insulin-glargine and Neoplasms

Hyperinsulinemia is a recognized risk factor for cancer and plays a major role for the increased cancer incidence in diabetic patients. Whether insulin analogs, and particularly long-acting analogs, worsen the pro-cancer effect of excess insulin is still controversial.. In this paper we summarize the biological bases for the potential detrimental effect of long-acting analogs on cancer cells and review the in vitro and in vivo evidence on this issue. Because of their different molecular structure relative to native insulin, insulin analogs may activate the insulin receptor (IR) and the post receptor pathways differently. Most, but not all, in vitro evidence indicate that long-acting analogs may have a stronger mitogenic potency than insulin on cancer cells. Notably insulin glargine, the most studied long-acting analog, also has a higher affinity for the insulin-like growth factor (IGF)-1 receptor, a potent growth mediator. In vitro observations, however, may not reflect what occurs in vivo when analogs are metabolized to derivatives with a different mitogenic activity. Clinical studies, mostly retrospective and predominantly concerning glargine, provide contrasting results. The only perspective trial found no cancer increase in patients treated with glargine. All these studies, however, have severe weaknesses because of the insufficient evaluation of important factors such as dose administered, length of exposure, patient follow-up duration and site-specific cancer investigation. Moreover, whether cancer promotion is a long-acting analog class characteristic or a specific effect of a single agent is not clear.. In conclusion the carcinogenic risk of long-acting analogs, and specifically glargine, can be neither confirmed nor excluded. A personalized and shared decision, considering all the individual risk factors (metabolic and non-metabolic), is the suggestion for the clinician.

Topics: Animals; Biomarkers; Blood Glucose; Clinical Decision-Making; Diabetes Mellitus; Humans; Hyperinsulinism; Hypoglycemic Agents; Incidence; Insulin Glargine; Neoplasms; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The main objective of the ORIGIN study was an observation of the effects of treatment with insulin analogue, insulin glargine on cardiovascular complications in patients with severe atherosclerosis and early stages of well-compensated diabetes and prediabetes. The authors expected that a long-term reduction of glycaemia on an empty stomach will reduce the number of occurrences of cardiovascular complications. The study, which was conducted over a period of more than six years, showed neither a positive nor a negative effect of insulin treatment on cardiovascular complications. The second main objective of the study was the following: to compare the effect of the omega-3 fatty acid treatment versus placebo on the development of cardiovascular complications. However, no influence of n-3 fatty acids on the development of cardiovascular complications was found. The study investigated whether the insulin glargine treatment leads to an increased number of cancer occurrences. No correlation between cancer and the insulin glargine treatment was proven in this study. Long-term insulin treatment in the early stages of diabetes led to a minimal increase in weight through the course of six years (1.5 kg) and to three times more hypoglycaemia occurrences compared to placebo. However, the number of hypoglycaemia occurrences was very small.. The study has confirmed the safety of the insulin glargine treatment combined with metformin in the early stages of diabetes, without an increased number of atherosclerosis or cancer occurrences, and with minimal weight gain.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Randomized Controlled Trials as Topic

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Observational Studies as Topic; Risk Factors; Signal Transduction

An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.. To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.. Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):. diabetes patients.. Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.. Any incident cancer.. Cohort and case-control studies.. 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.. Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.. Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

Topics: Breast Neoplasms; Case-Control Studies; Cohort Studies; Colorectal Neoplasms; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Observational Studies as Topic; Publication Bias; Registries; Research Design

The aim of the present paper is to provide some further data on the relationship between β-blocker treatment and the incidence of cancer, using two different approaches (epidemiological study and meta-analysis of clinical trials).. In a consecutive series of 1340 diabetic patients starting insulin therapy, 112 cases of cancer during a mean follow-up of 75.9 months were identified as first hospital admission or death. For each case, the controls were chosen randomly from those members of the cohort matched for age, sex and BMI. The main predefined analysis was the comparison of cases and controls for length of exposure to β-blockers and proportion of patients exposed using a conditional logistic regression which takes into account the matching structure. For the meta-analytic sub-study, an extensive search of Medline and the Cochrane Library (any date up to December 31st, 2011) was performed for all trials in which a β-blocker was used. Mantel-Haenszel Odds Ratios (MH-OR) with 95% confidence intervals for incident malignancies were calculated using a random effect model.. After adjusting for mean daily dose of glargine and metformin, and ischemic heart disease, exposure to β-blockers was associated with a reduced overall risk of cancer (HR 0.33 [0.13; 0.83], p = 0.019; HR for each month of exposure 0.87 [0.77; 0.98], p = 0.025). In the meta-analysis sub-study, performed on nine trials, β-blockers were associated with a non-significant trend toward lower risk of cancer (MH-OR 0.93 [0.86; 1.01], p = 0.070).. Limitations of the observational study are the small sample size that limits the statistical power of analyses, that it was performed on diabetic patients only, and that diagnoses of malignancies were derived from administrative data.. In conclusion, this research seem to confirm a possible beneficial effect of β-blockers against the risk of cancer development.

Topics: Adrenergic beta-Antagonists; Aged; Atenolol; Benzopyrans; Bisoprolol; Carbazoles; Carvedilol; Diabetes Mellitus; Ethanolamines; Female; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Myocardial Ischemia; Nebivolol; Neoplasms; Propanolamines; Risk

Retrospective, observational studies have reported an association between diabetes treatment with insulin and a higher incidence of cancer.. Overview the literature for in vitro and in vivo studies of the metabolic and mitogenic properties of basal insulin analogues and assess the implications for clinical use.. Relevant studies were identified through PubMed and congress abstract database searches; data on metabolic and mitogenic signalling in relation to insulin treatment of diabetes are included in this review.. The balance of evidence shows that although some analogues have demonstrated mitogenic potency in some in vitro studies in cancer cell lines, these findings do not translate to the in vivo setting in animals or to the clinical setting in humans.. The current consensus is that there is no clinical or in vivo evidence to indicate that any commercially available insulin analogue has carcinogenic effects. Large-scale, prospective clinical and observational studies will further establish any potential link.

Topics: Cell Proliferation; Databases, Factual; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Mitogens; Neoplasms; Phosphorylation; Protein Binding; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction

In 2009, several epidemiological studies suggested a higher frequency of malignancy in insulin glargine -treated patients. A number of follow-up epidemiological population studies as well as two randomized, controlled clinical studies, one a 5000-patient retinopathy study and the other a 12,000-patient cardiovascular outcomes trial (ORIGIN), found no higher frequency of malignancy in glargine-treated patients.. We reviewed the existing literature as well as U.S. FDA records to investigate the association of cancer, diabetes, and insulin. There is a 20 - 40% higher incidence of malignancy in type 2 diabetes patients. Certain cancers are more common, including hepatocellular and pancreatic carcinoma, colorectal cancer, renal cancer, and breast and endometrial cancer, and non-Hodgkin's lymphoma. There are numerous inter-related factors which may promote both diabetes and malignancy, including dietary patterns, obesity, insulin resistance, and alcoholism. Patients who receive insulin treatment are typically older and "sicker" than those who receive oral agents.. It is very difficult to prove causal associations between diabetes and cancer due to the host of confounding factors. The hypothesis that hyperinsulinemia and IGF-1 receptor activation promote cancer is strong, but confounded by the association of hyperinsulinemia with obesity, which separately promotes malignancy. Although statistical techniques to adjust for confounding variables can improve epidemiological comparisons, the lesson of the glargine cancer controversy is that controlled clinical trials are the only means to definitely prove hypotheses.

Topics: Animals; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Receptor, IGF Type 1

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.. 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.. 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, 95% CI=0.62-1.02, p=0.07, P(heterogeneity)=0.86).. 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.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Risk

The role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence.. All observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.. A total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence). Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence). Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer.. Results from the meta-analysis don't support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors

To give an overview on the relationship between diabetes mellitus and increased cancer risk.. We identified studies evaluating the association between diabetes mellitus, its treatment with insulin and insulin analogues and malignancies, paying special attention to studies on in vitro and in vivo effects of the long-acting analogue insulin glargine.. Even although the pathophysiological mechanisms underlying the relationship between elevated cancer risk and Type 2 diabetes mellitus are not completely understood, hyperinsulinaemia in the presence of insulin resistance appears to be a key factor. Because of the mitogenic actions of insulin at high concentrations, hyperinsulinaemia may favour tumorigenesis. In line with this, an insulin-based therapy is associated with an increased cancer risk, whereas an insulin-sensitizing treatment results in a cancer risk reduction. Furthermore, alterations of the insulin receptor profile on tumour cells may contribute to an enhanced susceptibility towards insulin. Studies on the analogue insulin glargine have been controversial. In vitro data pointed to an elevated mitogenicity of insulin glargine, whereas in vivo data did not confirm cancerogenous effects. Moreover, recently published clinical studies on the association of insulin glargine (Lantus®) and cancer suggest that treatment with insulin glargine is not associated with increased cancer risk.. The relationship between elevated cancer risk and Type 2 diabetes mellitus has been shown by numerous epidemiological studies, with endogenous and exogenous hyperinsulinaemia in the presence of insulin resistance as potential underlying pathophysiological mechanisms. Recent clinical studies do not support an increased cancer risk in patients treated with insulin glargine.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Neoplasms; Risk Factors

Type 2 diabetes mellitus and malignant tumors are frequent diseases worldwide. The incidence of these two diseases is growing continuously and causes serious health care problem. Population based epidemiologic studies show that the coexistence of type 2 diabetes and malignant tumors is more frequent than expected by the age-corrected incidence and prevalence of each disease. Epidemiologic studies and meta-analyses show that type 2 diabetes increases the risk and tumor specific mortality of certain cancers. The overlapping risk factors of the diseases suggest a relationship between type 2 diabetes and malignant tumors, with a significant role of obesity as a major risk factor. In the pathophysiology of type 2 diabetes there are several biological processes, which may explain the higher cancer risk in type 2 diabetes. In vitro experiments, and in vivo animal studies show that the mitotic effect of hyperinsulinemia plays an important role in the relationship of cancer and type 2 diabetes mellitus. Recent studies show that the different treatment modalities, antidiabetic drugs and their combinations used for the treatment of type 2 diabetes can modify cancer risk. The majority of the data show that metformin therapy decreases, while insulin secretagog drugs slightly increase the risk of certain types of cancers in type 2 diabetes. Metformin can decrease cell proliferation and induce apoptosis in certain cancer cell lines. Endogenous and exogenous (therapy induced) hyperinsulinemia may be mitogenic and may increase the risk of cancer in type 2 diabetes. Human studies showed that the analogue insulin glargin increases the risk of certain cancers. As a result of conceptual weaknesses in study design, data collection, and statistical methods the results of these studies are questionable. According to present knowledge, obtaining and maintaining optimal metabolic target values with the appropriate choice of treatment modality is the aim of treatment in type 2 diabetes. Presently, study results showing elevated mitogenic potential with some antidiabetic treatment modalities are not taken into account, when considering the choice of antidiabetic treatment in type 2 diabetic patients. In the care of patients with increased cancer risk, oncologic considerations should be taken into account. Well designed, prospective, clinical studies would be necessary to demonstrate the possible correlation between treatment modalities of type 2 diabetes and change of cancer risk in

Topics: Adipokines; Age Factors; Animals; Cytokines; Diabetes Complications; Diabetes Mellitus, Type 2; Feeding Behavior; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Metformin; Motor Activity; Neoplasms; Obesity; Prevalence; Research Design; Risk Factors; Sex Factors; Smoking; Sulfonylurea Compounds; Thiazolidinediones

Although diabetes has been known to increase the risk of cancer for over a century, it was not until recently when this area gained momentum and generated a lot of interest. That is in- part because of the rising global diabetes epidemic and the wide spread use of insulin analogues, metformin and other anti-diabetic agents, providing hypothesis generating data on the cancer risk in the diabetic population. Type 2 diabetes is associated with increased risk of breast, colon, pancreatic and other types of cancer, while type 1 diabetes is associated with increase in stomach, pancreatic, endometrial and cervical cancer. Mechanisms postulated for increased cancer risk in diabetes include hyperglycemia, hyperinsulinemia with stimulation of IGF-1 axis, obesity that serves as a common soil hypothesis for both cancer and diabetes as well as other factors such as increased cytokine production. More recently some antidiabetic agents have been thought to increase cancer risk such as insulin glargine, while metformin appears to lower cancer risk. In this review, we present the evidence for the link between diabetes and cancer highlighting the general mechanisms proposed for such a link as well as specific hypotheses for individual cancer. We will also discuss the role of insulin, metformin and other antidiabetic agents in cancer risk.

Topics: Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Insulins; Metformin; Neoplasms; Risk Assessment; Risk Factors

Numerous epidemiological studies have demonstrated an association between increased risk of cancer development and progression and type 2 diabetes mellitus as well as obesity. The underlying mechanisms remain elusive, but hyperinsulinaemia in the presence of insulin resistance appears to be an important factor. Hyperinsulinaemia may favour tumorigenesis, as insulin has not only metabolic actions, but is also mitogenic at high concentrations. Besides, susceptibility of tumour cells against insulin may be increased due to changes in the insulin receptor profile. A diabetes therapy with insulin or sulfonylureas, which leads to elevated exogenous or endogenous insulin levels, appears to be related with an increased cancer risk, whereas administration of metformin or thiazolidinediones, which is associated with a decrease of insulin concentrations, results in risk reduction. However, in light of the numerous epidemiological studies showing an association between increased cancer risk and reduced physical activity one cannot exclude that hyperinsulinaemia in the presence of insulin resistance is only a surrogate parameter of reduced physical activity. In the past years, several insulin analogues have been developed which may have altered mitogenic actions compared to human insulin due to their structural changes. For the long-acting analogue insulin glargine, in vitro data, though controversial, pointed to an increased mitogenicity that was, however, not confirmed by in vivo studies. Recently, six clinical studies have been published that analysed the association between the application of insulin glargine (Lantus) and cancer development. The current clinical data do not allow the conclusion that treatment with insulin glargine is associated with increased cancer risk. On the other hand, prospective studies that exclude an impact on cancer risk in risk populations are currently not available. Future studies are required to investigate whether a subpopulation characterised by a less rapid metabolization of insulin glargine in vivo may be at increased cancer risk. In the present article, we give an overview on the association between diabetes mellitus, its treatment with insulin analogues, and cancer.

Topics: Diabetes Mellitus, Type 2; Exercise; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Mutagenicity Tests; Neoplasms; Obesity; Risk Factors

Diabetes mellitus is a chronic disease that affects > 23.6 million Americans, and occurs when the body is unable to produce or becomes resistant to endogenous insulin. This alteration of insulin's action reduces adequate utilization of glucose transporter type 4 (GLUT4) receptors, which are responsible for cellular glucose uptake. Thus, exogenous administration of human insulin and insulin analogs is an important modality used to reduce morbidity and mortality in both type 1 and type 2 diabetes. According to 2007 estimates, 27% of all patients with diabetes use some form of insulin therapy. The increasing utilization of insulin has become a cause for concern because findings from several observational trials have suggested an association with an increased risk of developing cancer. To help elucidate the potential interplay between insulin use and cancer, we searched PubMed and MEDLINE to identify articles that assessed the carcinogenic and/or mitogenic potential of diabetes treatments, focusing on insulin specifically. Data from our review suggest that insulin analogs, particularly insulin glargine, may play more of a mitogenic than a carcinogenic role in association with different types of cancer, suggesting an amplified rate of existing tumor growth in the presence of insulin analogs. Evidence for insulin-induced mitogenicity appears to be most prevalent in prostate, breast, pancreatic, and colorectal cancers. In conclusion, the positive effects of insulin therapy on reducing morbidity and mortality in diabetes greatly outweigh the risks at this time. However, clinicians must be diligent in both screening for new cancers in patients receiving insulin and in monitoring for tumor growth or maintenance of remission in patients with existing cancers.

Topics: Cell Line, Tumor; Cell Transformation, Neoplastic; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Product Surveillance, Postmarketing; Receptors, Somatomedin

The widespread use of insulin analogues is based not only on the pharmacokinetics of these preparations, which is much closer to the physiology of insulin secretion under normal conditions, but also on their safety and effectiveness. The publication of a possible association between the use of a long-acting insulin analogue (glargine) and breast cancer has caused uneasiness among the medical community regarding the safety of these analogues. The mechanism of increased tumor activity of insulin analogues is explained by the fact that they act through insulin receptors (IR) and insulin-like growth factor-1 (IGF-1R), stimulating cell growth and inhibiting apoptosis. There are two major mechanisms: an increase in the binding time of insulin to IR and increased activation of IGF-1R. Therefore, to evaluate the safety of an analogue, the slower dissociation rate from its insulin receptor must be excluded, as well as the increased affinity for the IGF-1 receptor. This is equivalent to an index of mitogenic/metabolic activity of less than 1. These aspects can only be evaluated through study of cell lines and animal testing, which are reductionist models that cannot always be extrapolated to humans. To date, there are no data to question the safety of insulin analogues in general. However, the results of observational studies and some in vitro studies, suggesting a potential risk of mitogenicity with the administration of glargine, have caused some alarm among the medical community. Until now, there are no data to refute or confirm this risk and, therefore, evaluation of the existing data is crucial to obtain objective information.

Topics: Amino Acid Sequence; Animals; Apoptosis; Cell Line, Tumor; Cell Transformation, Neoplastic; Diabetes Mellitus; Drug Evaluation, Preclinical; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Male; Mammary Neoplasms, Experimental; Mitosis; Molecular Sequence Data; Neoplasms; Rats; Rats, Sprague-Dawley; Receptor, IGF Type 1; Receptor, Insulin

Type 2 diabetes mellitus has been associated with an increased risk of hepatic, pancreatic, colon, endometrial, breast, and bladder cancer. Although a mechanism of action for the increased risk has been postulated, no definitive evidence has been completely elucidated in the medical literature. Results of recently released studies documented the use of specific antidiabetic drugs with increased rates of cancer. The insulin analog glargine was the focus of four observational studies published in 2009 that outlined an increase in the rates of cancer associated with its use. In contrast, the use of metformin has been shown to possibly decrease the rate of specific cancers when used in the treatment of type 2 diabetes. These data regarding cancer risk and antidiabetic drugs are contradictory and at this time are inconclusive. Until results of long-term randomized prospective studies are available to elucidate a correlation with cancer and insulin, we must continue treating diabetes in order to avert the long-term complications of the disease.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Metformin; Neoplasms; Risk

The risk of malignancy in patients using insulin glargine was evaluated.. Patients with diabetes mellitus have increased rates of cancers including breast, colon, and pancreatic cancers. Since nondiabetic patients with increased levels of insulin have similar rates of the same cancers, hyperinsulinemia could be key. Normally, insulin produces metabolic effects and insulin-like growth factor-I (IGF-I) produces mitogenic effects. Since the molecules are structurally similar, it is possible for insulin to act like IGF-I, promoting mitogenicity. Concern that insulin may promote the growth of some cancers is heightened with insulin analogues, since changing the structure of human insulin could produce molecules with increased mitogenic potential. In vivo, insulin glargine has been shown to have greater mitogenic potential than human insulin. It is unknown whether this occurs in vitro, because the insulin glargine molecule is transformed once injected. Studies published in 2009 suggest that patients on insulin glargine could be at greater risk for cancer than patients on other antidiabetes therapies, but the trial results are conflicting. In response, the Food and Drug Administration, American Diabetes Association, American Association of Clinical Endocrinologists, and European Association for the Study of Diabetes have formally stated that patients should continue to use insulin glargine until more information is available.. Studies on the relationship between insulin glargine and cancer have been inconclusive.

Topics: Animals; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Mitogens; Neoplasms; Risk

In youth with type 1 diabetes (T1D), high haemoglobin A1c (HbA1c) levels are associated with an increased risk for diabetic ketoacidosis (DKA).. This study examined whether daily school-supervised basal insulin injections were feasible and if they reduced the risk of morning ketosis in children and adolescents with high HbA1c levels. We hypothesized that supervised glargine and degludec would reduce the risk of ketosis and that the prolonged action of degludec would protect from ketosis after consecutive days of unsupervised injections.. After a 2-4-week run-in, youth (10-18 years, HbA1c ≥ 8.5%) managing T1D with injections were randomized to school-supervised administration of degludec or glargine for 4 months. School nurses observed daily blood β-hydroxybutyrate (BHB) and glucose checks. During COVID closures, the research team supervised procedures remotely.. Data from 28 youth (age 14.3 ± 2.3 years, HbA1c 11.4 ± 1.9%, 64% F) were analysed. School-supervised injections of both basal insulins for 1-4 days progressively lowered the percent of participants with elevated BHB. The percent of participants with elevated BHB (≥0.6 mmol/L) after 2 days of unsupervised basal insulin doses at home was greater in the glargine than degludec group but had a high p-value (17.2% vs. 9.0%, p = 0.3). HbA1c was unchanged in both groups.. In youth with T1D at high risk for DKA, daily supervised long-acting insulin administration decreased the probability of elevated ketone levels on subsequent school days, regardless of basal insulin type. A larger sample size may have demonstrated that the longer action profile of degludec would offer additional protection from ketosis during days of not attending school.. Engaging school-based caregivers in management of youth with T1D on injected insulin may decrease clinically significant ketosis and minimize acute complications of diabetes.

Topics: Adolescent; Blood Glucose; Child; COVID-19; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Neoplasms; Pilot Projects

OBJECTIVE Epidemiologic studies linking insulin glargine and glucose-lowering therapies to cancers and n-3 fatty acids to cancer prevention have not been confirmed. We aimed to assess the effect of insulin glargine and n-3 fatty acids on incident cancers within the context of the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial. RESEARCH DESIGN AND METHODS The ORIGIN trial is an international, long-term, randomized two-by-two factorial study comparing insulin glargine with standard care and n-3 fatty acids with placebo (double blind) in people with dysglycemia at high risk for cardiovascular events. The primary outcome measure (cancer substudy) was the occurrence of any new or recurrent adjudicated cancer. Cancer mortality and cancer subtypes were also analyzed. RESULTS Among 12,537 people (mean age 63.5 years, SD 7.8; 4,388 females), 953 developed a cancer event during the median follow-up of 6.2 years. In the glargine and standard care groups, the incidence of cancers was 1.32 and 1.32 per 100 person-years, respectively (P = 0.97), and in the n-3 fatty acid and placebo groups, it was 1.28 and 1.36 per 100 person-years, respectively (P = 0.39). No difference in the effect of either intervention was noted within predefined subgroups (P for all interactions ≥0.17). Cancer-related mortality and cancer-specific outcomes also did not differ between groups. Postrandomization HbA1c levels, glucose-lowering therapies (including metformin), and BMI did not affect cancer outcomes. CONCLUSIONS Insulin glargine and n-3 fatty acids have a neutral association with overall and cancer-specific outcomes, including cancer-specific mortality. Exposure to glucose-lowering therapies, including metformin, and HbA1c level during the study did not alter cancer risk.

Topics: Antineoplastic Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Omega-3; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Metformin; Middle Aged; Neoplasms

The aim of the present paper is to provide some further data on the relationship between β-blocker treatment and the incidence of cancer, using two different approaches (epidemiological study and meta-analysis of clinical trials).. In a consecutive series of 1340 diabetic patients starting insulin therapy, 112 cases of cancer during a mean follow-up of 75.9 months were identified as first hospital admission or death. For each case, the controls were chosen randomly from those members of the cohort matched for age, sex and BMI. The main predefined analysis was the comparison of cases and controls for length of exposure to β-blockers and proportion of patients exposed using a conditional logistic regression which takes into account the matching structure. For the meta-analytic sub-study, an extensive search of Medline and the Cochrane Library (any date up to December 31st, 2011) was performed for all trials in which a β-blocker was used. Mantel-Haenszel Odds Ratios (MH-OR) with 95% confidence intervals for incident malignancies were calculated using a random effect model.. After adjusting for mean daily dose of glargine and metformin, and ischemic heart disease, exposure to β-blockers was associated with a reduced overall risk of cancer (HR 0.33 [0.13; 0.83], p = 0.019; HR for each month of exposure 0.87 [0.77; 0.98], p = 0.025). In the meta-analysis sub-study, performed on nine trials, β-blockers were associated with a non-significant trend toward lower risk of cancer (MH-OR 0.93 [0.86; 1.01], p = 0.070).. Limitations of the observational study are the small sample size that limits the statistical power of analyses, that it was performed on diabetic patients only, and that diagnoses of malignancies were derived from administrative data.. In conclusion, this research seem to confirm a possible beneficial effect of β-blockers against the risk of cancer development.

Topics: Adrenergic beta-Antagonists; Aged; Atenolol; Benzopyrans; Bisoprolol; Carbazoles; Carvedilol; Diabetes Mellitus; Ethanolamines; Female; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Myocardial Ischemia; Nebivolol; Neoplasms; Propanolamines; Risk

To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT).. Fifty inpatients were prospectively randomized to receive sliding-scale regular insulin (SSRI) alone (n = 25) or in combination with insulin glargine (n = 25). NPH insulin was added for persistent hyperglycemia in the SSRI group (glucose >10 mmol/l).. Glycemic control was similar in the SSRI and glargine groups (mean +/- SD study glucose 8.9 +/- 1.6 vs. 9.2 +/- 1.6 mmol/l, respectively; P = 0.71). NPH insulin was added in 48% of the SSRI group subjects. There were no group differences in frequency of hypoglycemia (1.3 +/- 4.1 vs. 1.1 +/- 1.8%; P = 0.35), total adverse events, or length of stay.. Both insulin strategies (SSRI with the addition of NPH for persistent hyperglycemia and glargine) demonstrated similar efficacy and safety in non-critically ill hospitalized patients with type 2 diabetes during ENT.

Topics: Aged; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Severity of Illness Index

Topics: Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Neoplasms; Risk Factors

The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies.. National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin.. A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences.. The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Neoplasms; Regression Analysis; Young Adult

Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.. To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.. 23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years).. 2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.. In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Female; Finland; Gastrointestinal Diseases; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Risk

Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years.. From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36-1.19).. Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data.

Topics: Diabetes Mellitus; Disease-Free Survival; Electronic Health Records; Female; Humans; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Time Factors

To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer.. We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality.. More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95-1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses.. Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged; Neoplasms; Probability; Proportional Hazards Models; Registries; Risk Factors

To explore in France the relationship between insulin glargine use and overall and specific cancer risks in type 2 diabetic patients compared with other basal insulins.. Data were extracted from French health insurance information system (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked with data from the French Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). Included were 70,027 patients aged 40-79 years who started a basal insulin in 2007-2009. Cox proportional hazards models with age as time-scale were used to calculate multivariate-adjusted hazard ratios for associations between type of basal insulin and risk of overall cancer, breast cancer, and seven other cancer sites.. The median follow-up was 2.67 years in patients exposed to insulin glargine. Absolute event rates for all cancer in patients exposed to glargine versus other basal insulin users were 1,622 and 1,643 per 100,000 person-years, respectively. No significant association was observed between glargine exposure and overall cancer incidence after adjustment for sex, with a hazard ratio of 0.97 (95% CI 0.87-1.07), or after additional adjustment for any other hypoglycemic agent use and duration of diabetes. No increased risk of breast cancer was observed for glargine users compared with other basal insulins users, with a fully adjusted hazard ratio of 1.08 (0.72-1.62).. In a large cohort of patients newly treated by basal insulin, no increased risk of any cancer was observed in insulin glargine users compared with other basal insulin users. Because follow-up did not exceed 4 years, longer-term studies are needed.

Topics: Adult; Aged; Databases, Factual; Female; France; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasms

Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study.. Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes.. Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified.. Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin.

Topics: Breast Neoplasms; Cohort Studies; Community Pharmacy Services; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Electronic Health Records; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Insulin, Regular, Human; Male; Medical Record Linkage; Middle Aged; Neoplasms; Netherlands; Patient Admission; Proportional Hazards Models; Risk

A number of observational studies have linked insulin glargine (A21Gly,B31Arg,B32Arg human insulin) with a putative increased cancer risk, particularly breast cancer, but many of these 'first generation' studies had study design and analysis flaws, and were inconclusive. A small number of 'second generation' studies are now emerging in which the applied pharmaco-epidemiological principles are more robust. For example, when Ruitar and colleagues (Diabetologia DOI: 10.1007/s00125-011-2312-4 ) focused specifically on breast cancer rather than all incident cancer risk, they were able to show a positive association with insulin glargine for breast cancer although there was no association with all incident cancer risk. A list of preferred qualities for pharmaco-epidemiological studies is presented.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Insulin, Regular, Human; Male; Neoplasms

Recent studies suggesting an increased cancer risk with glucose-lowering agents have received widespread publicity. The objectives of this study were to evaluate the comparability in underlying cancer risk and patterns of cancer risk over time with different glucose-lowering agents.. The General Practice Research Database (GPRD) was used to identify cohorts of new users. Cancer outcomes were obtained from the GPRD, Hospital Episode Statistics and cancer registries. Relative rates of cancer comparing different glucose-lowering agents were estimated using Poisson regression.. A total of 206,940 patients was identified. There was no difference in cancer risk and quartile for HbA(1c) value. There were differences in cancer incidence in the first 6 months after starting treatment (adjusted relative rate of 0.83 [95% CI 0.70, 0.99] with thiazolidinediones, 1.34 [95% CI 1.19, 1.51] with sulfonylureas and 1.79 [95% CI 1.53, 2.10] with insulin, compared with metformin). Insulin users had decreasing cancer incidence over time (adjusted relative rate of 0.58 [95% CI 0.50, 0.68] during months 6-24, relative rate of 0.50 [95% CI 0.42, 0.59] during months 25-60 and relative rate of 0.48 [95% CI 0.40, 0.59] during months 60+) compared with months 0-6 after starting insulin. Similar patterns were found with sulfonylureas and metformin. There were no increases over time with insulin glargine (A21Gly, B31Arg, B32Arg human insulin; relative rate of 0.70 [95% CI 0.52, 0.95], 0.77 [95% CI 0.56, 1.07] and 0.60 [95% CI 0.36, 1.02], respectively, for 6-24, 25-60 and >60 months).. These findings do not provide evidence of either beneficial or adverse effects of glucose-lowering agents on cancer risk and are consistent with changes in diabetes treatment in the few months prior to the diagnosis of cancer.

Topics: Aged; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Follow-Up Studies; General Practice; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Poisson Distribution; Registries; Sulfonylurea Compounds; Thiazolidinediones; United Kingdom

Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010.. We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin, and adjusted for insulin, biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant (≥ 80% use time) users of insulin glargine compared with equivalent human insulin users.. Only type 2 diabetic patients were studied. Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin, respectively, to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin, respectively. All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 (95% CI 0.28, 1.25) in incident exclusive users to 0.58 (95% CI 0.34, 1.01) in all predominant users. Cancer risk increased with exposure to insulin or sulfonylureas in these patients. Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 (95% CI 0.32, 1.06) to 0.56 (95% CI 0.36, 0.87).. There was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone. The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin, thereby excluding a competitive risk bias.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Female; France; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Mortality; National Health Programs; Neoplasms; Risk; Sulfonylurea Compounds; Young Adult

Topics: Angiotensin Receptor Antagonists; Animals; Biomedical Research; Causality; Clopidogrel; Cyclooxygenase 2 Inhibitors; Humans; Incidence; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Rosiglitazone; Thiazolidinediones; Ticlopidine

Metformin is associated with reduced cancer-related morbidity and mortality. The aim of this study was to assess the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients.. A nested case-control study was performed in a cohort of 1,340 patients by sampling, for each case subject, age-, sex-, and BMI-matched control subjects from the same cohort.. During a median follow-up of 75.9 months, 112 case patients who developed incident cancer and were compared with 370 control subjects. A significantly lower proportion of case subjects were exposed to metformin and sulfonylureas. After adjustment for comorbidity, glargine, and total insulin doses, exposure to metformin, but not to sulfonylureas, was associated with reduced incidence of cancer (odds ratio 0.46 [95% CI 0.25-0.85], P = 0.014 and 0.75 [0.39-1.45], P = 0.40, respectively).. The reduction of cancer risk could be a further relevant reason for maintaining use of metformin in insulin-treated patients.

Topics: Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Neoplasms; Sulfonylurea Compounds

To further investigate the association of cancer occurrence with the use of insulin glargine.. We followed 114 838 individuals using insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2008, we noted the occurrence of malignancies (cohort I). Insulin users between 1 July and 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 (cohort II). Users of insulin during three consecutive six-month periods from 1 July 2005 to 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 (cohort III). The Prescribed Drug Register, the Cancer Register, and the Causes of Death Register were used to obtain information on targeted person-time and outcome. We retrieved variables reflecting potential confounding factors from the Swedish National Diabetes Register, the Prescribed Drug Register, the Patient Register, the Medical Birth Register and the National Education Register. With Poisson regression we evaluated the association between insulin use and malignancy outcome with adjustment for confounders.. The adjusted incidence rate ratio (and 95% confidence interval) for women who used insulin glargine alone compared with those who used other types of insulin, was 1.60 (1.10-2.32) for breast cancer but included 1.0 for malignancy outcomes other than breast cancer for men and women when analyzing cohort I with follow-up in 2006-2008. For cohort II and III the corresponding incidence rate ratios were 1.38 (0.87-2.18), and 0.87 (0.41-1.85), respectively.. We do not see an increased risk during 2008 for breast cancer in the insulin glargine group. We need data for additional years before we can state with reasonable certainty that the increase in breast cancer incidence that we observed in Sweden in 2006 and 2007 was due to a random fluctuation or whether there is an association with the use of insulin glargine.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Cohort Studies; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Observation; Population; Registries; Risk Factors; Time Factors

Preclinical and observational studies raise the concern about the safety of insulin glargine in terms of cancer initiation and promotion. This study is designed to examine cancer incidence associated with use of insulin glargine vs. intermediate/long-acting human insulin (HI).. A retrospective cohort study using the Taiwan National Health Insurance claims database was conducted to identify adult patients with type 2 diabetes mellitus and without a history of cancer who initiated insulin glargine (n = 10,190) or intermediate/long-acting HI (n = 49,253) during 2004-2007. Exclusive users were followed from the date of insulin initiation to the earliest of cancer diagnosis, death, disenrollment, or December 31 2007. We estimated adjusted hazard ratios and 95% confidence intervals (CIs) with Cox proportional hazards models adjusting for baseline propensity score.. The incidence rate of all cancer per 1,000 person-years was 13.8 for insulin glargine initiators (179 cases) and 16.0 for intermediate/long-acting HI initiators (1,445 cases) during an average follow-up of 2 years. No significant difference in overall cancer risk between insulin glargine initiators and HI initiators was found. For men, however, the adjusted hazard ratio of insulin glargine use as compared with intermediate/long-acting HI was 2.15 (95% CI 1.01-4.59) for pancreatic cancer, and 2.42 (95% CI 1.50-8.40) for prostate cancer. The increased risk was not observed among women.. Insulin glargine use did not increase the risk of overall cancer incidence as compared with HI. The positive associations with pancreatic and prostate cancer need further evaluation and validation.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms; Retrospective Studies

In vitro evidence suggests insulin glargine promotes tumors; observational human studies are conflicting. We aimed to expand understanding of this potential treatment risk.. This retrospective cohort study of type 2 diabetic patients >68 years old used Medicare inpatient, outpatient (2003-2008), and prescription data (2006-2008). Adjusting for patient characteristics, dose, and metformin use, Cox models yielded hazard ratios (HRs) for incident cancer (breast, prostate, pancreas, colon, any site) associated with three forms of insulin: nonglargine, glargine, or glargine plus nonglargine (combination).. Overall, 81,681 patients were followed for a mean of 23.1 months. Mean age was 77.4 years. Treatment group distribution was 20.7% glargine, 60.5% nonglargine, 18.7% combination insulin. We observed 5,466 incident cancers; crude rates did not vary by treatment group. In fully adjusted models, nonglargine use was the referent; glargine was not associated with significant increased risk of any cancer measure. In secondary analyses including only the top quartile of daily insulin dose patients, glargine was not associated with any cancer risk difference; combination insulin was associated with higher breast cancer risk (HR 1.75 [95% CI 1.10-2.78]) and lower colon cancer risk (0.33 [0.13-0.80]). In age-stratified analyses of highest-dose users, combination insulin conferred a higher risk of breast cancer in those ≤75 years old (2.87 [1.45-1.59]).. The general lack of association between glargine-only use and cancer is reassuring. Breast cancer risk associated with high-dose combination insulin in secondary analyses could result from multiple comparisons, residual confounding, or true association; further research is warranted.

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Diabetes Mellitus, Type 2; Female; Humans; Insulin Glargine; Insulin, Long-Acting; Male; Neoplasms; Retrospective Studies

Topics: Cohort Studies; Confounding Factors, Epidemiologic; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Neoplasms; Risk Factors; Safety

Either endogenous or exogenous hyperinsulinaemia in the setting of insulin resistance promotes phosphorylation and activation of farnesyltransferase, a ubiquitous enzyme that farnesylates Ras proteins. Increased availability of farnesylated Ras at the plasma membrane enhances mitogenic responsiveness of cells to various growth factors, thus contributing to progression of cancer and atherosclerosis. This effect is specific to insulin, but is not related to the type of insulin used. The stimulatory effect of hyperinsulinaemia on farnesyltransferase in the presence of insulin resistance represents one potential mechanism responsible for mitogenicity and atherogenicity of insulin.

Topics: Atherosclerosis; Cell Division; Diabetes Mellitus; Farnesyltranstransferase; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Neoplasms; ras Proteins

Topics: Diabetes Mellitus; Dose-Response Relationship, Drug; Ethics, Medical; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk Factors; Safety

Topics: Conflict of Interest; Drug Industry; Ethics, Pharmacy; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms

Topics: Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Safety

Topics: Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Registries; Reproducibility of Results; Risk Factors

Recent epidemiological studies suggested that some insulin analogues could be associated with increased risk of cancer. The present study is aimed at assessing the long-term association of different insulin analogues with cancer incidence.. A nested case-control study dataset was generated from the cohort study dataset (n = 1,340 insulin-treated diabetic outpatients) by sampling control subjects from the risk sets. For each case subject, the control subjects (up to five) were chosen randomly from those members of the cohort who are at risk for the same follow-up time of the case subject. Five-year age classes, sex, and BMI classes (<18.5, 18.5-24.9, 25-29.9, and >or=30 kg/m(2)) were considered as additional categorical matching variables.. During a median follow-up of 75.9 months (interquartile range 27.4-133.7), 112 case subjects of incident cancer were compared with 370 matched control subjects. A significantly higher mean daily dose of glargine was observed in case subjects than in control subjects (0.24 IU/kg/day [0.10-0.39] versus 0.16 IU/kg/day [0.12-0.24], P = 0.036). Incident cancer was associated with a dose of glargine >or=0.3 IU/kg/day even after adjusting for Charlson comorbidity score, other types of insulin administration, and metformin exposure (odds ratio 5.43 [95% CI 2.18-13.53], P < 0.001). No association between incident cancer and insulin doses was found for human insulin or other analogues.. The possibility of association between cancer and higher glargine doses suggests that dosages should always be considered when assessing the possible association of insulin and its analogues with cancer.

Topics: Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasms

Several insulin analogues have been developed in recent years and are increasingly being used in the treatment of diabetes. However, modifying the insulin molecule not only changes its metabolic effects, but can also alter its mitogenic potency. In vitro experiments had previously suggested a potential association between insulin analogues and cancer. In 2009 several articles were published in Diabetologia describing an association between administration of glargine (Lantus) and higher incidence of cancer rates. The present article aims at briefly presenting the state of the art based upon currently available data on insulin and cancer. We will summarize the mechanisms by which insulin can increase cell proliferation, the observations reported in recent publications and finally conclude with some practical recommendations.

Topics: Diabetes Mellitus; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk

Diabetes mellitus has reached epidemic proportions worldwide, eliciting extensive research on both the disease process and its treatment. Regardless of diabetes type, the progressive nature of the disease makes insulin the long-term mainstay of diabetes management. Recently, the insulin analog glargine was reported in several epidemiologic studies to be associated with an increased risk of cancer. Inconsistent study results and media attention have caused much angst and concern to health care professionals and the general population. A clear understanding of the current evidence is needed to adequately develop a patient-oriented risk:benefit assessment. Members of the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy evaluated available evidence to provide guidance and discussion on the risk of cancer with insulin glargine use. We believe the current link between insulin glargine and cancer is tenuous but merits further evaluation. An independent analysis of all available glargine clinical trial data should be performed, and a vigorous postmarketing safety study of glargine should be conducted. Until more substantial data are available, however, neither the choice of initial insulin therapy nor insulin maintenance regimens should be influenced by the current information linking insulin glargine to cancer.

Topics: Clinical Trials as Topic; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Meta-Analysis as Topic; Neoplasms; Risk Factors; Societies, Pharmaceutical; United States

Insulin glargine was the first long-acting human insulin analogue to be authorised in the European Union, in the early 2000s, for the treatment of diabetes mellitus. It has about a 6-fold increase in affinity for the insulinlike growth factor 1 (EGF-1) receptor compared with natural human insulin, which may stimulate tumour development. Four European epidemiological studies published in 2009 examined the risk of cancer in diabetic patients treated with insulin glargine. One of these studies, conducted in Germany, showed a statistically significant dose-dependent increase in the risk of cancer. Two other studies, one in Scotland and the other in Sweden, showed an increase in the risk of breast cancer. The fourth study, conducted in the UK, showed a lower risk of cancer in patients on metformin. This evidence is inconclusive, notably because these studies did not take confounding factors into account. Nevertheless, the results tend to be similar and consistent with certain pharmacological mechanisms. In practice, pending more solid evidence, these epidemiological results should be taken into account when weighing the risk-benefit balance of insulin therapy for diabetic patients, on a case by case basis, depending on the type of diabetes, patient history, life expectancy, and the possible practical advantages of insulin glargine.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms

Topics: Animals; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Neoplasms; Obesity; Receptor, IGF Type 1; Receptor, Insulin; Risk

The aim of this cohort study was to investigate the risk of malignant neoplasms and mortality in patients with diabetes treated either with human insulin or with one of three insulin analogues.. Data were provided by the largest German statutory health insurance fund (time-frame: January 1998 to June 2005 inclusive), on patients without known malignant disease who had received first-time therapy for diabetes mellitus exclusively with human insulin, aspart, lispro or glargine. The primary outcome was the diagnosis of a malignant neoplasm. Data were analysed by multiple Cox regression models adjusting for potential confounders.. A total of 127,031 patients were included, with a mean follow-up time of 1.63 (median 1.41, maximum 4.41) years. A positive association between cancer incidence and insulin dose was found for all insulin types. Because patients receiving combined therapy with insulin analogues and human insulin were excluded, the mean daily dose was much lower for glargine than for human insulin, and a slightly lower cancer incidence in the glargine group was found. After adjusting for dose, a dose-dependent increase in cancer risk was found for treatment with glargine compared with human insulin (p < 0.0001): the adjusted HR was 1.09 (95% CI 1.00 to 1.19) for a daily dose of 10 IU, 1.19 (95% CI 1.10 to 1.30) for a daily dose of 30 IU, and 1.31 (95% CI 1.20 to 1.42) for a daily dose of 50 IU. No increased risk was found for aspart (p = 0.30) or lispro (p = 0.96) compared with human insulin.. Considering the overall relationship between insulin dose and cancer, and the lower dose with glargine, the cancer incidence with glargine was higher than expected compared with human insulin. Our results based on observational data support safety concerns surrounding the mitogenic properties of glargine in diabetic patients. Prospective long-term studies are needed to further evaluate the safety of insulin analogues, especially glargine.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Cohort Studies; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Patient Selection; Proportional Hazards Models; Regression Analysis; Reproducibility of Results

Topics: Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk Factors

In the light of a report suggesting that insulin glargine may increase cancer occurrence, the EASD asked us to perform this study.. We followed 114,841 individuals who had a prescription dispensed for insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2007, we noted the occurrence of malignancies. Seven different nationwide registers were used to obtain information on insulin exposure, outcome and possible confounders; these were linked using the unique personal identity number assigned to every Swedish resident.. After adjustment for age and, when appropriate, sex, users of insulin glargine alone (no other types of insulin), compared with users of types of insulin other than insulin glargine, had an RR of 1.99 (95% CI 1.31-3.03) for breast cancer, 0.93 (95% CI 0.61-1.40) for gastrointestinal cancer, 1.27 (95% CI 0.89-1.82) for prostate cancer and 1.07 (95% CI 0.91-1.27) for any type of malignancy. Adjustment for age, smoking, BMI, age at onset of diabetes, age at birth of first child, cardiovascular disease and oestrogen use gave an RR for breast cancer of 1.97 (95% CI 1.29-3.00). The 95% CIs crossed 1.0 for the RR calculated in all analyses of users of insulin glargine in combination with other types of insulin.. In Sweden, during 2006 and 2007, women using insulin glargine alone (no other types of insulin) had an increased incidence rate of breast cancer as compared with women using types of insulin other than insulin glargine. This result may be due to a random fluctuation; the possibilities for examining validity are limited, and no statistically significant results were obtained for any other individual cancer site or for the outcome 'all malignancies'. No definitive conclusions regarding a possible causal relationship between insulin glargine use and the occurrence of malignancies can be drawn from the results of this study.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Breast Neoplasms; Cardiovascular Diseases; Diabetes Complications; Diabetic Angiopathies; Educational Status; Female; Follow-Up Studies; Gastrointestinal Neoplasms; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Neoplasms; Prostatic Neoplasms; Registries; Smoking; Sweden

Topics: Carcinogens; Diabetes Complications; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Patient Selection; Reproducibility of Results; Research Design

The aim of the present study was to examine whether patients with diabetes in Scotland using insulin glargine have a greater cancer risk than patients using other types of insulin.. We used a nationwide diabetes clinical database that covers the majority of the Scottish population with diagnosed diabetes, and examined patients with diabetes who were exposed to any insulin therapy between 1 January 2002 and 31 December 2005. Among these we defined a fixed cohort based on exposure during a 4 month period in 2003 (n = 36,254, in whom 715 cases of cancer occurred) and a cohort of new insulin users across the period (n = 12,852 in whom 381 cancers occurred). Records from these cohorts were linked to cancer registry data up to the end of 2005. We used Cox proportional hazards models for survival analyses.. Those receiving any insulin glargine (n = 3,959) had the same incidence rate for all cancers as those not receiving insulin glargine (HR 1.02, 95% CI 0.77-1.36, p = 0.9 in the fixed cohort) The subset of patients using insulin glargine alone (n = 447) had a significantly higher incidence of all cancers than those using other insulins only (n = 32,295) (HR 1.55, 95% CI 1.01-2.37, p = 0.045), and those using insulin glargine with other insulins (n = 3,512) had a slightly lower incidence (HR 0.81, 95% CI 0.55-1.18, p = 0.26). There were important differences in baseline characteristics between these three groups, although the risk ratios were broadly unaltered on adjustment for these. Overall, there was no increase in breast cancer rates associated with insulin glargine use (HR 1.49, 95% CI 0.79-2.83, though insulin glargine only users had a higher rate than those using non-glargine insulin only (HR 3.39, 95% CI 1.46-7.85, p = 0.004). Among type 2 diabetic incident insulin users, no significant difference between the three groups was observed with respect to all cancer or breast cancer. All the above HRs are adjusted for age, calendar time prior cancer and type of diabetes, as appropriate, and are stratified according to sex.. Overall, insulin glargine use was not associated with an increased risk of all cancers or site-specific cancers in Scotland over a 4 year time frame. Given the overall data, we consider the excess of cases of all cancers and breast cancer in the subgroup of insulin glargine only users to more likely reflect allocation bias rather than an effect of insulin glargine itself.

Topics: Breast Neoplasms; Chromosome Mapping; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Neoplasms; Probability; Registries; Retrospective Studies; Scotland; Survival Analysis

Topics: Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Proportional Hazards Models; Research Design; Survival Analysis

Topics: Evidence-Based Practice; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Mitogens; Neoplasms; Peer Review, Research; Research Design; Risk Factors

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk Factors

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Randomized Controlled Trials as Topic; Risk

Topics: Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Registries; Risk

Topics: Bias; Breast Neoplasms; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Neoplasms; Risk

Topics: Bias; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Patient Education as Topic; Retrospective Studies; Risk

Topics: Bias; Clinical Trials as Topic; Conflict of Interest; Delayed-Action Preparations; Diabetes Mellitus; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Patient Education as Topic; Risk

Recent publications of data extracted from population registries have suggested a possible relationship between treatment with insulin glargine and increased incidence of cancer/breast cancer. The aim of the present study was investigate this possible relationship using data from the manufacturer's (sanofi-aventis) pharmacovigilance database.. We analysed the manufacturer's (sanofi-aventis) pharmacovigilance database for all randomised clinical trials (RCTs; Phase 2-4) comparing insulin glargine with any comparator in type 1 or type 2 diabetes. We identified all serious adverse events coded under the System Organ Class of 'neoplasms, benign, malignant and unspecified'. Treatment-emergent neoplasms judged to be malignant were included in this analysis.. The database included 31 studies, 12 in type 1 diabetes and 19 in type 2 diabetes. Twenty compared insulin glargine with NPH insulin, 29 were parallel-group studies and two had a crossover design. Studies were generally of 6 months' duration, except for trial reference number 4016 (n = 1,017), which had a duration of 5 years. Overall, 10,880 people were included in the analysis (insulin glargine, 5,657; comparator, 5,223). Forty-five people (0.8%) vs 46 people (0.9%) reported 52 and 48 cases of malignant cancer in the insulin glargine and comparator groups, respectively (RR 0.90, 95% CI 0.60-1.36). Skin (12 people with 16 events vs six people with seven events, RR 1.85, 95% CI 0.69-4.92), colon and rectum (six vs ten people, RR 0.55, 95% CI 0.20-1.52), breast (four vs six people, RR 0.62, 95% CI 0.17-2.18) and gastrointestinal tract (six vs four people, RR 1.38, 95% CI 0.39-4.90) were the most commonly reported sites.. In these 31 RCTs, insulin glargine was not associated with an increased incidence of cancer, including breast cancer, compared with the comparator group.

Topics: Adolescent; Adult; Child; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Random Allocation; Randomized Controlled Trials as Topic

Topics: Diabetes Mellitus; Editorial Policies; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Periodicals as Topic; Risk Factors

Topics: Diabetes Mellitus; Humans; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Neoplasms; Obesity

Topics: Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Mass Media; Neoplasms; Risk Assessment

Insulin glargine is widely used as basal insulin in the treatment of type 1 and type 2 diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk of cancer, especially breast cancer, in patients with type 2 diabetes. The present article aims at briefly presenting the state of the art based upon currently available data. We will first summarize the observations reported in recent publications, then we will present a critical analysis of these in fact non-conclusive findings, and finally we will conclude with some practical recommendations.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Prospective Studies; Risk Assessment

Topics: Humans; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk Factors

Topics: Databases, Factual; Diabetes Complications; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Neoplasms

We wanted to assess the effectiveness and safety of glargine in the treatment of patients with type 2 diabetes mellitus in secondary failure and/or with severe comorbidities ("T2DM group"), and patients with secondary diabetes after corticosteroid and/or anticancer treatment ("secondary DM group"). We reviewed the records of patients on glargine from 1 August 2004 to 30 July 2005. The after-minus-before change in HbA1c was the main outcome measure. At baseline, the 18 "T2DM" patients had a mean (+/-SD) age of 66.7+/-9.5 years and a diabetes duration of 13.6+/-10.3 years; 52.9% were male. Their fasting plasma glucose (FPG) decreased from 228.6+/-76.6 to 134.6+/-37.5, two-hour post-prandial glycaemia (2hPPG) from 268.2+/-10.4 to 140.6+/-30.8 and HbA1c from 10.4+/-2.3 to 7.9+/-1.6%. Mean daily insulin dosage was 12.0+/-4.8 UI for glargine alone and 37.4+/-22.6 UI for basal-bolus scheme. The daily cost was Euro 0.75 (range Euro 0.31-1.15). The 24 "secondary DM" patients had a mean age of 67.0+/-11.0 years and a diabetes duration of 3.7+/-6.5 years; 54.2% were male and 91.7% had a metastatic cancer. Their FPG decreased from 222.3+/-108.6 to 121.5+/-28.7 mg/dl, 2hPPG from 259.4+/-108.6 to 133.0+/-35.0 mg/dl and HbA1c from 10.1+/-2.5 to 7.6+/-1.3%. Mean daily insulin dosage was 12.5+/-6.1 UI for glargine alone and 27.2+/-9.1 UI for basal-bolus scheme. Mean daily cost was Euro 0.70 (range Euro 0.31-1.38). One (4.2%) cancer patient withdrew from glargine because of nausea. Nine (37.5%) cancer patients had an increase in appetite after glargine therapy, including 3 end-of-life patients. No severe hypoglycaemia occurred. Insulin glargine was safe and effective in improving glycaemic control both in severe "T2DM" and in "secondary DM" patients.

Topics: Adrenal Cortex Hormones; Aged; Antineoplastic Agents; Blood Glucose; Body Mass Index; Body Weight; Cardiovascular Diseases; Comorbidity; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Renal Insufficiency; Retrospective Studies; Treatment Outcome

Topics: Animals; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Neoplasms; Rats