Abstract

ObjectiveWhether hypoglycemic treatments with weight-alternating effects influence the incidence of neoplasm in type 2 diasbetes (T2D) remains uncertain. Therefore, we performed a meta-analysis to assess the association between the weight alteration and incidence of neoplasm in patients with T2D.Research Design and MethodsSystematic searches were conducted for studies published between the inception of 1950s and September 2019. Randomized controlled trials conducted in T2D patients with at least 48-week follow-up, significant weight change difference between treatment arms and reports of neoplasm events were included. Fixed-effects model and meta-regression analysis were accordingly used.ResultsIn all, 46 studies were included. Analysis indicated weight reduction was not associated with a decreased incidence of neoplasm (OR = 1.01, 95% CI, 0.96 to 1.07, I2 = 17%) and weight elevation was not associated with an increased incidence of neoplasm (OR = 0.91, 95% CI, 0.76 to 1.09, I2 = 0%). Meta-regression analysis showed a slower weight reduction rate (β = −5.983, 95% CI, −11.412 to 0.553, P = 0.03) instead of weight change difference (β = −0.030, 95% CI, −0.068 to 0.007, P = 0.115) was significantly associated with reduced risk of neoplasm in patients with T2D. Moreover, a decreased incidence of prostate, bladder, and uterine neoplasm was observed in T2D patients with weight reduction difference while an increased incidence of thyroid neoplasm was found in glucagon-like peptide-1 receptor analog (GLP-1RA) users with weight reduction difference.ConclusionsAdditional weight change achieved by current hypoglycemic agents or strategies in short and medium periods was not associated with incidence of most neoplasm in patients with T2D. However, a decreased incidence of prostate, bladder, and uterine neoplasm was shown in T2D patients with weight reduction difference while an increased risk of thyroid neoplasm was observed in T2D patients on GLP-1RA treatments with weight reduction difference. A more sustained and persistent weight reduction process may confer reduced risk of neoplasm in patients with T2D.

Highlights

  • Type 2 diabetes (T2D) and cancer are two common noncommunicable diseases with increasing prevalence all over the world [1]

  • After comprehensive literature search and selection, 46 eligible randomized controlled trial (RCT) with 69061 participants in the experimental group and 59431 participants in the control group were included in this metaanalysis (Figure 1)

  • For RCTs with weight reduction difference, only two RCTs were with long period follow up, seven RCTs with medium periods while the rest 34 belonged to short period classification

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Summary

Introduction

Type 2 diabetes (T2D) and cancer are two common noncommunicable diseases with increasing prevalence all over the world [1]. The increased incidence of cancer in patients with T2D has been reported in many epidemiological studies [2,3,4]. A pooled analysis of cohort study enrolling 771,000 individuals in Asia indicated baseline diabetes status was significantly associated with an increased risk of death from any cancer. Obesity is recognized as one of the Abbreviations: T2D, type 2 diabetes; SGLT2i, sodium glucose cotransporter 2 inhibitor; GLP-1RA, glucagon-like peptide-1 receptor analog; RCT, randomized controlled trial; TZD, thiazolidinedione; SU, sulfonylurea; CVOT, cardiovascular outcome trials; ROT, renal outcome trials; WMD, weighted mean difference; CI, confidence interval; RR, relative risk; OR, odds ratio; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; HARMONY, Albiglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease; CAROLINA, Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes; BMI, body mass index; IARC, the International Agency for Research on Cancer; ERK, extracellular signal–regulated kinase; MAPK, mitogen-activated protein kinase; lookADEAD, Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes; TODAY, Treatment Options for Type 2 Diabetes in Adolescents and Youth; TECOS, Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes; CARMELINA, The Cardiovascular and Renal Microvascular Outcome Study with Linagliptin; ORIGIN, Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

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