Comparative effectiveness of gliclazide modified-release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes
Sulfonylureas (SUs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are available for second-line treatment after metformin in type 2 diabetes mellitus (T2D). Gliclazide modified release (MR) (SUs) and Sitagliptin (DPP-4) are being used commonly. To compare the effectiveness of these two drugs, Zaccardi and colleagues (2020) published a study titled “Comparative effectiveness of gliclazide modified-release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes” published in “A Journal of Pharmacology and Therapeutics”. Summary of the findings is being given below:
Objective:
To study the comparison between Gliclazide MR and Sitagliptin as T2D treatment in real-world patients
Method:
Data from the UK Clinical Practice Research Datalink (CPRD Gold) database, that were linked to the Hospital Episode Statistics Admitted Patient Care (HES APC) were used for this cohort study. Data from the Office for National Statistics (ONS) Death Registration databases were used to determine the characteristic of patients and effectiveness.
Adult patient included in the cohort if glycated haemoglobin (hbA1c) is >7% if they were newly started with gliclazide MR or sitagliptin as second-line treatment with metformin. The primary outcome includes hbA1c <7%. Time to reach hbA1c <6.5 %, time to >1% hbA1c reduction as compared to baseline, treatment persistency and durability, hypoglycemic events were the secondary outcome.
Using high-dimensional propensity score (HD-PS) matching patients were matched in 1:1 ratio.
Findings:
In real-world patients, treatment with gliclazide MR has shown a greater possibility to achieve hbA1c <7% and <6.5%. This achievement was found evident within 3 months of treatment. This reduction is notable as international guidelines related to better glycemic control with the prevention of long-term risk complication in diabetics. The study reports >2.5 years of comparable median durability and persistency for gliclazide MR and sitagliptin by using HD-PS matching. SUs is believed to have a higher risk of hypoglycemic effects as compare to DPP-4. While this can be true for other SUs, it’s not for gliclazide MR. Gliclazide MR has a lower risk of hypoglycemia. This can be key information in clinical decision making for second-line treatment of T2D.
Limitations:
Authors reports’ that there may be variation in data entry and measurement used as a baseline for HD-PS matching as data from all centres of CPRD were not standardized for the quality outcome and other covariates. Additionally, for participants using metformin background information were not collected. Weight and body mass index were not analyzed as these data were not recorded over time in study. There was a lack of reports for severe events as HES APC reports an only severe event that results in hospitalization. Lastly, in this study medication adherence was not directly measured.
Authors acknowledge future investigation on the dose and other safety outcomes. Patients weight should be included in future studies to investigate the overall risk-benefit profile of gliclazide MR medications.
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