Dataset Information

Differential Effects of Thiazolidinediones and Dipeptidyl Peptidase-4 Inhibitors on Insulin Resistance and β-Cell Function in Type 2 Diabetes Mellitus: A Propensity Score-Matched Analysis.

ABSTRACT:

Introduction

Comparisons of the glycemic durability between thiazolidinediones (TZDs) and dipeptidyl peptidase-4 (DPP-4) inhibitors remain insufficient. This study aimed to find clues for the differences in glycemic durability between TZDs and DPP-4 inhibitors by comparing the insulin resistance and β-cell function among patients using these agents.

Methods

A total of 241 patients with type 2 diabetes mellitus (T2DM) treated with either pioglitazone (a TZD) or DPP-4 inhibitors as combination therapy with metformin for at least 1 year were analyzed. A propensity score based on the patients' baseline characteristics and glycated hemoglobin (HbA1c) was used to match them. Indices for insulin resistance and secretory function of β-cells, namely the homeostasis model assessment of insulin resistance (HOMA-IR) or β-cells (HOMA-β), were calculated and compared. Multiple regression analysis was performed to find the independent variables correlated with β-cell function or insulin resistance.

Results

Evaluation of the data from 168 matched patients with T2DM showed that TZD users had significantly better insulin sensitivity compared with DPP-4 inhibitor users (HOMA-IR 2.3 ± 1.9 vs. 3.5 ± 3.2, p = 0.003). Conversely, DPP-4 inhibitor users secreted more insulin than TZD users (HOMA-β 45.7 ± 31.6 vs. 61.4 ± 49.5, p = 0.016). Multiple linear regression analysis showed that these agents were independently associated with both insulin resistance and β-cell function.

Conclusion

TZD users showed significantly better insulin sensitivity, whereas DPP-4 inhibitor users secreted more insulin from β-cells under similar glycemic control.

SUBMITTER: Bae J

PROVIDER: S-EPMC6349276 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset cognitive dysfunction in type 2 diabetes mellitus remain unknown. This study aimed to evaluate the effects of the two novel antidiabetic agents on cognitive dysfunction by comparing the rates of dementia between SGLT2I and DPP4I users. Methods: This was a population-based cohort study of type 2 diabetes mellitus patients treated with SGLT2I and DPP4I between January 1, 2015 and December 31, 2019 in Hong Kong. Exclusion criteria were <1-month exposure or exposure to both medication classes, or prior diagnosis of dementia or major neurological/psychiatric diseases. Primary outcomes were new-onset dementia, Alzheimer's, and Parkinson's. Secondary outcomes were all-cause, cardiovascular, and cerebrovascular mortality. Results: A total of 13,276 SGLT2I and 36,544 DPP4I users (total n = 51,460; median age: 66.3 years old [interquartile range (IQR): 58-76], 55.65% men) were studied (follow-up: 472 [120-792] days). After 1:2 matching (SGLT2I: n = 13,283; DPP4I: n = 26,545), SGLT2I users had lower incidences of dementia (0.19 vs. 0.78%, p < 0.0001), Alzheimer's (0.01 vs. 0.1%, p = 0.0047), Parkinson's disease (0.02 vs. 0.14%, p = 0.0006), all-cause (5.48 vs. 12.69%, p < 0.0001), cerebrovascular (0.88 vs. 3.88%, p < 0.0001), and cardiovascular mortality (0.49 vs. 3.75%, p < 0.0001). Cox regression showed that SGLT2I use was associated with lower risks of dementia (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: [0.27-0.61], P < 0.0001), Parkinson's (HR:0.28, 95% CI: [0.09-0.91], P = 0.0349), all-cause (HR:0.84, 95% CI: [0.77-0.91], P < 0.0001), cardiovascular (HR:0.64, 95% CI: [0.49-0.85], P = 0.0017), and cerebrovascular (HR:0.36, 95% CI: [0.3-0.43], P < 0.0001) mortality. Conclusions: The use of SGLT2I is associated with lower risks of dementia, Parkinson's disease, and cerebrovascular mortality compared with DPP4I use after 1:2 ratio propensity score matching.