Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis

Background. Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects...

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Main Authors: Abraham Nigussie Mekuria, Yohanes Ayele, Assefa Tola, Kirubel Minsamo Mishore
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2019/7676909
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author Abraham Nigussie Mekuria
Yohanes Ayele
Assefa Tola
Kirubel Minsamo Mishore
author_facet Abraham Nigussie Mekuria
Yohanes Ayele
Assefa Tola
Kirubel Minsamo Mishore
author_sort Abraham Nigussie Mekuria
collection DOAJ
description Background. Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus. Objective. A systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients. Methods. Search was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018. In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting. Heterogeneity among the studies was evaluated using I2 statistics. Publication bias was evaluated using the funnel plot asymmetry test. The Newcastle-Ottawa scale (NOS) was used to assess the study quality. Results. A total of 8 cohort studies were included in the meta-analysis. Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR=0.74, 95% CI: 0.55-0.99, I2=97.89%, p<0.00001; adjusted RR=0.76, 95% CI: 0.54–1.07, I2=98.12%, p<0.00001) compared with monotherapy with sulfonylurea, using the random-effects model with inverse-variance weighting. Conclusions. According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes. This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.
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spelling doaj-art-b274e2c5f5c642e5b12d01f3fe6546bf2025-08-20T02:23:12ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/76769097676909Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-AnalysisAbraham Nigussie Mekuria0Yohanes Ayele1Assefa Tola2Kirubel Minsamo Mishore3Department of Pharmacology, College of Health and Medical Sciences, Haramaya University, Harar, EthiopiaDepartment of Clinical Pharmacy, College of Health and Medical Sciences, Haramaya University, Harar, EthiopiaDepartment of Epidemiology and Biostatistics, College of Health and Medical Sciences, Haramaya University, Harar, EthiopiaDepartment of Clinical Pharmacy, College of Health and Medical Sciences, Haramaya University, Harar, EthiopiaBackground. Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus. Objective. A systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients. Methods. Search was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018. In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting. Heterogeneity among the studies was evaluated using I2 statistics. Publication bias was evaluated using the funnel plot asymmetry test. The Newcastle-Ottawa scale (NOS) was used to assess the study quality. Results. A total of 8 cohort studies were included in the meta-analysis. Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR=0.74, 95% CI: 0.55-0.99, I2=97.89%, p<0.00001; adjusted RR=0.76, 95% CI: 0.54–1.07, I2=98.12%, p<0.00001) compared with monotherapy with sulfonylurea, using the random-effects model with inverse-variance weighting. Conclusions. According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes. This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.http://dx.doi.org/10.1155/2019/7676909
spellingShingle Abraham Nigussie Mekuria
Yohanes Ayele
Assefa Tola
Kirubel Minsamo Mishore
Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis
Journal of Diabetes Research
title Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis
title_full Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis
title_fullStr Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis
title_full_unstemmed Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis
title_short Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis
title_sort monotherapy with metformin versus sulfonylureas and risk of cancer in type 2 diabetic patients a systematic review and meta analysis
url http://dx.doi.org/10.1155/2019/7676909
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