that type 2 diabetes increases breast cancer risk and goes along with an increased mortality however, there has been limited experimental evidence supporting this association. In the present review we summarized epidemiological data on a correlation between diabetes and breast cancer. Further, the diverse hypothesized molecular investigations and purposed mechanisms are recapitulated. The latest discussions on insulin and its enhancement of cancer rates among patients with diabetes have also toughed the breast cancer sector. In contrary, recent data indicate a benefit of breast cancer treatment due to metformin therapy. A large amount of literature is available and provides concepts for future research that is needed to rule out possible overlapping pathomechanism, prognostic factors, therapy interactions as well as possible synergistic or additive or even controversial interaction of chemotherapy and diabetes medication.

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“…In addition serious criticisms have been raised regarding the publication strategy of the Institute for Quality and Efficiency in Health Care. One important lesson to be learned from the glargine dilemma may therefore be to reassess communication and co‐operation between the different stakeholders in diabetes treatment (13).…”

Section: The Influence Of Glucose‐lowering Therapies On Cancer Risk Imentioning

confidence: 99%

New insulins and the risk of cancer

Danne

Bolinder

2010

International Journal of Clinical Practice

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On 26 June 2009, four studies with an accompanying editorial (1) were published online in Diabetologia, the journal of the European Association for the Study of Diabetes (EASD) (2). Performed in Germany, Sweden, England and Scotland using large diabetes and cancer databases, these retrospective epidemiological studies investigated the risk of malignancy in patients treated with insulin analogues, in particular insulin glargine (brand name Lantus), sanofi-aventis). The results have been discussed extensively in the public domain and have led to considerable insecurity of patients treated with insulin analogues. Several position statements and commentaries have been issued (3,4) concluding that a relationship between insulin glargine and cancer cannot be confirmed nor excluded on the basis of currently available data and that the concerns require further in-depth evaluation.

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The insulin glargine dilemma: an opportunity for the diabetes community?

Cited by 6 publications

References 10 publications

Dipeptidyl Peptidase-4 Inhibitors Administered in Combination With Metformin Result in an Additive Increase in the Plasma Concentration of Active GLP-1

Dipeptidyl Peptidase-4 Inhibitors Administered in Combination With Metformin Result in an Additive Increase in the Plasma Concentration of Active GLP-1

Breast Cancer and Diabetes Mellitus

New insulins and the risk of cancer

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