Article type
Abstract
Background
Individuals with type 2 diabetes often experience compromised bone health, leading to a higher likelihood of fractures. While pharmacological treatment is crucial for managing diabetes-related complications, its impact on bone integrity remains uncertain.
Objectives
This study aims to evaluate the time-dependent fracture risk in adults with type 2 diabetes who are receiving different anti-diabetic medications.
Methods
A comprehensive search of MEDLINE, EMBASE, and the Cochrane Library was conducted up to November 18, 2021, to identify randomized controlled trials (RCTs) and propensity-score-matched non-randomized studies (NRSs) comparing the effects of various anti-diabetic drugs with standard treatments or with each other in relation to fracture risk among adults with type 2 diabetes. A one-stage network meta-analysis was carried out using discrete-time hazard regression, which utilized reconstructed individual time-to-event data.
Results
The network meta-analysis (NMA) included seven RCTs involving 65,051 adults with type 2 diabetes (median follow-up: 36 months) and three propensity-score-based NRSs with 17,954 participants (median follow-up: 27.3 months). The findings indicate that thiazolidinediones increased the overall fracture risk by 42% (95% credible interval [CrI]: 3%-97%), with the hazard nearly tripling after four years (hazard ratio [HR]: 2.74; 95% CrI: 1.53-4.80). Subgroup analysis suggested that this increased risk was significant among females (HR: 2.19; 95% CrI: 1.26-3.74) but not among males (HR: 0.81; 95% CrI: 0.45-1.40). Moderate certainty evidence suggests that thiazolidinediones could result in 92 additional fractures over five years per 1,000 female patients. No significant fracture risk was found with other anti-diabetic drugs, including metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors.
Conclusions
Long-term use of thiazolidinediones is linked to a heightened fracture risk in female patients with type 2 diabetes, while no similar risk was observed with other anti-diabetic medications.
Individuals with type 2 diabetes often experience compromised bone health, leading to a higher likelihood of fractures. While pharmacological treatment is crucial for managing diabetes-related complications, its impact on bone integrity remains uncertain.
Objectives
This study aims to evaluate the time-dependent fracture risk in adults with type 2 diabetes who are receiving different anti-diabetic medications.
Methods
A comprehensive search of MEDLINE, EMBASE, and the Cochrane Library was conducted up to November 18, 2021, to identify randomized controlled trials (RCTs) and propensity-score-matched non-randomized studies (NRSs) comparing the effects of various anti-diabetic drugs with standard treatments or with each other in relation to fracture risk among adults with type 2 diabetes. A one-stage network meta-analysis was carried out using discrete-time hazard regression, which utilized reconstructed individual time-to-event data.
Results
The network meta-analysis (NMA) included seven RCTs involving 65,051 adults with type 2 diabetes (median follow-up: 36 months) and three propensity-score-based NRSs with 17,954 participants (median follow-up: 27.3 months). The findings indicate that thiazolidinediones increased the overall fracture risk by 42% (95% credible interval [CrI]: 3%-97%), with the hazard nearly tripling after four years (hazard ratio [HR]: 2.74; 95% CrI: 1.53-4.80). Subgroup analysis suggested that this increased risk was significant among females (HR: 2.19; 95% CrI: 1.26-3.74) but not among males (HR: 0.81; 95% CrI: 0.45-1.40). Moderate certainty evidence suggests that thiazolidinediones could result in 92 additional fractures over five years per 1,000 female patients. No significant fracture risk was found with other anti-diabetic drugs, including metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors.
Conclusions
Long-term use of thiazolidinediones is linked to a heightened fracture risk in female patients with type 2 diabetes, while no similar risk was observed with other anti-diabetic medications.