The Body Weight Alteration and Incidence of Neoplasm in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Abstract

Objective: Whether 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 methods: Systematic 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.

Results: In 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.

Conclusions: Additional 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.

Keywords: body-weight trajectory; cancer; hypoglycemic agents; neoplasms; type 2 diabetes.

Figure 1

Flow diagram of the included studies.

Figure 2

Weight alteration and incidence of neoplasm in randomized clinical trials of patients with type 2 diabetes. (A) Randomized controlled trials with weight reduction difference. CANA, canagliflozin; DAPA, dapagliflozin; EMPA, empagliflozin; ERTU, ertugliflozin; SAXA, saxagliptin; SITA, sitagliptin; GLP-1RA, glucagon-like peptide-1 receptor agonist; ALBI, albiglutide; DPP-4i, dipeptidyl-peptidase-4 inhibitors; MET, metformin; PIO, pioglitazone; PBO, placebo; CANVAS, Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes; CANVAS-R, CANVAS-Renal; CREDENCE, Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy; DECLARE-TIMI 58, The Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction; CAROLINA, Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes; EMPA-REG, Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes; HARMONY, Albiglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease; REWIND, Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes; LEADER: Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes; SUSTAIN6, Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes; ELIXA, Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome; DUAL VIII, Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes. (B) Randomized controlled trials with weight elevation difference. SU, sulfonylurea; TZD, thiazolidinedione; VADT, Veterans Affairs Diabetes Trial; ACCORD, The Action to Control Cardiovascular Risk in Diabetes; UKPDS, The UK Prospective Diabetes Study; RECORD, Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes.

Figure 3

Meta-regression analysis of weight change difference and change rate with incidence of neoplasm in patients with type 2 diabetes. (A) Weight change difference and incidence of neoplasm (β = −0.030, 95% CI, −0.068 to 0.007, P = 0.115). (B) Weight change rate and incidence of neoplasm (β = −5.983, 95% CI, −11.412 to 0.553, P = 0.031).

Figure 4

The association between weight reduction difference or change rate and the incidence of uterine neoplasm. (A) Weight reduction difference and incidence of uterine neoplasm (β = 0.8743, 95% CI, 0.2206 to 1.5280, P = 0.012). (B) Weight reduction rate and incidence of uterine neoplasm (β = 34.062, 95% CI, −6.3617 to 74.4857, P = 0.094).